Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Effect of ACE inhibitors and β-blockers on homocysteine levels in essential hypertension

Journal of Human Hypertension volume 22, pages 289–294 (2008)Cite this article

Abstract

Recent studies have shown that antihypertensive drugs like diuretics increase plasma homocysteine (Hcy) levels. However, the effect of other antihypertensive drugs on plasma Hcy levels has not been tested extensively. The aim of present study was to investigate the effect of antihypertensive therapy (AHT) on Hcy levels in essential hypertensive subjects. A case–control study of 273 patients with essential hypertension (EH) and 103 normotensive controls was undertaken. Plasma Hcy levels were measured before and after 6 weeks of AHT. The genotyping of MTHFR C677T polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. Angiotensin-converting enzyme (ACE) inhibitors and β-blockers significantly decreased and hydrochlorothiazides significantly increased the plasma Hcy levels in hypertensive patients (P<0.05). No significant association between MTHFR C677T genotypes and changes in Hcy levels in response to antihypertensive was observed in EH patients. The decrease in Hcy induced by β-blockers and ACE inhibitors observed in our study may be due to the improvement of endothelial function along with improved renal function. Thus, our results suggest that ACE inhibitors and β-blockers may provide additional beneficial therapeutic effects to the EH patients by decreasing Hcy levels.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Gupta R . Trends in hypertension epidemiology in India. J Hum Hypertens 2004; 18: 73–78.

    Article  CAS  PubMed  Google Scholar 

  2. Chaturvedi S, Pant M, Neelam, Yadav G . Hypertension in Delhi: prevalence, awareness, treatment and control. Trop Doct 2007; 37: 142–145.

    Article  CAS  PubMed  Google Scholar 

  3. Singh RB, Beegom R, Mehta AS, Niaz MA, De AK, Haque M et al. Prevalence and risk factors of hypertension and age specific blood pressures in five cities; a study in Indian women. NKP Salve Institute of Medical Sciences, Nagpur, India. Five City Study Group. Int J Cardiol 1998; 63: 165–173.

    Article  CAS  PubMed  Google Scholar 

  4. Coresh J, Wei GL, McQuillan G, Brancati FL, Levey AS, Jones C et al. Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988–1994). Arch Intern Med 2001; 161: 1207–1216.

    Article  CAS  PubMed  Google Scholar 

  5. Lim U, Cassano PA . Homocysteine and blood pressure in the third National Health and Nutrition Examination Survey. Am J Epidemiol 2002; 156: 1105–1113.

    Article  PubMed  Google Scholar 

  6. Nygard O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehaug JE et al. Total plasma homocysteine and cardiovascular risk profile, The Hordaland Homocysteine study. JAMA 1995; 274: 1526–1533.

    Article  CAS  PubMed  Google Scholar 

  7. Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J . Determinants of plasma total homocysteine concentration in the Framingham offspring cohort. Am J Clin Nutr 2001; 73: 613–621.

    Article  CAS  PubMed  Google Scholar 

  8. Kahleova R, Palyzova D, Zvara K, Zvárová J, Hrach K, Nováková I et al. Essential hypertension in adolescents: association with insulin resistance and with metabolism of homocysteine and vitamins. Am J Hypertens 2002; 15: 857–864.

    Article  CAS  PubMed  Google Scholar 

  9. Sutton-Tyrrell K, Bostom A, Selhub J, Zeigler-Johnson C . High homocysteine levels are independently related to isolated systolic hypertension in older adults. Circulation 1997; 96: 1745–1749.

    Article  CAS  PubMed  Google Scholar 

  10. Lip GY, Edmunds E, Martin SC, Jones AF, Blann AD, Beevers DG . A pilot study of homocyst(e)ine levels in essential hypertension: relationship to von Willebrand factor, an index of endothelial damage. Am J Hypertens 2001; 14: 627–631.

