Abstract
Hypertension is the most prevalent cause of cardiovascular disease and kidney failure, but only about 50% of patients achieve adequate blood pressure control, in part, due to inter-individual genetic variations in the response to antihypertensive medication. Significant strides have been made toward the understanding of the role of reactive oxygen species (ROS) in the regulation of the cardiovascular system. However, the role of ROS in human hypertension is still unclear. Polymorphisms of some genes involved in the regulation of ROS production are associated with hypertension, suggesting their potential influence on blood pressure control and response to antihypertensive medication. This review provides an update on the genes associated with the regulation of ROS production in hypertension and discusses the controversies on the use of antioxidants in the treatment of hypertension, including the antioxidant effects of antihypertensive drugs.
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References
Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífková R, Dominiczak AF, et al. Hypertension. Nat Rev Dis Prim. 2018;4:18014.
Muntner P, Carey RM, Gidding S, Jones DW, Taler SJ, Wright JT Jr, et al. Potential U.S. Population Impact of the 2017 ACC/AHA High Blood Pressure Guideline. J Am Coll Cardiol. 2018;71:109–18.
Greenland P, Peterson E. The New 2017 ACC/AHA Guidelines “Up the Pressure” on Diagnosis and Treatment of Hypertension. JAMA. 2017;318:2083–4.
Cooper-DeHoff RM, Johnson JA. Hypertension pharmacogenomics: in search of personalized treatment approaches. Nat Rev Nephrol. 2016;12:110–22.
Armando I, Villar VA, Jose PA. Genomics and pharmacogenomics of salt-sensitive hypertension. Curr Hypertens Rev. 2015;11:49–56.
Holterman CE, Thibodeau JF, Kennedy CR. NADPH oxidase 5 and renal disease. Curr Opin Nephrol Hypertens. 2015;24:81–87.
Weidinger A, Kozlov AV. Biological activities of reactive oxygen and nitrogen species: oxidative stress versus signal transduction. Biomolecules. 2015;15:472–84.
Loperena R, Harrison DG. Oxidative stress and hypertensive diseases. Med Clin N Am. 2017;101:169–93.
Wilcox CS. Asymmetric dimethylarginine and reactive oxygen species: unwelcome twin visitors to the cardiovascular and kidney disease tables. Hypertension. 2012;59:375–81.
Sorriento D, De Luca N, Trimarco B, Iaccarino G. The antioxidant therapy: new insights in the treatment of hypertension. Front Physiol. 2018;9:258.
Roberts JM, Myatt L, Spong CY, Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, et al. Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med. 2010;362:1282–91.
Montezano AC, Dulak-Lis M, Tsiropoulou S, Harvey A, Briones AM, Touyz RM. Oxidative stress and human hypertension: vascular mechanisms, biomarkers, and novel therapies. Can J Cardiol. 2015;31:631–41.
Brown DI, Griendling KK. Regulation of signal transduction by reactive oxygen species in the cardiovascular system. Circ Res. 2015;116:531–49.
Ma R, Chaudhari S, Li W. Canonical transient receptor potential 6 channel: a new target of reactive oxygen species in renal physiology and pathology. Antioxid Redox Signal. 2016;25:732–48.
Ratliff BB, Abdulmahdi W, Pawar R, Wolin MS. Oxidant mechanisms in renal injury and disease. Antioxid Redox Signal. 2016;25:119–46.
Banday AA, Lokhandwala MF. Transcriptional regulation of renal dopamine D1 receptor function during oxidative stress. Hypertension. 2015;65:1064–72.
Yan Y, Shapiro AP, Haller S, Katragadda V, Liu L, Tian J, et al. Involvement of reactive oxygen species in a feed-forward mechanism of Na/K-ATPase-mediated signaling transduction. J Biol Chem. 2013;288:34249–58.
Lu X, Wang F, Liu M, Yang KT, Nau A, Kohan DE, et al. Activation of ENaC in collecting duct cells by prorenin and its receptor PRR: involvement of Nox4-derived hydrogen peroxide. Am J Physiol Ren Physiol. 2016;310:F1243–50.
Silva-Islas CA, Maldonado PD. Canonical and non-canonical mechanisms of Nrf2 activation. Pharmacol Res. 2018;134:92–99.
Chung HS, Wang SB, Venkatraman V, Murray CI, Van Eyk JE. Cysteine oxidative posttranslational modifications: emerging regulation in the cardiovascular system. Circ Res. 2013;112:382–92.
Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes. 2003;52:1–8.
Wang D, Chen Y, Chabrashvili T, Aslam S, Borrego Conde LJ, Umans JG, et al. Role of oxidative stress in endothelial dysfunction and enhanced responses to angiotensin II of afferent arterioles from rabbits infused with angiotensin II. J Am Soc Nephrol. 2003;14:2783–9.
Kopkan L, Castillo A, Navar LG, Majid DS. Enhanced superoxide generation modulates renal function in ANG II-induced hypertensive rats. Am J Physiol Ren Physiol. 2006;290:F80–6.
Kaess BM, Rong J, Larson MG, Hamburg NM, Vita JA, Levy D, et al. Aortic stiffness, blood pressure progression, and incident hypertension. JAMA. 2012;308:875–81.
Wu J, Saleh MA, Kirabo A, Itani HA, Montaniel KR, Xiao L, et al. Immune activation caused by vascular oxidation promotes fibrosis and hypertension. J Clin Invest. 2016;126:50–67.
Zucchelli P, Zuccalà A, Mancini E. Hypertension in primary glomerulonephritis without renal insufficiency. Nephrol Dial Transplant. 1989;4:605–10.
Nagase M, Shibata S, Yoshida S, Nagase T, Gotoda T, Fujita T. Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker. Hypertension. 2006;47:1084–93.
Meng S, Cason GW, Gannon AW, Racusen LC, Manning RD Jr. Oxidative stress in Dahl salt-sensitive hypertension. Hypertension. 2003;41:1346–52.
Araujo M, Wilcox CS. Oxidative stress in hypertension: role of the kidney. Antioxid Redox Signal. 2014;20:74–101.
Lerman LO, Nath KA, Rodriguez-Porcel M, et al. Increased oxidative stress in experimental renovascular hypertension. Hypertension. 2001;37:541–6.
Li C, Lin Y, Luo R, Chen S, Wang F, Zheng P, et al. Intrarenal renin–angiotensin system mediates fatty acid-induced ER stress in the kidney. Am J Physiol Ren Physiol. 2016;310:F351–63.
Cuevas S, Villar VA, Jose PA, Armando I. Renal dopamine receptors, oxidative stress, and hypertension. Int J Mol Sci. 2013;14:17553–72.
Rukavina Mikusic NL, Kravetz MC, Kouyoumdzian NM, Della Penna SL, Rosón MI, Fernández BE, et al. Signaling pathways involved in renal oxidative injury: role of the vasoactive peptides and the renal dopaminergic system. J Signal Transduct. 2014;2014:731350.
Stec DE, Juncos LA, Granger JP. Renal intramedullary infusion of tempol normalizes the blood pressure response to intrarenal blockade of heme oxygenase-1 in angiotensin II-dependent hypertension. J Am Soc Hypertens. 2016;10:346–51.
Silva GB, Garvin JL. Angiotensin II-dependent hypertension increases Na transport- related oxygen consumption by the thick ascending limb. Hypertension. 2008;52:1091–8.
Luo H, Wang X, Chen C, Wang J, Zou X, Li C, et al. Oxidative stress causes imbalance of renal renin angiotensin system (RAS) components and hypertension in obese Zucker rats. J Am Heart Assoc. 2015;4:e001559.
Ramkumar N, Kohan DE. Proximal tubule angiotensinogen modulation of arterial pressure. Curr Opin Nephrol Hypertens. 2013;22:32–36.
Labandeira-Garcia JL, Rodriguez-Pallares J, Villar-Cheda B, Rodríguez-Perez AI, Garrido-Gil P, Guerra MJ. Aging, Angiotensin system and dopaminergic degeneration in the substantia nigra. Aging Dis. 2011;2:257–74.
Escano CS, Armando I, Wang X, Asico LD, Pascua A, Yang Y, et al. Renal dopaminergic defect in C57Bl/6J mice. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1660–9.
Chugh G, Lokhandwala MF, Asghar M. Altered functioning of both renal dopamine D1 and angiotensin II type 1 receptors causes hypertension in old rats. Hypertension. 2012;59:1029–36.
Ortiz PA, Garvin JL. Superoxide stimulates NaCl absorption by the thick ascending limb. Am J Physiol Ren Physiol. 2002;283:F957–962.
Persson P, Hansell P, Palm F. NADPH oxidase inhibition reduces tubular sodium transport and improves kidney oxygenation in diabetes. Am J Physiol Regul Integr Comp Physiol. 2012;302:R1443–1449.
Cowley AW Jr, Abe M, Mori T, O'Connor PM, Ohsaki Y, Zheleznova NN. Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension. Am J Physiol Ren Physiol. 2015;308:F179–97.
Simão S, Gomes P, Pinho MJ, Soares-da-Silva P. H2O2 stimulates Cl− /HCO3− exchanger activity through oxidation of thiol groups in immortalized SHR renal proximal tubular epithelial cells. J Cell Biochem. 2011;112:3660–5.
Shah PT, Martin R, Yan Y, Shapiro JI, Liu J. Carbonylation modification regulates Na/K-ATPase signaling and salt sensitivity: a review and a hypothesis. Front Physiol. 2016;7:256.
O’Connor PM, Guha A, Stilphen CA, Sun J, Jin C. Proton channels and renal hypertensive injury: a key piece of the Dahl salt-sensitive rat puzzle? Am J Physiol Regul Integr Comp Physiol. 2016;310:R679–690.
Sun P, Yue P, Wang WH. Angiotensin II stimulates epithelial sodium channels in the cortical collecting duct of the rat kidney. Am J Physiol Ren Physiol. 2012;302:F679–687.
Sedeek M, Nasrallah R, Touyz RM, Hébert RL. NADPH oxidases, reactive oxygen species, and the kidney: friend and foe. J Am Soc Nephrol. 2013;24:1512–8.
Cabral PD, Garvin JL. Luminal flow regulates NO and O2(−) along the nephron. Am J Physiol Ren Physiol. 2011;300:F1047–1053.
Andreoli SP, McAteer JA, Seifert SA, Kempson SA. Oxidant-induced alterations in glucose and phosphate transport in LLC-PK1 cells: mechanisms of injury. Am J Physiol. 1993;265:F377–3784.
Kurella EG, Tyulina OV, Boldyrev AA. Oxidative resistance of Na/K-ATPase. Cell Mol Neurobiol. 1999;19:133–40.
Panico C, Luo Z, Damiano S, Artigiano F, Gill P, Welch WJ. Renal proximal tubular reabsorption is reduced in adult spontaneously hypertensive rats: roles of superoxide and Na+/H+exchanger 3. Hypertension. 2009;54:1291–7.
Richards SL, Wilkins KA, Swarbreck SM, Anderson AA, Habib N, Smith AG, et al.The hydroxyl radical in plants: from seed to seed. J Exp Bot. 2015;66:37–46.
Nikinmaa M, Bogdanova A, Lecklin T. Oxygen dependency of the adrenergic Na/H exchange in rainbow trout erythrocytes is diminished by a hydroxyl radical scavenger. Acta Physiol Scand. 2003;178:149–54.
Massey KJ, Hong NJ, Garvin JL. Angiotensin II stimulates superoxide production in the thick ascending limb by activating NOX4. Am J Physiol Cell Physiol. 2012;303:C781–789.
Kopkan L, Cervenka L. Renal interactions of renin–angiotensin system, nitric oxide and superoxide anion: implications in the pathophysiology of salt-sensitivity and hypertension. Physiol Res. 2009;58:S55–67.
