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  • Special Features - Renal Denervation and Sympathetic Nerve System
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Possible organ-protective effects of renal denervation: insights from basic studies

Hypertension Research volume 46, pages 2661–2669 (2023)Cite this article

Abstract

Inappropriate sympathetic nervous activation is the body’s response to biological stress and is thought to be involved in the development of various lifestyle-related diseases through an elevation in blood pressure. Experimental studies have shown that surgical renal denervation decreases blood pressure in hypertensive animals. Recently, minimally invasive catheter-based renal denervation has been clinically developed, which results in a reduction in blood pressure in patients with resistant hypertension. Accumulating evidence in basic studies has shown that renal denervation exerts beneficial effects on cardiovascular disease and chronic kidney disease. Interestingly, recent studies have also indicated that renal denervation improves glucose tolerance and inflammatory changes. In this review article, we summarize the evidence from animal studies to provide comprehensive insight into the organ-protective effects of renal denervation beyond changes in blood pressure.

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References

  1. Bromfield S, Muntner P. High blood pressure: the leading global burden of disease risk factor and the need for worldwide prevention programs. Curr Hypertens Rep. 2013;15:134.

    PubMed  PubMed Central  Google Scholar 

  2. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–23.

    PubMed  Google Scholar 

  3. Umemura S, Arima H, Arima S, Asayama K, Dohi Y, Hirooka Y, et al. The Japanese Society of hypertension guidelines for the management of hypertension (JSH 2019). Hypertens Res. 2019;42:9.

    Google Scholar 

  4. Berra E, Azizi M, Capron A, Høieggen A, Rabbia F, Kjeldsen SE, et al. Evaluation of adherence should become an integral part of assessment of patients with apparently treatment-resistant hypertension. Hypertension. 2016;68:297–306.

    CAS  PubMed  Google Scholar 

  5. Zanchetti A. From pathophysiology to therapeutic interventions: the span of hypertension research. J Hypertens. 2014;32:703–5.

    CAS  PubMed  Google Scholar 

  6. Katsurada K, Shinohara K, Aoki J, Nanto S, Kario K. Renal denervation: basic and clinical evidence. Hypertens Res. 2022;45:198–209.

    PubMed  Google Scholar 

  7. Moreira NJD, dos Santos F, Moreira ED, Farah D, de Souza LE, da Silva MB et al. Acute renal denervation normalizes aortic function and decreases blood pressure in spontaneously hypertensive rats. Sci Rep. 2020. https://doi.org/10.1038/S41598-020-78674-8.

  8. Peleli M, Flacker P, Zhuge Z, Gomez C, Wheelock CE, Persson AEG, et al. Renal denervation attenuates hypertension and renal dysfunction in a model of cardiovascular and renal disease, which is associated with reduced NADPH and xanthine oxidase activity. Redox Biol. 2017;13:522–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Ott C, Schmieder RE. Renal denervation for resistant hypertension: past, present, and future. Curr Hypertens Rep. 2015. https://doi.org/10.1007/S11906-015-0577-6.

    Article  PubMed  Google Scholar 

  10. Kario K, Yokoi Y, Okamura K, Fujihara M, Ogoyama Y, Yamamoto E, et al. Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial. Hypertens Res. 2022;45:221–31.

    PubMed  Google Scholar 

  11. Ogoyama Y, Tada K, Abe M, Nanto S, Shibata H, Mukoyama M et al. Effects of renal denervation on blood pressures in patients with hypertension: a systematic review and meta-analysis of randomized sham-controlled trials. Hypertens Res. 2022. https://doi.org/10.1038/s41440-021-00761-8.

  12. Kassab S, Kato T, Wilkins FC, Chen R, Hall JE, Granger JP. Renal denervation attenuates the sodium retention and hypertension associated with obesity. Hypertension. 1995;25:893–7.

    CAS  PubMed  Google Scholar 

  13. Canale MP, Manca Di Villahermosa S, Martino G, Rovella V, Noce A, De Lorenzo A, et al. Obesity-related metabolic syndrome: mechanisms of sympathetic overactivity. Int J Endocrinol. 2013. https://doi.org/10.1155/2013/865965.

  14. Henegar JR, Zhang Y, De Rama R, Hata C, Hall ME, Hall JE. Catheter-based radiorefrequency renal denervation lowers blood pressure in obese hypertensive dogs. Am J Hypertens. 2014;27:1285–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Osborn JW, Banek CT. Catheter-based renal nerve ablation as a novel hypertension therapy: lost, and then found, in translation. Hypertension. 2018;71:383–8.