    Article  CAS  PubMed  Google Scholar 

  11. Sheu WH, Lee WJ, Chen YT . Plasma homocysteine concentrations and insulin sensitivity in hypertensive subjects. Am J Hypertens 2000; 13: 14–20.

    Article  CAS  PubMed  Google Scholar 

  12. Neugebauer S, Tarnow L, Stehouwer C, Teerlink T, Baba T, Watanabe T et al. Total plasma homocysteine is associated with hypertension in type I diabetic patients. Diabetologia 2002; 45: 1315–1324.

    Article  CAS  PubMed  Google Scholar 

  13. van Guldener C, Nanayakkara PW, Stehouwer CD . Homocysteine and blood pressure. Curr Hypertens Rep 2003; 5: 26–31.

    Article  PubMed  Google Scholar 

  14. Sundstrom J, Sullivan L, D'Agostino RB, Jacques PF, Selhub J, Rosenberg IH et al. Plasma homocysteine, hypertension incidence, and blood pressure tracking: the Framingham Heart study. Hypertension 2003; 42: 1100–1105.

    Article  PubMed  Google Scholar 

  15. Pierdomenico SD, Bucci A, Lapenna D, Lattanzio FM, Talone L, Cuccurullo F et al. Circulating homocysteine levels in sustained and white coat hypertension. J Hum Hypertens 2003; 17: 165–170.

    Article  CAS  PubMed  Google Scholar 

  16. Rolland PH, Friggi A, Barlatier A, Piquet P, Latrille V, Faye MM et al. Hyperhomocysteinemia-induced vascular damage in the mini pig: captopril-hydrochlorothiazide combination prevents elastic alterations. Circulation 1995; 91: 1161–1174.

    Article  CAS  PubMed  Google Scholar 

  17. Curgunlu A, Karter Y, Uzun H, Aydin S, Erturk N, Vehid S et al. Hyperhomocysteinemia: an additional risk factor in white coat hypertension. Int Heart J 2005; 46: 245–254.

    Article  CAS  PubMed  Google Scholar 

  18. Jain S, Ram H, Kumari S, Khullar M . Plasma homocysteine levels in Indian patients with essential hypertension and their siblings. Ren Fail 2003; 25: 195–201.

    Article  CAS  PubMed  Google Scholar 

  19. Ueland PM, Refsum H . Plasma homocysteine, a risk factor for vascular disease: plasma levels in health, disease, and drug therapy. J Lab Clin Med 1989; 114: 473–501.

    CAS  PubMed  Google Scholar 

  20. Desouza C, Keebler M, McNamara DB, Fonseca V . Drugs affecting homocysteine metabolism: impact on cardiovascular risk. Drugs 2002; 62: 605–616.

    Article  CAS  PubMed  Google Scholar 

  21. Morrow LE, Grimsley EW . Long-term diuretic therapy in hypertensive patients: effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations. South Med J 1999; 92: 866–870.

    Article  CAS  PubMed  Google Scholar 

  22. Westphal S, Rading A, Luley C, Dierkes J . Antihypertensive treatment and homocysteine concentrations. Metabolism 2003; 52: 261–263.

    Article  CAS  PubMed  Google Scholar 

  23. Chobanian AV, Bakris GL, Black HR, Green LA, Izzo Jr JL, Jones DW et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206–1252.

    Article  CAS  PubMed  Google Scholar 

  24. Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH et al. Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA 2003; 289: 2534–2544.

    Article  CAS  PubMed  Google Scholar 

  25. Jonkers IJ, de Man FH, Onkenhout W, van der Laarse A, Smelt AH . Implication of fibrate therapy for homocysteine. Lancet 1999; 354: 1208.

    Article  CAS  PubMed  Google Scholar 

  26. Atar I, Korkmaz ME, Demircan S, Atar IA, Bozbas H, Aydinalp A et al. Beta blocker effects on plasma homocysteinepatients with hypertension. Atherosclerosis 2005; 2: 399–402.