Crajoinas RO, Lessa LM, Carraro-Lacroix LR, Davel AP, Pacheco BP, Rossoni LV, et al. Posttranslational mechanisms associated with reduced NHE3 activity in adult vs. young prehypertensive SHR. Am J Physiol Ren Physiol. 2010;299:F872–81.
Boer PA, Morelli JM, Figueiredo JF, Gontijo JA. Early altered renal sodium handling determined by lithium clearance in spontaneously hypertensive rats (SHR): role of renal nerves. Life Sci. 2005;76:1805–15.
Pinto V, Pinho MJ, Hopfer U, Jose PA, Soares-da-Silva P. Oxidative stress and the genomic regulation of aldosterone-stimulated NHE1 activity in SHR renal proximal tubular cells. Mol Cell Biochem. 2008;310:191–201.
Huang WH, Wang Y, Askari A. (Na++K+)-ATPase: inactivation and degradation induced by oxygen radicals. Int J Biochem. 1992;24:621–6.
Banday AA, Lokhandwala MF. Transcription factor Nrf2 protects renal dopamine D1 receptor function during oxidative stress. Hypertension. 2013;62:512–7.
Zou L, Linck V, Zhai YJ, Galarza-Paez L, Li L, Yue Q, et al. Knockout of mitochondrial voltage-dependent anion channel type 3 increases reactive oxygen species (ROS) levels and alters renal sodium transport. J Biol Chem. 2018;293:1666–75.
Chugh G, Lokhandwala MF, Asghar M. Oxidative stress alters renal D1 and AT1 receptor functions and increases blood pressure in old rats. Am J Physiol Ren Physiol. 2011;300:F133–138.
Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J. 1996;10:709–20.
Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114:1752–61.
Thayer TC, Delano M, Liu C, Chen J, Padgett LE, Tse HM, et al. Superoxide production by macrophages and T cells is critical for the induction of autoreactivity and type 1 diabetes. Diabetes. 2011;60:2144–51.
Cachofeiro V, Goicochea M, de Vinuesa SG, Oubiña P, Lahera V, Luño J. Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int Suppl. 2008;111:S4–9.
Manning AM, Bell FP, Rosenbloom CL, Chosay JG, Simmons CA, Northrup JL, et al. NF-kappa B is activated during acute inflammation in vivo in association with elevated endothelial cell adhesion molecule gene expression and leukocyte recruitment. J Inflamm. 1995;45:283–96.
Theuer J, Dechend R, Muller DN, Park JK, Fiebeler A, Barta P, et al. Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats. BMC Cardiovasc Disord. 2002;2:3.
Nishi EE, Oliveira-Sales EB, Bergamaschi CT, Oliveira TG, Boim MA, Campos RR. Chronic antioxidant treatment improves arterial renovascular hypertension and oxidative stress markers in the kidney in Wistar rats. Am J Hypertens. 2010;23:473–80.
Hurr C, Young CN. Neural control of non-vasomotor organs in hypertension. Curr Hypertens Rep. 2016;18:30.
Yang S, Gao Y, Liu G, Li J, Shi K, Du B, et al. The human ATF1rs11169571 polymorphism increases essential hypertension risk through modifying miRNA binding. FEBS Lett. 2015;589:2087–93.
Zhang L, Miyaki K, Araki J, Song Y, Kimura T, Omae K, et al. Interaction of angiotensin I-converting enzyme insertion–deletion polymorphism and daily salt intake influences hypertension in Japanese men. Hypertens Res. 2006;29:751–8.
Todoroki M, Minami J, Ishimitsu T, Ohrui M, Matsuoka H. Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects. J Hum Hypertens. 2003;17:713–8.
Jain S, Vinukonda G, Fiering SN, Kumar A. A haplotype of human angiotensinogen gene containing -217A increases blood pressure in transgenic mice compared with −217G. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1849–1857.
Jain S, Tillinger A, Mopidevi B, Pandey VG, Chauhan CK, Fiering SN, et al. Transgenic mice with −6A haplotype of the human angiotensinogen gene have increased blood pressure compared with −6G haplotype. J Biol Chem. 2010;285:41172–86.
Kayima J, Liang J, Natanzon Y, Nankabirwa J, Ssinabulya I, Nakibuuka J, et al. Association of genetic variation with blood pressure traits among East Africans. Clin Genet. 2017;92:487–94.
Kumar A, Li Y, Patil S, Jain S. A haplotype of the angiotensinogen gene is associated with hypertension in african americans. Clin Exp Pharmacol Physiol. 2005;32:495–502.
Zeng R, Wang QP, Fang MX, Zhuang J, Fan RX. Association of A-20C polymorphism in the angiotensinogen gene with essential hypertension: a meta-analysis. Genet Mol Res. 2015;14:12984–92.
Norat T, Bowman R, Luben R, Welch A, Khaw KT, Wareham N, et al. Blood pressure and interactions between the angiotensin polymorphism AGT M235T and sodium intake: a cross-sectional population study. Am J Clin Nutr. 2008;88:392–7.
Purkait P, Halder K, Thakur S, Ghosh Roy A, Raychaudhuri P, Bhattacharya S, et al. Association of angiotensinogen gene SNPs and haplotypes with risk of hypertension in eastern Indian population. Clin Hypertens. 2017;23:12.
Sethi AA, Nordestgaard BG, Tybjaerg-Hansen A. Angiotensinogen gene polymorphism, plasma angiotensinogen, and risk of hypertension and ischemic heart disease: a meta-analysis. Arterioscler Thromb Vasc Biol. 2003;23:1269–75.
Forman JP, Fisher ND, Pollak MR, Cox DG, Tonna S, Curhan GC. Renin–angiotensin system polymorphisms and risk of hypertension: influence of environmental factors. J Clin Hypertens. 2008;10:459–66.
Sano M, Kuroi N, Nakayama T, Sato N, Izumi Y, Soma M. Association study: the aminopeptidase a gene and essential hypertension. Int J Biomed Sci. 2005;1:16–22.
Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin–angiotensin–aldosterone system alterations. Circ Res. 2015;116:960–75.
Van Haaster MC, McDonough AA, Gurley SB. Blood pressure regulation by the angiotensin type 1 receptor in the proximal tubule. Curr Opin Nephrol Hypertens. 2018;27:1–7.
Cipollone F, Toniato E, Martinotti S, Fazia M, Iezzi A, Cuccurullo C, et al. A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke. JAMA. 2004;291:2221–8.
Martínez-Revelles S, Avendaño MS, García-Redondo AB, Alvarez Y, Aguado A, Pérez-Girón JV, et al. Reciprocal relationship between reactive oxygen species and cyclooxygenase-2 and vascular dysfunction in hypertension. Antioxid Redox Signal. 2013;18:51–65.
Iwai N, Tago N, Yasui N, Kokubo Y, Inamoto N, Tomoike H, et al. Genetic analysis of 22 candidate genes for hypertension in the Japanese population. J Hypertens. 2004;22:1119–26.
Fava C, Ricci M, Melander O, Minuz P. Hypertension, cardiovascular risk and polymorphisms in genes controlling the cytochrome P450 pathway of arachidonic acid: a sex-specific relation? Prostaglandins Other Lipid Mediat. 2012;98:75–85.
Jennings BL, Montanez DE, May ME Jr, Estes AM, Fang XR, Yaghini FA, et al. Cytochrome P450 1B1 contributes to increased blood pressure and cardiovascular and renal dysfunction in spontaneously hypertensive rats. Cardiovasc Drugs Ther. 2014;28:145–61.
Savas Ü, Wei S, Hsu MH, Falck JR, Guengerich FP, Capdevila JH, et al. 20-Hydroxyeicosatetraenoic acid (HETE)-dependent hypertension in human cytochrome P450 (CYP) 4A11 transgenic mice: normalization of blood pressure by sodium restriction, hydrochlorothiazide, or blockade of the type 1 angiotensin II receptOR. J Biol Chem. 2016;291:16904–19.
Jennings BL, Moore JA, Pingili AK, Estes AM, Fang XR, Kanu A, et al. Disruption of the cytochrome P-450 1B1 gene exacerbates renal dysfunction and damage associated with angiotensin II-induced hypertension in female mice. Am J Physiol Ren Physiol. 2015;308:F981–992.
Dennerlein S, Rehling P. Human mitochondrial COX1 assembly into cytochrome c oxidase at a glance. J Cell Sci. 2015;128:833–7.
Polonikov AV, Ivanov VP, Solodilova MA, Khoroshaya IV, Kozhuhov MA, Ivakin VE, et al. A common polymorphism G-50T in cytochrome P450 2J2 gene is associated with increased risk of essential hypertension in a Russian population. Dis Markers. 2008;24:119–26.
King LM, Gainer JV, David GL, Dai D, Goldstein JA, Brown NJ, et al. Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension. Pharm Genom. 2005;15:7–13.
Zhang L, Miyaki K, Wang W, Muramatsu M. CYP3A5 polymorphism and sensitivity of blood pressure to dietary salt in Japanese men. J Hum Hypertens. 2010;24:345–50.
Tzveova R, Naydenova G, Yaneva T, Dimitrov G, Vandeva S, Matrozova Y, et al. Gender-specific effect of CYP2C8*3 on the risk of essential hypertension in Bulgarian patients. Biochem Genet. 2015;53:319–33.
Bochud M, Eap CB, Elston RC, Bovet P, Maillard M, Schild L, et al. Association of CYP3A5 genotypes with blood pressure and renal function in African families. J Hypertens. 2006;24:923–9.
Plenty NL, Faulkner JL, Cotton J, Spencer SK, Wallace K, LaMarca B, et al. Arachidonic acid metabolites of CYP4A and CYP4F are altered in women with preeclampsia. Prostaglandins Other Lipid Mediat. 2018;136:15–22.
Fu Z, Nakayama T, Sato N, Izumi Y, Kasamaki Y, Shindo A, et al. Haplotype of the CYP4A11 gene associated with essential hypertension in Japanese men. J Hypertens. 2008;26:453–61.
Zhang H, Jin L, Mu T, Fan Y, Zhang H, Zhu Y, et al. Associations of CYP4A11 gene–gene and gene–smoking interactions with essential hypertension in the male eastern Chinese Han population. Clin Exp Hypertens. 2017;39:448–53.
Luo H, Wang X, Wang J, Chen C, Wang N, Xu Z, et al. Chronic NF-κB blockade improves renal angiotensin II type 1 receptor functions and reduces blood pressure in Zucker diabetic rats. Cardiovasc Diabetol. 2015;14:76.
Rahman T, Baker M, Hall DH, Avery PJ, Keavney B. Common genetic variation in the type A endothelin-1 receptor is associated with ambulatory blood pressure: a family study. J Hum Hypertens. 2008;22:282–8.
Nikkari ST, Visto AL, Määttä KM, Kunnas TA. Minor variant of rs 16827043 in the iron regulator hemojuvelin gene (HJV) contributes to hypertension: The TAMRISK Study. Medicine (Baltimore, Md). 2017;96:e6052.
Manhiani MM, Seth DM, Banes-Berceli AK, Satou R, Navar LG, Brands MW, et al. The role of IL-6 in the physiologic versus hypertensive blood pressure actions of angiotensin II. Physiol Rep. 2015;3:e12595.
Bayoumy NM, Al-Sharaidh AS, Babay ZH, Abdulgader AM. The role of interleukin-6 promoter polymorphism −174G/C in Saudi women with hypertensive disorders of pregnancy. Saudi Med J. 2013;34:689–94.
Losito A, Kalidas K, Santoni S, Jeffery S. Association of interleukin-6 −174G/C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients. Kidney Int. 2003;64:616–22.
Riikola A, Sipilä K, Kähönen M, Jula A, Nieminen MS, Moilanen L, et al. Interleukin-6 promoter polymorphism and cardiovascular risk factors: the Health 2000 Survey. Atherosclerosis. 2009;207:466–70.