    CAS  PubMed  Google Scholar 

  16. Schmieder RE. Renal denervation in patients with chronic kidney disease: current evidence and future perspectives. Nephrol Dial Transplant. 2022. https://doi.org/10.1093/NDT/GFAC189.

  17. Hering D, Esler MD, Schlaich MP. Chronic kidney disease: role of sympathetic nervous system activation and potential benefits of renal denervation. EuroIntervention. 2013;9:R127–35.

    PubMed  Google Scholar 

  18. Sanders MF, Blankestijn PJ. Chronic Kidney Disease as a potential indication for renal denervation. Front Physiol. 2016. https://doi.org/10.3389/FPHYS.2016.00220.

  19. Quarti-Trevano F, Seravalle G, Dell’Oro R, Mancia G, Grassi G. Autonomic cardiovascular alterations in chronic Kidney Disease: effects of dialysis, kidney transplantation, and renal denervation. Curr Hypertens Rep. 2021. https://doi.org/10.1007/S11906-021-01129-6.

  20. Campese VM, Kogosov E, Koss M. Renal afferent denervation prevents the progression of renal disease in the renal ablation model of chronic renal failure in the rat. Am J Kidney Dis. 1995;26:861–5.

    CAS  Google Scholar 

  21. Sata Y, Head GA, Denton K, May CN, Schlaich MP. Role of the sympathetic nervous system and its modulation in renal hypertension. Front Med (Lausanne). 2018. https://doi.org/10.3389/FMED.2018.00082.

  22. Singh RR, McArdle ZM, Iudica M, Easton LK, Booth LC, May CN, et al. Sustained decrease in blood pressure and reduced anatomical and functional reinnervation of renal nerves in hypertensive sheep 30 months after catheter-based renal denervation. Hypertension. 2019;73:718–27.

    CAS  PubMed  Google Scholar 

  23. Singh RR, McArdle ZM, Booth LC, May CN, Head GA, Moritz KM, et al. Increase in bioavailability of nitric oxide after renal denervation improves kidney function in sheep with hypertensive kidney disease. Hypertension. 2021;77:1299–310.

    CAS  PubMed  Google Scholar 

  24. Schäufele TG, Schlaich MP, Delles C, Klingbeil AU, Fleischmann EH, Schmieder RE. Impaired basal NO activity in patients with glomerular disease and the influence of oxidative stress. Kidney Int. 2006;70:1177–81.

    Google Scholar 

  25. Fine A, Penner B. The protective effect of cool dialysate is dependent on patients’ predialysis temperature. Am J Kidney Dis. 1996;28:262–5.

    CAS  PubMed  Google Scholar 

  26. Lutaif NA, Rocha EM, Veloso LA, Bento LM, Gontijo JAR. Renal contribution to thermolability in rats: role of renal nerves. Nephrol Dial Transpl. 2008;23:3798–805.

    CAS  Google Scholar 

  27. Durgam VR, Vitela M, Mifflin SW. Enhanced gamma-aminobutyric acid-B receptor agonist responses and mRNA within the nucleus of the solitary tract in hypertension. Hypertension. 1999;33:530–6.

    CAS  PubMed  Google Scholar 

  28. Ye S, Ozgur B, Campese VM. Renal afferent impulses, the posterior hypothalamus, and hypertension in rats with chronic renal failure. Kidney Int. 1997;51:722–7.

    CAS  PubMed  Google Scholar 

  29. Weiss ML, Chowdhury SI. The renal afferent pathways in the rat: a pseudorabies virus study. Brain Res. 1998;812:227–41.

    CAS  PubMed  Google Scholar 

  30. Patel KP, Xu B, Liu X, Sharma NM, Zheng H. Renal denervation improves exaggerated sympathoexcitation in rats with heart failure: a role for neuronal nitric oxide synthase in the paraventricular nucleus. Hypertension. 2016. https://doi.org/10.1161/HYPERTENSIONAHA.115.06794.

  31. Chen HH, Cheng PW, Ho WY, Lu PJ, Lai CC, Tseng YM, et al. Renal denervation improves the baroreflex and GABA system in chronic kidney disease-induced hypertension. Sci Rep. 2016. https://doi.org/10.1038/SREP38447.