    Article  Google Scholar 

  27. Korkmaz ME, Atar I, Tayfun E, Yildirir A, Ulucam M, Ozin B et al. Effects of a betablocker and spironolactone on plasma homocysteine levels. Int J Cardiol 2003; 88: 119–120.

    Article  PubMed  Google Scholar 

  28. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII). JAMA 2003; 289: 2560–2572.

    Article  Google Scholar 

  29. Lahiri DK, Nurnberger Jr JL . A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acid Res 1991; 19: 5444.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG et al. A candidate genetic risk factor for vascular disease: a common mutation in, methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111–113.

    Article  CAS  PubMed  Google Scholar 

  31. Wong PC, Hart SD, Duncia JV, Timmermans PB . Nonpeptide angiotensin II receptor antagonists. Studies with DuP 753 and EXP3174 in dogs. Eur J Pharmacol 1991; 202: 323–330.

    Article  CAS  PubMed  Google Scholar 

  32. Imai T, Hirata Y, Emori T, Yanagisawa M, Masaki T, Marumo F . Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells. Hypertension 1992; 19: 753–757.

    Article  CAS  PubMed  Google Scholar 

  33. Hahn AW, Resink TJ, Scott-Burden T, Powell J, Dohi Y, Buhler FR . Stimulation of endothelin mRNA and secretion in rat vascular smooth muscle cells, a novel autocrine function. Cell Regul 1990; 1: 649–659.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Nagy L, Tarjan J, Samoczi M, Kovacs I, Takacs J . Effect of benazepril on endothelial function in previously untreated hypertensive patients. The Working Group of Cardiology of the Academic Committee of Veszprem, Hungary. Am J Ther 1998; 5: 233–236.

    Article  CAS  PubMed  Google Scholar 

  35. Tschudi MR, Criscione L, Novosel D, Pfeiffer K, Luscher TF . Antihypertensive therapy augments endothelium-dependent relaxations in coronary arteries of spontaneously hypertensive rats. Circulation 1994; 89: 2212–2218.

    Article  CAS  PubMed  Google Scholar 

  36. Tawakol A, Omland T, Gerhard M, Wu JT, Creager MA . Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilatation in humans. Circulation 1997; 95: 1119–1121.

    Article  CAS  PubMed  Google Scholar 

  37. Tyagi SC, Smiley LM, Mujumdar VS . Homocyst(e)ine impairs endocardial endothelial function. Can J Physiol Pharm 1999; 77: 950–957.

    Article  CAS  Google Scholar 

  38. Bonaventura D, Tirapelli CR, Haddad R, Hoehr NF, Eberlin MN, De Oliveira AM . Chronic methionine load-induced hyperhomocysteinemia enhances rat carotid responsiveness for angiotensin II. Pharmacology 2004; 70: 91–99.

    Article  CAS  PubMed  Google Scholar 

  39. Jiang S, Hsu YH, Niu T, Xu X, Xing H, Chen C et al. A common haplotype on methylenetetrahydrofolate reductase gene modifies the effect of angiotensin-converting enzyme inhibitor on blood pressure in essential hypertension patients—a family-based association study. Clin Exp Hypertens 2005; 6: 509–521.

    Article  Google Scholar 

  40. Sharabi Y, Doolman R, Rosenthal T, Grossman E, Rachima-Maoz C, Nussinovitch N et al. Homocysteine levels in hypertensive patients with a history of cardiac or cerebral atherothrombotic events. Am J Hypertens 1999; 12: 766–771.

    Article  CAS  PubMed  Google Scholar 

  41. Do KQ, Benz B, Sorg O, Pellerin L, Magistretti PJ . Beta-adrenergic stimulation promotes homocysteinic acid release from astrocyte cultures: evidence for a role of astrocytes in the modulation of synaptic transmission. J Neurochem 1997; 68: 2386–2394.