Ma H, Sun G, Wang W, Zhou Y, Liu D, Tong Y, et al. Association between interleukin-6 −572 C>G and −174 G>C polymorphisms and hypertension: a meta-analysis of case–control studies. Medicine (Baltimore, Md). 2016;95:e2416.
Saleh MA, Norlander AE, Madhur MS. Inhibition of interleukin 17-A but not interleukin-17F signaling lowers blood pressure and reduces end-organ inflammation in angiotensin II-induced hypertension. JACC Basic Transl Sci. 2016;1:606–16.
Shuang L, Li Z, Chen F, Cui X, Ning Y, Su Y, et al. Association between interleukin-17 gene polymorphisms and risk of coronary artery disease. Int J Clin Exp Pathol. 2015;8:11653–8.
Lu X, Wang L, Lin X, Huang J, Charles Gu C, He M, et al. Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension Hum Mol Genet. 2015;24:865–74.
Huby AC, Otvos L Jr, Belin de Chantemèle EJ. Leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in obese female mice. Hypertension. 2016;67:1020–1018.
do Carmo JM, da Silva AA, Wang Z, Fang T, Aberdein N, de Lara Rodriguez CE, et al. Obesity-induced hypertension: brain signaling pathways. Curr Hypertens Rep. 2016;18:58.
Li YX, Zhang Q, Shang XM, Li YQ, Liu XK, Liu CQ, et al. Association of two well-defined polymorphisms in leptin and leptin receptor genes with hypertension and circulating leptin: a meta-analysis. Arch Med Res. 2015;46:38–46.
Farias DR, Franco-Sena AB, Rebelo F, Salles GF, Struchiner CJ, Martins MC, et al. Polymorphisms of leptin (G2548A) and leptin receptor (Q223R and K109R) genes and blood pressure during pregnancy and the postpartum period: a cohort. Am J Hypertens. 2017;30:130–40.
Rosmond R, Chagnon YC, Holm G, Chagnon M, Pérusse L, Lindell K, et al. Hypertension in obesity and the leptin receptor gene locus. J Clin Endocrinol Metab. 2000;85:3126–31.
Doi K, Noiri E, Maeda R, Nakao A, Kobayashi S, Tokunaga K, et al. Functional polymorphism of the myeloperoxidase gene in hypertensive nephrosclerosis dialysis patients. Hypertens Res. 2007;30:1193–8.
Liu YC, Chung CJ, Shiue HS, Cheng YY, Huang SR, Su CT, et al. Genetic polymorphisms of myeloperoxidase and their effect on hypertension. Blood Press. 2013;22:282–9.
Fang J, Ma L, Zhang S, Fang Y, Su P, Ma H. Association of myeloperoxidase gene variation with carotid atherosclerosis in patients with essential hypertension. Mol Med Rep. 2013;7:313–7.
Bushueva O, Solodilova M, Ivanov V, Polonikov A. Gender-specific protective effect of the −463G>A polymorphism of myeloperoxidase gene against the risk of essential hypertension in Russians. J Am Soc Hypertens. 2015;9:902–6.
Hasanpour Z, Javanmard SH, Gharaaty M, Sadeghi M. Association between serum myeloperoxidase levels and coronary artery disease in patients without diabetes, hypertension, obesity, and hyperlipidemia. Adv Biomed Res. 2016;5:103.
Nouri P, Gill P, Li M, Wilcox CS, Welch WJ. p22phox in the macula densa regulates single nephron GFR during angiotensin II infusion in rats. Am J Physiol Heart Circ Physiol. 2007;292:H1685–1689.
Modlinger P, Chabrashvili T, Gill PS, Mendonca M, Harrison DG, Griendling KK, et al. RNA silencing in vivo reveals role of p22phox in rat angiotensin slow pressor response. Hypertension. 2006;47:238–44.
Kumar R, Kohli S, Ali Z. CYBA (p22phox) variants associate with blood pressure and oxidative stress markers in hypertension: a replication study in populations of diverse altitudes. Hypertens Res. 2015;38:498–506.
Bedard K, Attar H, Bonnefont J, Jaquet V, Borel C, Plastre O, et al. Three common polymorphisms in the CYBA gene form a haplotype associated with decreased ROS generation. Hum Mutat. 2009;30:1123–33.
Petrovič D. Association of the −262C/T polymorphism in the catalase gene promoter and the C242T polymorphism of the NADPH oxidase P22phox gene with essential arterial hypertension in patients with diabetes mellitus type 2. Clin Exp Hypertens. 2014;36:36–39.
Schreiber R, Bellinazzi VR, Sposito AC, Mill JG, Krieger JE, Pereira AC, et al. Influence of the C242T polymorphism of the p22-phox gene (CYBA) on the interaction between urinary sodium excretion and blood pressure in an urban Brazilian population. PLoS ONE. 2013;8:e81054.
Castejon AM, Bracero J, Hoffmann IS, Alfieri AB, Cubeddu LX. NAD(P)H oxidase p22phox gene C242T polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics. J Hum Hypertens. 2006;20:772–9.
Di Castelnuovo A, Soccio M, Iacoviello L, Evangelista V, Consoli A, Vanuzzo D, et al. The C242T polymorphism of the p22phox component of NAD(P)H oxidase and vascular risk. Two case-control studies and a meta-analysis. Thromb Haemost. 2008;99:594–601.
Sun Q, Yin Y, Zhu Z, Yan Z. Association of the C242T polymorphism in the NAD(P)H oxidase p22 phox gene with type 2 diabetes mellitus risk: a meta-analysis. Curr Med Res Opin. 2014;30:415–22.
Qin YW, Peng J, Liang BY, Su L, Chen Q, Xie JJ, et al. The A930G polymorphism of p22phox (CYBA) gene but not C242T variation is associated with hypertension: a meta-analysis. PLoS ONE. 2013;8:e82465.
Nowak T, Niemiec P, Górczyńska-Kosiorz S, Balcerzyk A, Iwanicki T, Krauze J, et al. The CYBA gene (α) 49A>G polymorphism (rs7195830) is associated with hypertension in patients with coronary artery disease. Biomed Res Int. 2016;2016:1539671.
Moreno MU, San José G, Fortuño A, Beloqui O, Redón J, Chaves FJ, et al. A novel CYBA variant, the −675A/T polymorphism, is associated with essential hypertension. J Hypertens. 2007;25:1620–6.
Niemiec P, Zak I, Emich-Widera E, Balcerzyk A, Kopyta I, Nowak T, et al. The C242T polymorphism of the gene encoding cytochrome b-245 alpha is not associated with paediatric ischaemic stroke: family-based and case–control study. Neurol Neurochir Pol. 2010;44:453–8.
Feairheller DL, Brown MD, Park JY, Brinkley TE, Basu S, Hagberg JM, et al. Exercise training, NADPH oxidase p22phox gene polymorphisms, and hypertension. Med Sci Sports Exerc. 2009;41:1421–8.
Schreiber R, Ferreira-Sae MC, Ronchi JA, Pio-Magalhães JA, Cipolli JA, Matos-Souza JR, et al. The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients. BMC Med Genet. 2011;12:114.
Gavazzi G, Banfi B, Deffert C, Fiette L, Schappi M, Herrmann F, et al. Decreased blood pressure in NOX1-deficient mice. FEBS Lett. 2006;580:497–504.
Sirokmány G, Donkó Á, Geiszt M. Nox/Duox family of NADPH oxidases: lessons from knockout mouse models. Trends Pharmacol Sci. 2016;37:318–27.
Fujii A, Nakano D, Katsuragi M, Ohkita M, Takaoka M, Ohno Y, et al. Role of gp91phox-containing NADPH oxidase in the deoxycorticosterone acetate-salt-induced hypertension. Eur J Pharmacol. 2006;552:131–4.
Haque MZ, Majid DS. High salt intake delayed angiotensin II-induced hypertension in mice with a genetic variant of NADPH oxidase. Am J Hypertens. 2011;24:114–8.
Murdoch CE, Alom-Ruiz SP, Wang M, Zhang M, Walker S, Yu B, et al. Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction. Basic Res Cardiol. 2011;106:527–38.
Zhang A, Jia Z, Wang N, Tidwell TJ, Yang T. Relative contributions of mitochondria and NADPH oxidase to deoxycorticosterone acetate-salt hypertension in mice. Kidney Int. 2011;80:51–60.
Yang Y, Zhang Y, Cuevas S, Villar VA, Escano C, D Asico L, et al. Paraoxonase 2 decreases renal reactive oxygen species production, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of NADPH oxidase. Free Radic Biol Med. 2012;53:437–46.
Ray R, Murdoch CE, Wang M, Santos CX, Zhang M, Alom-Ruiz S, et al. Endothelial Nox4 NADPH oxidase enhances vasodilatation and reduces blood pressure in vivo. Arterioscler Thromb Vasc Biol. 2011;31:1368–76.
Li H, Han X, Hu Z, Huang J, Chen J, Hixson JE, et al. Associations of NADPH oxidase-related genes with blood pressure changes and incident hypertension: The GenSalt Study. J Hum Hypertens. 2018;32:287–93.
Lai EY, Wellstein A, Welch WJ, Wilcox CS. Superoxide modulates myogenic contractions of mouse afferent arterioles. Hypertension. 2011;58:650–6.
Hsueh YM, Lin P, Chen HW, Shiue HS, Chung CJ, Tsai CT, et al. Genetic polymorphisms of oxidative and antioxidant enzymes and arsenic-related hypertension. J Toxicol Environ Health A. 2005;68:1471–84.
Conen D, Glynn RJ, Buring JE, Ridker PM, Zee RY. Association of renin–angiotensin and endothelial nitric oxide synthase gene polymorphisms with blood pressure progression and incident hypertension: Prospective Cohort Study. J Hypertens. 2008;26:1780–6.
Han X, Hu Z, Chen J, Huang J, Huang C, Liu F, et al. Associations between genetic variants of NADPH oxidase-related genes and blood pressure responses to dietary sodium intervention: The GenSalt Study. Am J Hypertens. 2017;30:427–34.
Godin N, Liu F, Lau GJ, Brezniceanu ML, Chénier I, Filep JG, et al. Catalase overexpression prevents hypertension and tubular apoptosis in angiotensinogen transgenic mice. Kidney Int. 2010;77:1086–97.
Bushueva OY, Ivanov VP, Ryzhaeva VN, Ponomarenko IV, Churnosov MI, Polonikov AV. Association of the −844G>A polymorphism in the catalase gene with the increased risk of essential hypertension in smokers. Ter Arkh. 2016;88:50–54.
Kouremenos N, Zacharopoulou IV, Triantafyllidi H, Zacharopoulos GV, Mornos C, Filippatos G, et al. Genes and genetic variations involved in the development of hypertension: focusing on a Greek patient cohort. Hell J Cardiol. 2014;55:9–16.
Zhou XF, Cui J, DeStefano AL, Chazaro I, Farrer LA, Manolis AJ, et al. Polymorphisms in the promoter region of catalase gene and essential hypertension. Dis Markers. 2005;21:3–7.
Jiang Z, Akey JM, Shi J, Xiong M, Wang Y, Shen Y, et al. A polymorphism in the promoter region of catalase is associated with blood pressure levels. Hum Genet. 2001;109:95–8.
Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, et al. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science. 2008;322:587–90.
Ishii I, Akahoshi N, Yamada H, Nakano S, Izumi T, Suematsu M. Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. J Biol Chem. 2010;285:26358–68.
Gupta V, Kapopara PR, Khan AA, Arige V, Subramanian L, Sonawane PJ, et al. Functional promoter polymorphisms direct the expression of cystathionine gamma-lyase gene in mouse models of essential hypertension. J Mol Cell Cardiol. 2017;102:61–73.
Mrozikiewicz PM, Bogacz A, Omielańczyk M, Wolski H, Bartkowiak-Wieczorek J, Grzeskowiak E, et al. The importance of rs1021737 and rs482843 polymorphisms of cystathionine gamma-lyase in the etiology of preeclampsia in the Caucasian population. Ginekol Pol. 2015;86:119–25.