  32. Seravalle G, Mancia G, Grassi G. Role of the sympathetic nervous system in hypertension and hypertension-related cardiovascular disease. High Blood Press Cardiovasc Prev. 2014;21:89–105.

    CAS  Google Scholar 

  33. Phillips JK. Pathogenesis of hypertension in renal failure: role of the sympathetic nervous system and renal afferents. Clin Exp Pharm Physiol. 2005;32:415–8.

    CAS  Google Scholar 

  34. Guild SJ, Barrett CJ, Malpas SC. Long-term recording of sympathetic nerve activity: the new frontier in understanding the development of hypertension? Clin Exp Pharm Physiol. 2005;32:433–9.

    CAS  Google Scholar 

  35. Malpas SC. Sympathetic nervous system overactivity and its role in the development of cardiovascular disease. Physiol Rev. 2010;90:513–57.

    CAS  Google Scholar 

  36. McHugh J, Keller NR, Appalsamy M, Thomas SA, Raj SR, Diedrich A, et al. Portal osmopressor mechanism linked to transient receptor potential vanilloid 4 and blood pressure control. Hypertension. 2010;55:1438–43.

    CAS  Google Scholar 

  37. Raj SR, Biaggioni I, Black BK, Rali A, Jordan J, Taneja I, et al. Sodium paradoxically reduces the gastropressor response in patients with orthostatic hypotension. Hypertension. 2006;48:329–34.

    CAS  Google Scholar 

  38. Jordan J, Shannon JR, Black BK, Ali Y, Farley M, Costa F, et al. The pressor response to water drinking in humans: a sympathetic reflex? Circulation. 2000;101:504–9.

    CAS  PubMed  Google Scholar 

  39. Mai TH, Garland EM, Diedrich A, Robertson D. Hepatic and renal mechanisms underlying the osmopressor response. Auton Neurosci. 2017;203:58–66.

    PubMed Central  Google Scholar 

  40. Johns EJ. Autonomic regulation of kidney function. Handb Clin Neurol. 2013;117:203–14.

    PubMed  Google Scholar 

  41. Schuetze KB, McKinsey TA, Long CS. Targeting cardiac fibroblasts to treat fibrosis of the heart: focus on HDACs. J Mol Cell Cardiol. 2014;70:100–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Hirayama Y, Saitoh H, Atarashi H, Hayakawa H. Electrical and mechanical alternans in canine myocardium in vivo. Depend Intracell calcium Cycl Circulation. 1993;88:2894–902.

    CAS  Google Scholar 

  43. Wilson LD, Jeyaraj D, Wan X, Hoeker GS, Said TH, Gittinger M, et al. Heart failure enhances susceptibility to arrhythmogenic cardiac alternans. Heart Rhythm. 2009;6:251–9.

    PubMed  Google Scholar 

  44. Hou Y, Hu J, Po SS, Wang H, Zhang L, Zhang F, et al. Catheter-based renal sympathetic denervation significantly inhibits atrial fibrillation induced by electrical stimulation of the left stellate ganglion and rapid atrial pacing. PLoS One. 2013. https://doi.org/10.1371/JOURNAL.PONE.0078218.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Hoffmann BA, Steven D, Willems S, Sydow K. Renal sympathetic denervation as an adjunct to catheter ablation for the treatment of ventricular electrical storm in the setting of acute myocardial infarction. J Cardiovasc Electrophysiol. 2013. https://doi.org/10.1111/JCE.12282.

    Article  PubMed  Google Scholar 

  46. Zipes DP, Rubart M. Neural modulation of cardiac arrhythmias and sudden cardiac death. Heart Rhythm. 2006;3:108–13.

    PubMed Central  Google Scholar 

  47. Gawałko M, Saljic A, Li N, Abu-Taha I, Jespersen T, Linz D, et al. Adiposity-associated atrial fibrillation: molecular determinants, mechanisms and clinical significance. Cardiovasc Res. 2022. https://doi.org/10.1093/CVR/CVAC093.

  48. Chang SN, Chang SH, Yu CC, Wu CK, Lai LP, Chiang FT, et al. Renal denervation decreases susceptibility to arrhythmogenic cardiac alternans and ventricular arrhythmia in a rat model of post-myocardial infarction heart failure. JACC Basic Transl Sci. 2017;2:184–93.

    PubMed  PubMed Central  Google Scholar 

  49. Jayachandran JV, Sih HJ, Winkle W, Zipes DP, Hutchins GD, Olgin JE. Atrial fibrillation produced by prolonged rapid atrial pacing is associated with heterogeneous changes in atrial sympathetic innervation. Circulation. 2000;101:1185–91.