    Article  CAS  PubMed  Google Scholar 

  42. Basu TK, Mann S . Vitamin B-6 normalizes the altered sulfur amino acid status of rats fed diets containing pharmacological levels of niacin without reducing niacin's hypolipidemic effects. J Nutr 1997; 127: 117–121.

    Article  CAS  PubMed  Google Scholar 

  43. Selhub J . The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. J Nutr 2006; 136: 1726S–1730S.

    Article  CAS  PubMed  Google Scholar 

  44. Mora S, Cook N, Buring JE, Ridker PM, Lee IM . Physical activity and reduced risk of cardiovascular events. Potential mediating mechanisms. Circulation 2007; 16: 2110–2118.

    Article  Google Scholar 

  45. Sotgia S, Carru C, Caria MA, Tadolini B, Deiana L, Zinellu A . Acute variations in homocysteine levels are related to creatine changes induced by physical activity. Clin Nutr 2007; 26: 444–449.

    Article  CAS  PubMed  Google Scholar 

  46. Kumar J, Das SK, Sharma P, Karthikeyan G, Ramakrishnan L, Sengupta S . Homocysteine levels are associated with MTHFR A1298C polymorphism in Indian population. J Hum Genet 2005; 50: 655–663.

    Article  CAS  PubMed  Google Scholar 

  47. Markan S, Sachdeva M, Sehrawat BS, Kumari S, Jain S, Khullar M . MTHFR 677 CT/MTHFR 1298 CC genotypes are associated with increased risk of hypertension in Indians. Mol Cell Biochem 2007; 302: 125–131.

    Article  CAS  PubMed  Google Scholar 

  48. Dierkes J, Westphal S . Effect of drugs on homocysteine concentrations. Semin Vasc Med 2005; 5: 124–139.

    Article  PubMed  Google Scholar 

  49. Schelleman H, Stricker BH, Verschuren WM, de Boer A, Kroon AA, de Leeuw PW et al. Interactions between five candidate genes and antihypertensive drug therapy on blood pressure. Pharmacogenomics 2006; 6: 22–26.

    Article  CAS  Google Scholar 

  50. Westphal S, Rading A, Luley C, Dierkes J . Antihypertensive treatment and homocysteine concentrations. Metabolism 2003; 52: 261–263.

    Article  CAS  PubMed  Google Scholar 

  51. Freis ED . The efficacy and safety of diuretics in treating hypertension. Ann Intern Med 1995; 122: 223–226.

    Article  CAS  PubMed  Google Scholar 

  52. Muda P, Kampus P, Zilmer M, Ristimäe T, Fischer K, Zilmer K et al. Effect of antihypertensive treatment with candesartan or amlodipine on glutathione and its redox status, homocysteine and vitamin concentrations in patients with essential hypertension. J Hypertens 2005; 23: 105–112.

    Article  CAS  PubMed  Google Scholar 

  53. Inamoto N, Katsuya T, Kokubo Y, Mannami T, Asai T, Baba S et al. Association of methylenetetrahydrofolate reductase gene polymorphism with carotid atherosclerosis depending on smoking status in a Japanese general population. Stroke 2003; 34: 1628–1633.

    Article  CAS  PubMed  Google Scholar 

  54. Stephanie H, Fabien M, Rod A, Micky O, Lofti T, Lyn RG . The methylentetrahydrofolate reductase gene variant (C677T) as a risk factor for essential hypertension in Caucasians. Hypertens Res 2004; 27: 663–667.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    A Poduri, J Kaur & M Khullar

  2. Department of Community Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    J S Thakur

  3. Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    S Kumari & S Jain

Authors
  1. A Poduri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J S Thakur
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Kumari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Khullar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Khullar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Poduri, A., Kaur, J., Thakur, J. et al. Effect of ACE inhibitors and β-blockers on homocysteine levels in essential hypertension. J Hum Hypertens 22, 289–294 (2008). https://doi.org/10.1038/sj.jhh.1002325

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1002325

Keywords

This article is cited by

Search

Advanced search

Quick links