Cuevas S, Zhang Y, Yang Y, Escano C, Asico L, Jones JE, et al. Role of renal DJ-1 in the pathogenesis of hypertension associated with increased reactive oxygen species production. Hypertension. 2012;59:446–52.
Cuevas S, Yang Y, Konkalmatt P, Asico LD, Feranil J, Jones J, et al. Role of renal DJ-1 in the pathogenesis of hypertension associated with increased reactive oxygenspecies production. Hypertension. 2012;59:446–52.
Yamane T, Murao S, Kozuka M, Shimizu M, Suzuki J, Kubo C, et al. Serum DJ-1 level is positively associated with improvements in some aspects of metabolic syndrome in Japanese women through lifestyle intervention. Nutr Res. 2014;34:851–5.
Albrecht FE, Drago J, Felder RA, Printz MP, Eisner GM, Robillard JE, et al. Role of the D1A dopamine receptor in the pathogenesis of genetic hypertension. J Clin Invest. 1996;97:2283–8.
Sato M, Soma M, Nakayama T, Kanmatsuse K. Dopamine D1 receptor gene polymorphism is associated with essential hypertension. Hypertension. 2000;36:183–6.
Orun O, Nacar C, Cabadak H, Tiber PM, Doğan Y, Güneysel Ö, et al. Investigation of the association between dopamine D1 receptor gene polymorphisms and essential hypertension in a group of Turkish subjects. Clin Exp Hypertens. 2011;33:418–21.
Zhang H, Sun ZQ, Liu SS, Yang LN. Association between GRK4 and DRD1 gene polymorphisms and hypertension: a meta-analysis. Clin Interv Aging. 2015;11:17–27.
Yang H, Zhong L, Bai S, Dong Y, Wang Y, Li Q, et al. Association of dopamine D1 and D3 receptor gene polymorphisms with essential hypertension in 3 ethnic groups in China. Med Sci Monit Basic Res. 2017;23:234–9.
Staessen JA, Kuznetsova T, Zhang H, Maillard M, Bochud M, Hasenkamp S, et al. Blood pressure and renal sodium handling in relation to genetic variation in the DRD1 promoter and GRK4. Hypertension. 2008;51:1643–50.
Rosmond R, Rankinen T, Chagnon M, Pérusse L, Chagnon YC, Bouchard C, et al. Polymorphism in exon 6 of the dopamine D(2) receptor gene (DRD2) is associated with elevated blood pressure and personality disorders in men. J Hum Hypertens. 2001;15:553–8.
Jiang X, Konkalmatt P, Yang Y, Gildea J, Jones JE, Cuevas S, et al. Single-nucleotide polymorphisms of the dopamine D2 receptor increase inflammation and fibrosis in human renal proximal tubule cells. Hypertension. 2014;63:e74–80.
Choi MR, Kouyoumdzian NM, Rukavina Mikusic NL, Kravetz MC, Rosón MI, Rodríguez Fermepin M, et al. Renal dopaminergic system: pathophysiological implications and clinical perspectives. World J Nephrol. 2015;4:196–212.
Fang YJ, Thomas GN, Xu ZL, Fang JQ, Critchley JA, Tomlinson B. An affected pedigree member analysis of linkage between the dopamine D2 receptor gene TaqI polymorphism and obesity and hypertension. Int J Cardiol. 2005;102:111–6.
Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, et al. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet. 2003;12:205–16.
Thompson J, Thomas N, Singleton A, Piggott M, Lloyd S, Perry EK, et al. D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics. 1997;7:479–84.
Rayner B, Ramesar R. The importance of G protein-coupled receptor kinase 4 (GRK4) in pathogenesis of salt sensitivity, salt sensitive hypertension and response to antihypertensive treatment. Int J Mol Sci. 2015;16:5741–9.
Johnson TL, Tulis DA, Keeler BE, Virag JA, Lust RM, Clemens S. The dopamine D3 receptor knockout mouse mimics aging-related changes in autonomic function and cardiac fibrosis. PLoS ONE. 2013;8:e74116.
Asico LD, Ladines C, Fuchs S, Accili D, Carey RM, Semeraro C, et al. Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension. J Clin Invest. 1998;102:493–8.
Wang X, Escano CS, Asico L, Jones JE, Barte A, Lau YS, et al. Upregulation of renal D5 dopamine receptor ameliorates the hypertension in D3 dopamine receptor-deficient mice. Hypertension. 2013;62:295–301.
Shimada S, Hirabayashi M, Ishige K, Kosuge Y, Kihara T, Ito Y. Activation of dopamine D4 receptors is protective against hypoxia/reoxygenation-induced cell death in HT22 cells. J Pharmacol Sci. 2010;114:217–24.
Korobochka R, Gritsenko I, Gonen R, Ebstein RP, Ohel G. Association between a functional dopamine D4 receptor promoter region polymorphism (−C521T) and pre-eclampsia: a family-based study. Mol Hum Reprod. 2006;12:85–88.
Sen S, Nesse R, Sheng L, Stoltenberg SF, Gleiberman L, Burmeister M, et al. Association between a dopamine-4 receptor polymorphism and blood pressure. Am J Hypertens. 2005;18:1206–10.
Norman SM, Sullivan KM, Liu F, DiPaula BA, Jose PA, Kitchen CA, et al. Blood pressure and heart rate changes during clozapine treatment. Psychiatr Q. 2017;88:545–52.
Asico L, Zhang X, Jiang J, Cabrera D, Escano CS, Sibley DR, et al. Lack of renal dopamine D5 receptors promotes hypertension. J Am Soc Nephrol. 2011;22:82–9.
Hollon TR, Bek MJ, Lachowicz JE, Ariano MA, Mezey E, Ramachandran R, et al. Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive. J Neurosci. 2002;22:10801–10.
Yang Z, Asico LD, Yu P, Wang Z, Jones JE, Escano CS, et al. D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure. Am J Physiol Regul Integr Comp Physiol. 2006;290:R96–R104.
Lu Q, Yang Y, Villar VA, Asico L, Jones JE, Yu P, et al. D5 dopamine receptor decreases NADPH oxidase, reactive oxygen species and blood pressure via heme oxygenase-1. Hypertens Res. 2013;36:684–90.
Kawakami T, Puri N, Sodhi K, Bellner L, Takahashi T, Morita K, et al. Reciprocal effects of oxidative stress on heme oxygenase expression and activity contributes to reno-vascular abnormalities in EC-SOD knockout mice. Int J Hypertens. 2012;2012:740203.
Naganuma T, Nakayama T, Sato N, Fu Z, Soma M, Aoi N, et al. A haplotype-based case–control study examining human extracellular superoxide dismutase gene and essential hypertension. Hypertens Res. 2008;31:1533–40.
Park SY, Lee HJ, Ji SM, Kim ME, Jigden B, Lim JE, et al. ANTXR2 is a potential causative gene in the genome-wide association study of the blood pressure locus 4q21. Hypertens Res. 2014;37:811–7.
Rhee MY, Yang SJ, Oh SW, Park Y, Kim CI, Park HK, et al. Novel genetic variations associated with salt sensitivity in the Korean population. Hypertens Res. 2011;34:606–11.
Ren Y, Jiao X, Zhang L. Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci. 2018;25:469–73.
Ardanaz N, Yang XP, Cifuentes ME, Haurani MJ, Jackson KW, Liao TD, et al. Lack of glutathione peroxidase 1 accelerates cardiac-specific hypertrophy and dysfunction in angiotensin II hypertension. Hypertension. 2010;55:116–23.
Hao Y, Wu BG, Shi J, Chen YL, Sun ZQ, Zheng LQ, et al. Association of tag SNPs of GPx-3 with essential hypertension in rural Han Chinese in Fuxin, Liaoning, China. Chin Med J (Engl). 2011;124:2113–6.
Polonikov AV, Vialykh EK, Churnosov MI, Illig T, Freidin MB, Vasil’eva OV, et al. The C718T polymorphism in the 3′-untranslated region of glutathione peroxidase-4 gene is a predictor of cerebral stroke in patients with essential hypertension. Hypertens Res. 2012;35:507–12.
Vaziri ND, Wang XQ, Oveisi F, Rad B. Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Hypertension. 2000;36:142–6.
Polimanti R, Piacentini S, Lazzarin N, Re MA, Manfellotto D, Fuciarelli M. Glutathione S-transferase variants as risk factor for essential hypertension in Italian patients. Mol Cell Biochem. 2011;357:227–33.
Han JH, Lee HJ, Choi HJ, Yun KE, Kang MH. Lymphocyte DNA damage and plasma antioxidant status in Korean subclinical hypertensive patients by glutathione S-transferase polymorphism. Nutr Res Pract. 2017;11:214–22.
Xi B, Shen Y, Reilly KH, Wang X, Mi J. Recapitulation of four hypertension susceptibility genes (CSK, CYP17A1, MTHFR, and FGF5) in East Asians. Metabolism. 2013;62:196–203.
Canto P, Canto-Cetina T, Juárez-Velázquez R, Rosas-Vargas H, Rangel-Villalobos H, Canizales-Quinteros S, et al. Methylenetetrahydrofolate reductase C677T and glutathione S-transferase P1 A313G are associated with a reduced risk of preeclampsia in Maya-Mestizo women. Hypertens Res. 2008;31:1015–9.
Cruz-Gonzalez I, Corral E, Sanchez-Ledesma M, Sanchez-Rodriguez A, Martin-Luengo C, Gonzalez-Sarmiento R. An association between resistant hypertension and the null GSTM1 genotype. J Hum Hypertens. 2009;23:556–8.
Liu J, Li M, Qi ML, Liu XL, Li YH, Fu LY, et al. Association of −63A/C polymorphism of glutathione S-transferase M3 gene with essential hypertension in Chinese population [in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007;24:582–5.
Ndisang JF, Zhao W, Wang R. Selective regulation of blood pressure by heme oxygenase-1 in hypertension. Hypertension. 2002;40:315–21.
Wenzel P, Rossmann H, Müller C, Kossmann S, Oelze M, Schulz A, et al. Heme oxygenase-1 suppresses a pro-inflammatory phenotype in monocytes and determines endothelial function and arterial hypertension in mice and humans. Eur Heart J. 2015;36:3437–46.
Daenen KE, Martens P, Bammens B. Association of HO-1 (GT)n promoter polymorphism and cardiovascular disease: a reanalysis of the literature. Can J Cardiol. 2016;32:160–8.
Stout JM, Gousset MU, Drummond HA, Gray W 3rd, Pruett BE, Stec DE. Sex-specific effects of heme oxygenase-2 deficiency on renovascular hypertension. J Am Soc Hypertens. 2013;7:328–35.
Tornavaca O, Pascual G, Barreiro ML, Grande MT, Carretero A, Riera M, et al. Kidney androgen-regulated protein transgenic mice show hypertension and renal alterations mediated by oxidative stress. Circulation. 2009;119:1908–17.
de Quixano BB, Villena JA, Aranda M, Brils G1, Cuevas A, Hespel T, et al. Kidney androgen-regulated protein (KAP) transgenic mice are protected against high-fat diet induced metabolic syndrome. Sci Rep. 2017;7:16102.
Grande MT, Pascual G, Riolobos AS, Clemente-Lorenzo M, Bardaji B, Barreiro L, et al. Increased oxidative stress, the renin-angiotensin system, and sympathetic overactivation induce hypertension in kidney androgen-regulated protein transgenic mice. Free Radic Biol Med. 2011;51:1831–41.
Cheng J, Tao F, Liu Y, Venners SA, Hsu YH, Jiang, et al. Associations of methylenetetrahydrofolate reductase C677T genotype with blood pressure levels in Chinese population with essential hypertension. Clin Exp Hypertens. 2018;40:207–12.
Dell’Omo G, Penno G, Pucci L, Lucchesi D, Del Prato S, Pedrinelli R. Q192R paraoxonase (PON)1 polymorphism, insulin sensitivity, and endothelial function in essential hypertensive men. Clin Med Insights Cardiol. 2014;8:57–62.
Turgut Cosan D, Colak E, Saydam F, Yazıcı HU, Degirmenci I, Birdane A, et al. Association of paraoxonase 1 (PON1) gene polymorphisms and concentration with essential hypertension. Clin Exp Hypertens. 2016;38:602–7.
Zhao Q, Zhang J, Wang H. PGC-1α overexpression suppresses blood pressure elevation in DOCA-salt hypertensive mice. Biosci Rep. 2015;21:e00217, 35 pii.
Oberkofler H, Hölzl B, Esterbauer H, Xie M, Iglseder B, Krempler F, et al. Peroxisome proliferator-activated receptor-gamma coactivator-1 gene locus: associations with hypertension in middle-aged men. Hypertension. 2003;41:368–72.
Cheurfa N, Reis AF, Dubois-Laforgue D, Bellanné-Chantelot C, Timsit J, Velho G. The Gly482Ser polymorphism in the peroxisome proliferator-activated receptor-gamma coactivator-1 gene is associated with hypertension in type 2 diabetic men. Diabetologia. 2004;47:1980–3.
Andersen G, Wegner L, Jensen DP, Glümer C, Tarnow L, Drivsholm T, et al. PGC-1alpha Gly482Ser polymorphism associates with hypertension among Danish whites. Hypertension. 2005;45:565–70.
Yang Y, Cuevas S, Yang S, Villar VA, Escano C, Asico L, et al. Sestrin2 decreases renal oxidative stress, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of reactive oxygen species production. Hypertension. 2014;64:825–32.
Jin K, Vaziri ND. Salt-sensitive hypertension in mitochondrial superoxide dismutase deficiency is associated with intra-renal oxidative stress and inflammation. Clin Exp Nephrol. 2014;18:445–52.
Kandinov B, Drory VE, Tordjman K, Korczyn AD. Blood pressure measurements in a transgenic SOD1-G93A mouse model of amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2012;13:509–13.
Carlström M, Lai EY, Ma Z, Steege A, Patzak A, Eriksson UJ, et al. Superoxide dismutase 1 limits renal microvascular remodeling and attenuates arteriole and blood pressure responses to angiotensin II via modulation of nitric oxide bioavailability. Hypertension. 2010;56:907–13.
Wakisaka Y, Chu Y, Miller JD, Rosenberg GA, Heistad DD. Critical role for copper/zinc-superoxide dismutase in preventing spontaneous intracerebral hemorrhage during acute and chronic hypertension in mice. Stroke. 2010;41:790–7.
Zhang XM, Ellis EF. Superoxide dismutase decreases mortality, blood pressure, and cerebral blood flow responses induced by acute hypertension in rats. Stroke. 1991;22:489–94.
Collister JP, Taylor-Smith H, Drebes D, Nahey D, Tian J, Zimmerman MC. Angiotensin II-induced hypertension is attenuated by overexpressing copper/zinc superoxide dismutase in the brain organum vasculosum of the lamina terminalis. Oxid Med Cell Longev. 2016;2016:3959087.
Lopes RA, Neves KB, Tostes RC, Montezano AC, Touyz RM. Downregulation of nuclear factor erythroid 2-related factor and associated antioxidant genes contributes to redox-sensitive vascular dysfunction in hypertension. Hypertension. 2015;66:1240–50.
Hatcher J, Gu H, Cheng ZJ. SOD1 overexpression preserves baroreflex control of heart rate with an increase of aortic depressor nerve function. Oxid Med Cell Longev. 2016;2016:3686829.
Dikalova AE, Bikineyeva AT, Budzyn K, Nazarewicz RR, McCann L, Lewis W, et al. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res. 2010;107:106–16.
Kang PT, Chen CL, Ohanyan V, Luther DJ, Meszaros JG, Chilian WM, et al. Overexpressing superoxide dismutase 2 induces a supernormal cardiac function by enhancing redox-dependent mitochondrial function and metabolic dilation. J Mol Cell Cardiol. 2015;88:14–28.
Hodgson JM, Croft KD, Woodman RJ, Puddey IB, Bondonno CP, Wu JH, et al. Effects of vitamin E, vitamin C and polyphenols on the rate of blood pressure variation: results of two randomised controlled trials. Br J Nutr. 2014;112:1551–61.
Mansego ML, Solar Gde M, Alonso MP, Martínez F, Sáez GT, Escudero JC, et al. Polymorphisms of antioxidant enzymes, blood pressure and risk of hypertension. J Hypertens. 2011;29:492–500.
Jonsson LM, Rees DD, Edlund T, Marklund SL. Nitric oxide and blood pressure in mice lacking extracellular-superoxide dismutase. Free Radic Res. 2002;36:755–8.
Lob HE, Vinh A, Li L, Blinder Y, Offermanns S, Harrison DG. Role of vascular extracellular superoxide dismutase in hypertension. Hypertension. 2011;58:232–9.
Dong X, Li D, Liu H, Zhao Y. SOD3 and eNOS genotypes are associated with SOD activity and NOx. Exp Ther Med. 2014;8:328–34.
Yoshioka J, Imahashi K, Gabel SA, Chutkow WA, Burds AA, Gannon J, et al. Targeted deletion of thioredoxin-interacting protein regulates cardiac dysfunction in response to pressure overload. Circ Res. 2007;101:1328–38.
Kiermayer C, Northrup E, Schrewe A, Walch A, de Angelis MH, Schoensiegel F, et al. Heart-specific knockout of the mitochondrial thioredoxin reductase (Txnrd2) induces metabolic and contractile dysfunction in the aging myocardium. J Am Heart Assoc. 2015;4:e002153. pii
Rubattu S, Bianchi F, Busceti CL, Cotugno M, Stanzione R, Marchitti S, et al. Differential modulation of AMPK/PPARα/UCP2 axis in relation to hypertension and aging in the brain, kidneys and heart of two closely related spontaneously hypertensive rat strains. Oncotarget. 2015;6:18800–18.
Liu L, Liu J, Tian XY, Wong WT, Lau CW, Xu A, et al. Uncoupling protein-2 mediates DPP-4 inhibitor-induced restoration of endothelial function in hypertension through reducing oxidative stress. Antioxid Redox Signal. 2014;21:1571–81.
Di Castro S, Scarpino S, Marchitti S, Bianchi F, Stanzione R, Cotugno M, et al. Differential modulation of uncoupling protein 2 in kidneys of stroke-prone spontaneously hypertensive rats under high-salt/low-potassium diet. Hypertension. 2013;61:534–41.
Ji Q, Ikegami H, Fujisawa T, Kawabata Y, Ono M, Nishino M, et al. A common polymorphism of uncoupling protein 2 gene is associated with hypertension. J Hypertens. 2004;22:97–102.
Scheepers LE, Wei FF, Stolarz-Skrzypek K, Malyutina S, Tikhonoff V, Thijs L, et al. Xanthine oxidase gene variants and their association with blood pressure and incident hypertension: a population study. J Hypertens. 2016;34:2147–54.
Khambata RS, Ghosh SM, Ahluwalia A. “Repurposing” of xanthine oxidoreductase as a nitrite reductase: a new paradigm for therapeutic targeting in hypertension. Antioxid Redox Signal. 2015;23:340–53.
Chaves FJ, Corella D, Blesa S, Mansego ML, Marín P, Portoles O, et al. Xanthine oxidoreductase polymorphisms: influence in blood pressure and oxidative stress levels. Pharm Genom. 2007;17:589–96.
Pechánová O, Zicha J, Kojsová S, Dobesová Z, Jendeková L, Kunes J. Effect of chronic N-acetylcysteine treatment on the development of spontaneous hypertension. Clin Sci (Lond). 2006;110:235–42.
Martina V, Masha A, Gigliardi VR, Brocato L, Manzato E, Berchio A, et al. Long-term N-acetylcysteine and l-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes. Diabetes Care. 2008;31:940–94.
Renke M, Tylicki L, Rutkowski P, Larczynski W, Neuwelt A, Aleksandrowicz E, et al. The effect of N-acetylcysteine on blood pressure and markers of cardiovascular risk in non-diabetic patients with chronic kidney disease: a placebo-controlled, randomized, cross-over study. Med Sci Monit. 2010;16:PI13–118.
Wang LP, Fan SJ, Li SM, Wang XJ, Gao JL, Yang XH. Oxidative stress promotes myocardial fibrosis by upregulating KCa3.1 channel expression in AGT-REN double transgenic hypertensive mice. Pflug Arch. 2017;469:1061–71.
Aldini G, Altomare A, Baron G, Vistoli G, Carini M, Borsani L, et al. N-acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic Res. 2018; https://doi.org/10.1080/10715762.2018.1468564:1–12.
Zhang Y, Cuevas S, Asico LD, Escano C, Yang Y, Pascua AM, et al. Deficient dopamine D2 receptor function causes renal inflammation independently of high blood pressure. PLoS ONE. 2012;7:e38745.
Potje SR, Troiano JA, Graton ME, Ximenes VF, Nakamune AC, Antoniali C. Hypotensive and vasorelaxant effect of diapocynin in normotensive rats. Free Radic Biol Med. 2017;106:148–57.
Bhatia K, Elmarakby AA, El-Remessy AB, Sullivan JC. Oxidative stress contributes to sex differences in angiotensin II-mediated hypertension in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2012;302:R274–282.
Li Z, Wang Y, Man RY, Vanhoutte PM. Upregulation of heme oxygenase-1 potentiates EDH-type relaxations in the mesenteric artery of the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol. 2013;305:H1471–1483.
Armando I, Wang X, Villar VA, Jones JE, Asico LD, Escano C, et al. Reactive oxygen species-dependent hypertension in dopamine D2 receptor-deficient mice. Hypertension. 2007;49:672–8.
Wang HP, Yang J, Qin LQ, Yang XJ. Effect of garlic on blood pressure: a meta-analysis. J Clin Hypertens (Greenwich). 2015;17:223–31.
Ried K. Garlic lowers blood pressure in hypertensive individuals, regulates serum cholesterol, and stimulates immunity: an updated meta-analysis and review. J Nutr. 2016;146:389S–396S.
Dhawan V, Jain S. Garlic supplementation prevents oxidative DNA damage in essential hypertension. Mol Cell Biochem. 2005;275:85–94.
Castro C, Lorenzo AG, González A, Cruzado M. Garlic components inhibit angiotensin II-induced cell-cycle progression and migration: involvement of cell-cycle inhibitorp27(Kip1) and mitogen-activated protein kinase. Mol Nutr Food Res. 2010;54:781–7.
Siani A, Pagano E, Iacone R, Iacoviello L, Scopacasa F, Strazzullo P. Blood pressure and metabolic changes during dietary l-arginine supplementation in humans. Am J Hypertens. 2000;13:547–51.
Rajapakse NW, Karim F, Evans RG, Kaye DM, Head GA. Augmented endothelial-specific l-arginine transport blunts the contribution of the sympathetic nervous system to obesity induced hypertension in mice. PLoS ONE. 2015;10:e0131424.
Vanhoutte PM, Zhao Y, Xu A, Leung SW. Thirty years of saying NO: sources, fate, actions, and misfortunes of the endothelium-derived vasodilator mediator. Circ Res. 2016;119:375–96.
Zoja C, Corna D, Nava V, Locatelli M, Abbate M, Gaspari F, et al. Analogs of bardoxolone methyl worsen diabetic nephropathy in rats with additional adverse effects. Am J Physiol Ren Physiol. 2013;304:F808–819.
Zeeuw D, Akizawa T, Audhya P, Bakris GL, Chin M, Christ-Schmidt H, et al., BEACON Trial Investigators. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med. 2013;369:2492–503. .
Blanca AJ, Ruiz-Armenta MV, Zambrano S, Miguel-Carrasco JL, Arias JL, Arévalo M, et al. Inflammatory and fibrotic processes are involved in the cardiotoxic effect of sunitinib: protective role of l-carnitine. Toxicol Lett. 2016;241:9–18.
Graham D, Huynh NN, Hamilton CA, Beattie E, Smith RA, Cochemé HM, et al. Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy. Hypertension. 2009;54:322–8.
Ruggenenti P, Cattaneo D, Loriga G, Ledda F, Motterlini N, Gherardi G, et al. Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-l-carnitine therapy. Hypertension. 2009;54:567–74.
Takahashi R, Asai T, Murakami H, Murakami R, Tsuzuki M, Numaguchi Y, et al. Pressure overload-induced cardiomyopathy in heterozygous carrier mice of carnitine transporter gene mutation. Hypertension. 2007;50:497–450.
Mingorance C, Duluc L, Chalopin M, Simard G, Ducluzeau PH, Herrera MD, et al. Propionyl-l-carnitine corrects metabolic and cardiovascular alterations in diet-induced obese mice and improves liver respiratory chain activity. PLoS ONE. 2012;7:e34268.
San Cheang W, Yuen Ngai C, Yen Tam Y, Yu Tian X, Tak Wong W, Zhang Y, et al. Black tea protects against hypertension-associated endothelial dysfunction through alleviation of endoplasmic reticulum stress. Sci Rep. 2015;5:10340.
Serban C, Sahebkar A, Ursoniu S, Andrica F, Banach M. Effect of sour tea (Hibiscus sabdariffa L.) on arterial hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2015;33:1119–27.
Sugita M, Kapoor MP, Nishimura A, Okubo T. Influence of green tea catechins on oxidative stress metabolites at rest and during exercise in healthy humans. Nutrition. 2016;32:321–31.
Burke BE, Neuenschwander R, Olson RD. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J. 2001;94:1112–7.
Singh RB, Niaz MA, Rastogi SS, Shukla PK, Thakur AS. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens. 1999;13:203–8.
Luna-Sánchez M, Hidalgo-Gutiérrez A, Hildebrandt TM, Chaves-Serrano J, Barriocanal-Casado E, Santos-Fandila Á, et al. CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome. EMBO Mol Med. 2017;9:78–95.
Ankola DD, Viswanad B, Bhardwaj V, Ramarao P, Kumar MN. Development of potent oral nanoparticulate formulation of coenzyme Q10 for treatment of hypertension: can the simple nutritional supplements be used as first line therapeutic agents for prophylaxis/therapy? Eur J Pharm Biopharm. 2007;67:361–9.
Nakmareong S, Kukongviriyapan U, Pakdeechote P, Kukongviriyapan V, Kongyingyoes B, Donpunha W, et al. Tetrahydrocurcumin alleviates hypertension, aortic stiffening and oxidative stress in rats with nitric oxide deficiency. Hypertens Res. 2012;35:418–25.
Kukongviriyapan U, Pannangpetch P, Kukongviriyapan V, Donpunha W, Sompamit K, Surawattanawan P. Curcumin protects against cadmium-induced vascular dysfunction, hypertension and tissue cadmium accumulation in mice. Nutrients. 2014;21:1194–208.
Cicero AFG, Fogacci F, Colletti A. Food and plant bioactives for reducing cardiometabolic disease risk: an evidence based approach. Food Funct. 2017;8:2076–88.
Wang S, Ye Q, Tu J, Zhang M, Ji B. Curcumin protects against hypertension aggravated retinal ischemia/reperfusion in a rat stroke model. Clin Exp Hypertens. 2017;39:711–7.
El-Bassossy HM, Hassan N, Zakaria MN. Heme oxygenase-1 alleviates vascular complications associated with metabolic syndrome: effect on endothelial dependent relaxation and NO production. Chem Biol Interact. 2014;223:109–15.
Sirivarasai J, Kaojarern S, Chanprasertyothin S, Panpunuan P, Petchpoung K, Tatsaneeyapant A, et al. Environmental lead exposure, catalase gene, and markers of antioxidant and oxidative stress relation to hypertension: an analysis based on the EGAT study. Biomed Res Int. 2015;2015:856319.
Lu Q, Yang Y, Villar VA, Asico L, Jones JE, Yu P, et al. D5 dopamine receptor decreases NADPH oxidase, reactive oxygen species and blood pressure via heme oxygenase-1. Hypertens Res. 2013;36:684–90.
Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi M. Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res. 2015;29:323–31.
Wunpathe C, Potue P, Maneesai P, Bunbupha S, Prachaney P, Kukongviriyapan U, et al. Hesperidin suppresses renin–angiotensin system mediated NOX2 over-expression and sympathoexcitation in 2K-1C hypertensive rats. Am J Chin Med. 2018;13:1–17.
Salden BN, Troost FJ, de Groot E, Stevens YR, Garcés-Rimón M, Possemiers S, et al. Randomized clinical trial on the efficacy of hesperidin 2S on validated cardiovascular biomarkers in healthy overweight individuals. Am J Clin Nutr. 2016;104:1523–1153.
Koçak G, Aktan F, Canbolat O, Ozoğul C, Elbeğ S, Yildizoglu-Ari N, et al. Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reactivity and morphology of vessels already damaged by streptozotocin-diabetes. Diabetes Nutr Metab. 2000;13:308–18.
Mohammadi V, Dehghani S, Askari G. Does alpha-lipoic acid supplement regulate blood pressure? A systematic review of randomized, double-blind placebo-controlled clinical trials. Int J Prev Med. 2017;8:33.
de Queiroz TM, Xia H, Filipeanu CM, Braga VA, Lazartigues E. α-Lipoic acid reduces neurogenic hypertension by blunting oxidative stress-mediated increase in ADAM17. Am J Physiol Heart Circ Physiol. 2015;309:H926–934.
Grossman E, Laudon M, Zisapel N. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials. Vasc Health Risk Manag. 2011;7:577–84.
Rahman MM, Kwon HS, Kim MJ, Go HK, Oak MH, Kim DH. Melatonin supplementation plus exercise behavior ameliorate insulin resistance, hypertension and fatigue in a rat model of type 2 diabetes mellitus. Biomed Pharmacother. 2017;92:606–14.
Klimentova J, Cebova M, Barta A, Matuskova Z, Vrankova S, Rehakova R, et al. Effect of melatonin on blood pressure and nitric oxide generation in rats with metabolic syndrome. Physiol Res. 2016;65:S373–380.
Qiao YF, Guo WJ, Li L, Shao S, Qiao X, Shao JJ, et al. Melatonin attenuates hypertension-induced renal injury partially through inhibiting oxidative stress in rats. Mol Med Rep. 2016;13:21–26.
Plotnikov MB, Aliev OI, Sidekhmenova AV, Shamanaev AY, Anishchenko AM, Nosarev AV, et al. Modes of hypotensive action of dihydroquercetin in arterial hypertension. Bull Exp Biol Med. 2017;162:353–6.
Gormaz JG, Quintremil S, Rodrigo R. Cardiovascular disease: a target for the pharmacological effects of quercetin. Curr Top Med Chem. 2015;15:1735–42.
Egert S, Bosy-Westphal A, Seiberl J, Kurbitz C, Settler U, Plachta-Danielzik S, et al. Quercetin reduces systolic blood pressure and plasma oxidised lowdensity lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr. 2009;102:1065–74.
Ko WC, Shih CM, Chen MC, Lai YH, Chen JH, Chen CM, et al. Suppressive effects of 3-O-methylquercetin on ovalbumin-induced airway hyperresponsiveness. Planta Med. 2004;70:1123–7.
Dolinsky VW, Chakrabarti S, Pereira TJ, Oka T, Levasseur J, Beker D, et al. Resveratrol prevents hypertension and cardiac hypertrophy in hypertensive rats and mice. Biochim Biophys Acta. 2013;1832:1723–33.
Tain YL, Lin YJ, Sheen JM, Lin IC, Yu HR, Huang LT, et al. Resveratrol prevents the combined maternal plus postweaning high-fat-diets-induced hypertension in male offspring. J Nutr Biochem. 2017;48:120–7.
Diao Z, Asico LD, Villar VAM, Zheng X, Cuevas S, Armando I, et al. Increased renal oxidative stress in salt-sensitive human GRK4γ486V transgenic mice. Free Radic Biol Med. 2017;106:80–90.
Geetha R, Yogalakshmi B, Sreeja S, Bhavani K, Anuradha CV. Troxerutin suppresses lipid abnormalities in the heart of high-fat-high-fructose diet-fed mice. Mol Cell Biochem. 2014;387:123–34.
Yu Y, Zheng G. Troxerutin protects against diabetic cardiomyopathy through NF‑κB/AKT/IRS1 in a rat model of type 2 diabetes. Mol Med Rep. 2017;15:3473–8.
Jaja SI, Ogungbemi SI, Kehinde MO. Electrocardiographic and blood pressure changes in apparently healthy male subjects following oral, chronic, low-dose vitamin C supplementation and/or change in posture. Nig Q J Hosp Med. 2008;18:96–100.
Chen X, Touyz RM, Park JB, Schiffrin EL. Antioxidant effects of vitamins C and E are associated with altered activation of vascular NADPH oxidase and superoxide dismutase in stroke-prone SHR. Hypertension. 2001;38:606–11.
Bruno RM, Daghini E, Ghiadoni L, Sudano I, Rugani I, Varanini M, et al. Effect of acute administration of vitamin C on muscle sympathetic activity, cardiac sympathovagal balance, and baroreflex sensitivity in hypertensive patients. Am J Clin Nutr. 2012;96:302–8.
Rodrigo R, Prat H, Passalacqua W, Araya J, Bächler JP. Decrease in oxidative stress through supplementation of vitamins C and E is associated with a reduction in blood pressure in patients with essential hypertension. Clin Sci (Lond). 2008;114:625–34.
Donpunha W, Kukongviriyapan U, Sompamit K, Pakdeechote P, Kukongviriyapan V, Pannangpetch P. Protective effect of ascorbic acid on cadmium-induced hypertension and vascular dysfunction in mice. Biometals. 2011;24:105–15.
Ahmad KA, Yuan Yuan D, Nawaz W, Ze H, Zhuo CX, Talal B, et al. Antioxidant therapy for management of oxidative stress induced hypertension. Free Radic Res. 2017;51:428–38.
Juraschek SP, Guallar E, Appel LJ, Miller ER 3rd. Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012;95:1079–88.
Witham MD, Nadir MA, Struthers AD. Effect of vitamin D on blood pressure: a systematic review and meta-analysis. J Hypertens. 2009;27:1948–54.
Mirhosseini NZ, Knaus SJ, Bohaychuk K, Singh J, Vatanparast HA, Weber LP. Both high and low plasma levels of 25-hydroxy vitamin D increase blood pressure in a normal rat model. Br J Nutr. 2016;116:1889–1900.
Pilz S, Gaksch M, Kienreich K, Grübler M, Verheyen N, Fahrleitner-Pammer A, et al. Effects of vitamin D on blood pressure and cardiovascular risk factors: a randomized controlled trial. Hypertension. 2015;65:1195–201.
Ni W, Watts SW, Ng M, Chen S, Glenn DJ, Gardner DG. Elimination of vitamin D receptor in vascular endothelial cells alters vascular function. Hypertension. 2014;64:1290–8.
Pelham CJ, Drews EM, Agrawal DK. Vitamin D controls resistance artery function through regulation of perivascular adipose tissue hypoxia and inflammation. J Mol Cell Cardiol. 2016;98:1–10.
Franczyk A, Stolarz-Skrzypek K, Wesołowska A, Czarnecka D. Vitamin D and vitamin D receptor activators in treatment of hypertension and cardiovascular disease. Cardiovasc Hematol Disord Drug Targets. 2014;14:34–44.
Faulkner JL, Amaral LM, Cornelius DC, Cunningham MW, Ibrahim T, Heep A, et al. Vitamin D supplementation reduces some AT1-AA-induced downstream targets implicated in preeclampsia including hypertension. Am J Physiol Regul Integr Comp Physiol. 2017;312:R125–131.
Beveridge LA, Struthers AD, Khan F, Jorde R, Scragg R, Macdonald HM, et al., D-PRESSURE Collaboration. Effect of vitamin D supplementation on blood pressure: a systematic review and meta-analysis incorporating individual patient data. JAMA Intern Med. 2015;175:745–54. .
Trehan N, Afonso L, Levine DL, Levy PD. Vitamin D deficiency, supplementation, and cardiovascular health. Crit Pathw Cardiol. 2017;16:109–18.
Al Mheid I, Quyyumi AA. Vitamin D and cardiovascular disease: controversy unresolved. J Am Coll Cardiol. 2017;70:89–100.
Legarth C, Grimm D, Wehland M, Bauer J, Krüger M. The impact of vitamin D in the treatment of essential hypertension. Int J Mol Sci. 2018;19:E455.
Mirhosseini NZ, Knaus SJ, Bohaychuk K, Singh J, Vatanparast HA, Weber LP. Both high and low plasma levels of 25-hydroxy vitamin D increase blood pressure in a normal rat model. Br J Nutr. 2016;116:1889–1900.
Oh J, Riek AE, Zhang RM, Williams SAS, Darwech I, Bernal-Mizrachi C. Deletion of JNK2 prevents vitamin-D-deficiency-induced hypertension and atherosclerosis in mice. J Steroid Biochem Mol Biol. 2018;177:179–86.
Boshtam M, Rafiei M, Sadeghi K, Sarraf-Zadegan N. Vitamin E can reduce blood pressure in mild hypertensives. Int J Vitam Nutr Res. 2002;72:309–14.
Barbagallo M, Dominguez LJ, Tagliamonte MR, Resnick LM, Paolisso G. Effects of vitamin E and glutathione on glucose metabolism: role of magnesium. Hypertension. 1999;34:1002–6.
Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S. Vitamin E as a potential interventional treatment for metabolic syndrome: evidence from animal and human studies. Front Pharmacol. 2017;8:444.
Azzi A. Many tocopherols, one vitamin E. Mol Asp Med. 2018;61:92–103.
Galley HF, Thornton J, Howdle PD, Walker BE, Webster NR. Combination oral antioxidant supplementation reduces blood pressure. Clin Sci (Lond). 1997;92:361–5.
Wigley RD, Vlieg M. Alpha tocopherol and blood pressure in PN/n mice. Aust J Exp Biol Med Sci. 1978;56:631–7.
Saremi A, Arora R. Vitamin E and cardiovascular disease. Am J Ther. 2010;17:e56–65.
Konety BR, Leman E, Vietmeier B, Arlotti J, Dhir R, Getzenberg RH. In vitro and in vivo effects of vitamin D (calcitriol) administration on the normal neonatal and prepubertal prostate. J Urol. 2000;164:1812–8.
Montezano AC, Touyz RM. Reactive oxygen species, vascular Noxs, and hypertension: focus on translational and clinical research. Antioxid Redox Signal. 2014;20:164–82.
Ando K, Fujita M. Reactive oxygen species and the central nervous system in salt-sensitive hypertension: possible relationship with obesity-induced hypertension. Clin Exp Pharmacol Physiol. 2012;39:111–6.
Giordano FJ. Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest. 2005;115:500–8.
Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol. 2004;4:181–9.
Montezano AC, Tsiropoulou S, Dulak-Lis M, Harvey A, Camargo Lde L, Touyz RM. Redox signaling, Nox5 and vascular remodeling in hypertension. Curr Opin Nephrol Hypertens. 2015;24:425–33.
Stasia MJ. CYBA encodingp22(phox), the cytochrome b558 alpha polypeptide: gene structure, expression, role and physiopathology. Gene. 2016;586:27–35.
Wang H, Albadawi H, Siddiquee Z, Stone JM, Panchenko MP, Watkins MT, et al. Altered vascular activation due to deficiency of the NADPH oxidase component p22phox. Cardiovasc Pathol. 2014;23:35–42.
Zalba G, San José G, Beaumont FJ, Fortuño MA, Fortuño A, Díez J, et al. Polymorphisms and promoter overactivity of thep22(phox) gene in vascular smooth muscle cells from spontaneously hypertensive rats. Circ Res. 2001;88:217–22.
Schreiber R, Ferreira-Sae MC, Tucunduva AC, Mill JG, Costa FO, Krieger JE, et al. CYBA C242T polymorphism is associated with obesity and diabetes mellitus in Brazilian hypertensive patients. Diabet Med. 2012;29:e55–61.
Rafiq A, Aslam K, Malik R, Afroze D. C242T polymorphism of the NADPH oxidase p22PHOX gene and its association with endothelial dysfunction in asymptomatic individuals with essential systemic hypertension. Mol Med Rep. 2014;9:1857–62.
Kumar R, Kohli S, Ali Z, Duhan K, Ram R, Gupta M, et al. CYBA (p22phox) variants associate with blood pressure and oxidative stress markers in hypertension: a replication study in populations of diverse altitudes. Hypertens Res. 2015;38:498–506.
Yu P, Han W, Villar VA, Yang Y, Lu Q, Lee H, et al. Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells. Redox Biol. 2014;2:570–9.
Wang Y, Chen F, Le B, Stepp DW, Fulton DJ. Impact of Nox5 polymorphisms on basal and stimulus-dependent ROS generation. PLoS ONE. 2014;9:e100102.
Holterman CE, Thibodeau JF, Towaij C, Gutsol A, Montezano AC, Parks RJ, et al. Nephropathy and elevated BP in mice with podocyte-specific NADPH oxidase 5 expression. J Am Soc Nephrol. 2014;25:784–97.
Heimlich JB, Speed JS, O’Connor PM, Pollock JS, Townes TM, Meiler SE, et al. Endothelin-1 contributes to the progression of renal injury in sickle cell disease via reactive oxygen species. Br J Pharmacol. 2016;173:386–95.
Gupta RM, Hadaya J, Trehan A, Zekavat SM, Roselli C, Klarin D, et al. A genetic variant associated with five vascular diseases is a distal regulator of endothelin-1 gene expression. Cell. 2017;170:522–33.
Brennan ML, Anderson MM, Shih DM, Qu XD, Wang X, Mehta AC, et al. Increased atherosclerosis in myeloperoxidase-deficient mice. J Clin Invest. 2001;107:419–30.
Nishino T, Okamoto K, Eger BT, Pai EF, Nishino T. Mammalian xanthine oxidoreductase—mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 2008;275:3278–89.
Wright RM, Vaitaitis GM, Wilson CM, Repine TB, Terada LS, Repine JE. cDNA cloning, characterization, and tissue-specific expression of human xanthine dehydrogenase/xanthine oxidase. Proc Natl Acad Sci USA. 1993;90:10690–4.
Van Hee VC, Adar SD, Szpiro AA, Barr RG, Diez Roux A, Bluemke DA, et al. Common genetic variation, residential proximity to traffic exposure, and left ventricular mass: the multi-ethnic study of atherosclerosis. Environ Health Perspect. 2010;118:962–9.
Quintana LF, Guzmán B, Collado S, Clària J, Poch E. A coding polymorphism in the 12-lipoxygenase gene is associated to essential hypertension and urinary 12(S)-HETE. Kidney Int. 2006;69:526–30.
Kriska T, Cepura C, Magier D, Siangjong L, Gauthier KM, Campbell WB. Mice lacking macrophage 12/15-lipoxygenase are resistant to experimental hypertension. Am J Physiol Heart Circ Physiol. 2012;302:H2428–2438.
Huan T, Esko T, Peters MJ, Pilling LC, Schramm K, Schurmann C, et al. A meta-analysis of gene expression signatures of blood pressure and hypertension. PLoS Genet. 2015;11:e1005035.
Stæhr M, Hansen PB, Madsen K, Vanhoutte PM, Nüsing RM, Jensen BL. Deletion of cyclooxygenase-2 in the mouse increases arterial blood pressure with no impairment in renal NO production in response to chronic high salt intake. Am J Physiol Regul Integr Comp Physiol. 2013;304:R899–8907.
Eirin A, Lerman A, Lerman LO. Mitochondria: a pathogenic paradigm in hypertensive renal disease. Hypertension. 2015;65:264–70.
Lee H, Abe Y, Lee I, Shrivastav S, Crusan AP, Hüttemann M, et al. Increased mitochondrial activity in renal proximal tubule cells from young spontaneously hypertensive rats. Kidney Int. 2014;85:561–9.
Dikalova AE, Bikineyeva AT, Budzyn K, Nazarewicz RR, McCann L, Lewis W, et al. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res. 2010;107:106–16.
Bajpai P, Srinivasan S, Ghosh J, Nagy LD, Wei S, Guengerich FP, et al. Targeting of splice variants of human cytochrome P450 2C8 (CYP2C8) to mitochondria and their role in arachidonic acid metabolism and respiratory dysfunction. J Biol Chem. 2014;289:29614–30.
Yan HC, Liu JH, Li J, He BX, Yang L, Qiu J, et al. Association between the CYP4A11 T8590C variant and essential hypertension: new data from Han Chinese and a meta-analysis. PLoS One. 2013;8:e80072.
Gregoski MJ, Buxbaum SG, Kapuku G, Dong Y, Zhu H, Davis M, et al. Interactive influences of ethnicity, endothelin-1 gene, and everyday discrimination upon nocturnal ambulatory blood pressure. Ann Behav Med. 2013;45:377–86.
Hermann M, Hellermann JP, Quitzau K. CYP4A11 polymorphism correlates with coronary endothelial dysfunction in patients with coronary artery disease—the ENCORE Trials. Atherosclerosis. 2009;207:476–9.
Polonikov AV, Ivanov VP, Solodilova MA. CYP2E1 gene promoter polymorphism −1293G>C increases the risk of essential hypertension in men with alcohol abuse. Bull Exp Biol Med. 2013;155:734–7.
Capdevila J, Wang W. Role of cytochrome P450 epoxygenase in regulating renal membrane transport and hypertension. Curr Opin Nephrol Hypertens. 2013;22:163–9.
Huber M, Lezius S, Reibis R, Treszl A, Kujawinska D, Jakob S, et al. A single nucleotide polymorphism near the CYP17A1 gene is associated with left ventricular mass in hypertensive patients under pharmacotherapy. Int J Mol Sci. 2015;16:17456–68.
Yao B, Harris RC, Zhang MZ. Intrarenal dopamine attenuates deoxycorticosterone acetate/high salt-induced blood pressure elevation in part through activation of a medullary cyclooxygenase 2 pathway. Hypertension. 2009;54:1077–83.
Zhang MZ, Harris RC. Antihypertensive mechanisms of intra-renal dopamine. Curr Opin Nephrol Hypertens. 2015;24:117–22.
Zhang MZ, Yao B, Wang S, Fan X, Wu G, Yang H, et al. Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice. J Clin Invest. 2011;121:2845–54.
Zhang MZ, Wang Y, Yao B, Gewin L, Wei S, Capdevila JH, et al. Role of epoxyeicosatrienoic acids (EETs) in mediation of dopamine’s effects in the kidney. Am J Physiol Ren Physiol. 2013;305:F1680–1686.
Andres-Mateos E, Perier C, Zhang L, Blanchard-Fillion B, Greco TM, Thomas B, et al. DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase. Proc Natl Acad Sci USA. 2007;104:14807–12.
Rubattu S, Pagliaro B, Pierelli G, Santolamazza C, Castro SD, Mennuni S, et al. Pathogenesis of target organ damage in hypertension: role of mitochondrial oxidative stress. Int J Mol Sci. 2014;16:823–39.
de Souza BM, Michels M, Sortica DA, Bouças AP, Rheinheimer J, Buffon MP, et al. Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney. PLoS ONE. 2015;10:e0132938.
Rybka J, Kupczyk D, Kędziora-Kornatowska K, Motyl J, Czuczejko J, Szewczyk-Golec K, et al. Glutathione-related antioxidant defense system in elderly patients treated for hypertension. Cardiovasc Toxicol. 2011;11:1–9.
Boyer TD. The glutathione S-transferases: an update. Hepatology. 1989;9:486–96.
Palmer CN, Turck N, Robin X, Walter N, Fouda C, Hainard A, et al. lood glutathione S-transferase-π as a time indicator of stroke onset PLoS ONE 2012;7:e43830.
Oniki K, Hori M, Takata K, Yokoyama T, Mihara S, Marubayashi T, et al. Association between glutathione S-transferase A1, M1 and T1 polymorphisms and hypertension. Pharm Genom. 2008;18:275–277.
Zusterzeel PL, Visser W, Peters WH, Merkus HW, Nelen WL, Steegers EA. Polymorphism in the glutathione S transferase P1 gene and risk for preeclampsia. Obstet Gynecol. 2000;96:50–54.
Ge B, Song Y, Zhang Y, Liu X, Wen Y, Guo X, et al. Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null polymorphisms and the risk of hypertension: a meta-analysis. PLoS ONE. 2015;10:e0118897.
Wang Y, Branicky R, Noë A, Hekimi S. Superoxide dismutases: dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol. 2018;217:1915–28.
Alili R, Nivet-Antoine V, Saldmann A, Golmard JL, Cottart CH, Laguillier C, et al. Human catalase gene promoter haplotype and cardiometabolic improvement after bariatric surgery. Gene. 2018;656:17–21.
Kasperczyk S, Kasperczyk J, Ostałowska A, Zalejska-Fiolka J, Wielkoszyński T, Swietochowska E, et al. The role of the antioxidant enzymes in erythrocytes in the development of arterial hypertension among humans exposed to lead. Biol Trace Elem Res. 2009;130:95–106.
Lacy F, O’Connor DT, Schmid-Schönbein GW. Plasma hydrogen peroxide production in hypertensives and normotensive subjects at genetic risk of hypertension. J Hypertens. 1998;16:291–303.
Lacy F, Kailasam MT, O’Connor DT, Schmid-Schönbein GW, Parmer RJ. Plasma hydrogen peroxide production in human essential hypertension: role of heredity, gender, and ethnicity. Hypertension. 2000;36:878–84.
Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev. 2003;24:78–90.
Chen SD, Yang DI, Lin TK, Shaw FZ, Liou CW, Chuang YC. Roles of oxidative stress, apoptosis, PGC-1α and mitochondrial biogenesis in cerebral ischemia. Int J Mol Sci. 2011;12:7199–215.
Togliatto G, Lombardo G, Brizzi MF. The future challenge of reactive oxygen species (ROS) in hypertension: from bench to bed side. Int J Mol Sci. 2017;18:E1988. pii
Mihalj M, Tadzic R, Vcev A, Rucevic S, Drenjancevic I. Blood pressure reduction is associated with the changes in oxidative stress and endothelial activation in hypertension, regardless of antihypertensive therapy. Kidney Blood Press Res. 2016;41:721–35.
Chin MP, Bakris GL, Block GA, Chertow GM, Goldsberry A, Inker LA, et al. Bardoxolone methyl improves kidney function in patients with chronic kidney disease stage 4 and type 2 diabetes: post-hoc analyses from bardoxolone methyl evaluation in patients with chronic kidney disease and type 2 diabetes study. Am J Nephrol. 2018;47:40–7.
Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37–46.
Schwingshackl L, Boeing H, Stelmach-Mardas M, Gottschald M, Dietrich S, Arregui M, et al. Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a systematic review and meta-analysis of primary prevention trials. Adv Nutr. 2017;8:27–39.
Xiao L, Dong JH, Teng X, Jin S, Xue HM, Liu SY, et al. Hydrogen sulfide improves endothelial dysfunction in hypertension by activating peroxisome proliferator-activated receptor delta/endothelial nitric oxide synthase signaling. J Hypertens. 2018;36:651–65.
Van Goor H, van den Born JC, Hillebrands JL, Joles JA. Hydrogen sulfide in hypertension. Curr Opin Nephrol Hypertens. 2016;25:107–13.
de Zeeuw D, Akizawa T, Audhya P, Bakris GL, Chin M, Christ-Schmidt H, et al. BEACON Trial Investigators. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med. 2013;369:2492–503.
Rossing P. Diabetic nephropathy: could problems with bardoxolone methyl have been predicted? Nat Rev Nephrol. 2013;9:128–30.
Himmelfarb J, Tuttle KR. Bardoxolone methyl in type 2 diabetes and advanced chronic kidney disease. N Engl J Med. 2014;370:1768–9.
Duffy SJ, Gokce N, Holbrook M, Huang A, Frei B, Keaney JF Jr, et al. Treatment of hypertension with ascorbic acid. Lancet. 1999;354:2048–9.
Mullan BA, Young IS, Fee H, McCance DR. Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes. Hypertension. 2002;40:804–9.
Czernichow S, Bertrais S, Blacher J, Galan P, Briançon S, Favier A, et al. Effect of supplementation with antioxidants upon long-term risk of hypertension in the SU.VI.MAX study: association with plasma antioxidant levels. J Hypertens. 2005;23:2013–8.
Kim MK, Sasaki S, Sasazuki S, Okubo S, Hayashi M, Tsugane S. Lack of long-term effect of vitamin C supplementation on blood pressure. Hypertension. 2002;40:797–803.
Borghi C, Cicero AF. Nutraceuticals with a clinically detectable blood pressure-lowering effect: a review of available randomized clinical trials and their meta-analyses. Br J Clin Pharmacol. 2017;83:163–71.
Kamper M, Tsimpoukidi O, Chatzigeorgiou A, Lymberi M, Kamper EF. The antioxidant effect of angiotensin II receptor blocker, losartan, in streptozotocin-induced diabetic rats. Transl Res. 2010;156:26–36.
Molteni A, Ward WF, Ts’ao CH, Taylor J, Small W Jr, Brizio-Molteni L, et al. Cytostatic properties of some angiotensin I converting enzyme inhibitors and of angiotensin II type I receptor antagonists. Curr Pharm. 2003;9:751–61.
Chopra M, McMurray J, Stewart J, Dargie HJ, Smith WE. Free radical scavenging: a potentially beneficial action of thiol-containing angiotensin converting enzyme inhibitors. Biochem Soc Trans. 1990;18:1184–5.
Dalbeth N, Edwards J, Fairchild S, Callan M, Hall FC. The non-thiol angiotensin-converting enzyme inhibitor quinapril suppresses inflammatory arthritis. Rheumatology (Oxf). 2005;44:24–31.
Bucci M, Vellecco V, Cantalupo A, Brancaleone V, Zhou Z, Evangelista S, et al. Hydrogen sulfide accounts for the peripheral vascular effects of zofenopril independently of ACE inhibition. Cardiovasc Res. 2014;102:138–47.
Moser M, Frishman W. Results of therapy with carvedilol, a beta-blocker vasodilator with antioxidant properties, in hypertensive patients. Am J Hypertens. 1998;1 Part 2: 15S–22S.
Gomes A, Costa D, Lima JL, Fernandes E. Antioxidant activity of beta-blockers: an effect mediated by scavenging reactive oxygen and nitrogen species? Bioorg Med Chem. 2006;14:4568–77.
Tomino Y. Renoprotective effects of the L-/T-type calcium channel blocker benidipine in patients with hypertension. Curr Hypertens Rev. 2013;9:108–14.
do Vale GT, Simplicio JA, Gonzaga NA, Yokota R, Ribeiro AA, Casarini DE, et al. Nebivolol prevents vascular oxidative stress and hypertension in rats chronically treated with ethanol. Atherosclerosis. 2018;274:67–76.
Ahmadian E, Khosroushahi AY, Eftekhari A, Farajnia S, Babaei H, Eghbal MA. Novel angiotensin receptor blocker, azilsartan induces oxidative stress and NFkB-mediated apoptosis in hepatocellular carcinoma cell line HepG2. Biomed Pharmacother. 2018;99:939–46.
Yang CS, Ho CT, Zhang J, Wan X, Zhang K, Lim J. Antioxidants: differing meanings in food science and health science. J Agric Food Chem. 2018;66:3063–68.
Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, et al. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr. 2008;87:142–49.
Morrison D, Hughes J, Della Gatta PA, Mason S, Lamon S, Russell AP, et al. Vitamin C and E supplementation prevents some of the cellular adaptations to endurance-training in humans. Free Radic Biol Med. 2015;89:852–62.
Merry TL, Ristow M. Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training? J Physiol. 2016;594:5135–47.
Johnson SA, Feresin RG, Navaei N, Figueroa A, Elam ML, Akhavan NS, et al. Effects of daily blueberry consumption on circulating biomarkers of oxidative stress, inflammation, and antioxidant defense in postmenopausal women with pre- and stage 1-hypertension: a randomized controlled trial. Food Funct. 2017;8:372–80.
Guo K, Lu J, Huang Y, Wu M, Zhang L, Yu H, et al. Protective role of PGC-1α in diabetic nephropathy is associated with the inhibition of ROS through mitochondrial dynamic remodeling. PLoS ONE. 2015;10:e0125176.
Zhang M, Brewer AC, Schröder K, Santos CX, Grieve DJ, Wang M, et al. NADPH oxidase-4 mediates protection against chronic load-induced stress in mouse hearts by enhancing angiogenesis. Proc Natl Acad Sci USA. 2010;107:18121–26.
Coughlan MT, Sharma K. Challenging the dogma of mitochondrial reactive oxygen species overproduction in diabetic kidney disease. Kidney Int. 2016;90:272–79.
Towler DA. Mitochondrial ROS deficiency and diabetic complications: AMP[K]-lifying the adaptation to hyperglycemia. J Clin Invest. 2013;123:4573–76.
Craige SM, Chen K, Pei Y, Li C, Huang X, Chen C, et al. NADPH oxidase 4 promotes endothelial angiogenesis through endothelial nitric oxide synthase activation. Circulation. 2011;124:731–40.
Brüll V, Burak C, Stoffel-Wagner B, Wolffram S, Nickenig G, Müller C, et al. Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial. Br J Nutr. 2015;114:1263–77.
Patel RV, Mistry BM, Shinde SK, Syed R, Singh V, Shin HS. Therapeutic potential of quercetin as a cardiovascular agent. Eur J Med Chem. 2018;155:889–904.
Tain YL, Lee WC, Wu KLH, Leu S, Chan JYH. Resveratrol prevents the development of hypertension programmed by maternal plus post-weaning high-fructose consumption through modulation of oxidative stress, nutrient-sensing signals, and gut microbiota. Mol Nutr Food Res. 2018:e1800066. https://doi.org/10.1002/mnfr.201800066.
Banday AA, Lokhandwala MF. Oxidative stress impairs cGMP-dependent protein kinase activation and vasodilator-stimulated phosphoprotein serine-phosphorylation. Clin Exp Hypertens. 2018;9:1–9.
Funding
These studies were supported in part by grants from the NIH, 5P01HL074940-11, 7R01DK039308-31, 5P01 HL068686-15, 5R01HL023081-35, and 2R01HL092196-10.
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Cuevas, S., Villar, V.A.M. & Jose, P.A. Genetic polymorphisms associated with reactive oxygen species and blood pressure regulation. Pharmacogenomics J 19, 315–336 (2019). https://doi.org/10.1038/s41397-019-0082-4
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DOI: https://doi.org/10.1038/s41397-019-0082-4
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