    CAS  PubMed  Google Scholar 

  50. Linz D, Mahfoud F, Schotten U, Ukena C, Neuberger HR, Wirth K, et al. Renal sympathetic denervation suppresses postapneic blood pressure rises and atrial fibrillation in a model for sleep apnea. Hypertension. 2012;60:172–8.

    CAS  PubMed  Google Scholar 

  51. Zhao Q, Yu S, Zou M, Dai Z, Wang X, Xiao J, et al. Effect of renal sympathetic denervation on the inducibility of atrial fibrillation during rapid atrial pacing. J Inter Card Electrophysiol. 2012;35:119–25.

    Google Scholar 

  52. Rubart M, Zipes DP. Mechanisms of sudden cardiac death. J Clin Invest. 2005;115:2305–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Kochav SM, Garan H, Gorenstein LA, Wan EY, Yarmohammadi H. Cardiac sympathetic denervation for the management of ventricular arrhythmias. J Inter Card Electrophysiol. 2022;65:813–26.

    Google Scholar 

  54. Schwartz PJ, Motolese M, Pollavini G, Lotto A, Ruberti U, Trazzi R, et al. Prevention of sudden cardiac death after a first myocardial infarction by pharmacologic or surgical antiadrenergic interventions. J Cardiovasc Electrophysiol. 1992;3:2–16.

    Google Scholar 

  55. Collura CA, Johnson JN, Moir C, Ackerman MJ. Left cardiac sympathetic denervation for the treatment of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia using video-assisted thoracic surgery. Heart Rhythm. 2009;6:752–9.

    PubMed  Google Scholar 

  56. Pokorný J, Staněk V, Vrána M. Sudden cardiac death thirty years ago and at present. The role of autonomic disturbances in acute myocardial infarction revisited. Physiol Res. 2011;60:715–28.

    PubMed  Google Scholar 

  57. Coetzee WA, Opie LH. Effects of components of ischemia and metabolic inhibition on delayed afterdepolarizations in guinea pig papillary muscle. Circ Res. 1987;61:157–65.

    CAS  PubMed  Google Scholar 

  58. Wilson AL, Gandhi J, Suh Y, Joshi G, Smith NL, Khan SA. Renal innervation in resistant hypertension: a review of pathophysiology and renal denervation as potential treatment. Curr Hypertens Rev. 2020;16:115–27.

    PubMed  PubMed Central  Google Scholar 

  59. Linz D, Wirth K, Ukena C, Mahfoud F, Pöss J, Linz B, et al. Renal denervation suppresses ventricular arrhythmias during acute ventricular ischemia in pigs. Heart Rhythm. 2013;10:1525–30.

    PubMed  Google Scholar 

  60. Schotten U, Verheule S, Kirchhof P, Goette A. Pathophysiological mechanisms of atrial fibrillation: a translational appraisal. Physiol Rev. 2011;91:265–325.

    PubMed  Google Scholar 

  61. Ukena C, Mahfoud F, Spies A, Kindermann I, Linz D, Cremers B, et al. Effects of renal sympathetic denervation on heart rate and atrioventricular conduction in patients with resistant hypertension. Int J Cardiol. 2013;167:2846–51.

    PubMed  Google Scholar 

  62. Linz D, Mahfoud F, Schotten U, Ukena C, Hohl M, Neuberger HR, et al. Renal sympathetic denervation provides ventricular rate control but does not prevent atrial electrical remodeling during atrial fibrillation. Hypertension. 2013;61:225–31.

    CAS  Google Scholar 

  63. Jiang Z, Zhou X, Chen C, Wang Y, Fang P, Geng J, et al. Renal denervation for ventricular arrhythmia in patients with implantable cardioverter defibrillators. Int Heart J. 2018;59:328–32.

    PubMed  Google Scholar 

  64. Jiang W, Chen C, Huo J, Lu D, Jiang Z, Geng J et al. Comparison between renal denervation and metoprolol on the susceptibility of ventricular arrhythmias in rats with myocardial infarction. Sci Rep. 2018. https://doi.org/10.1038/S41598-018-28562-Z.

  65. Barajas L, Powers K, Wang P. Innervation of the renal cortical tubules: a quantitative study. Am J Physiol. 1984. https://doi.org/10.1152/AJPRENAL.1984.247.1.F50.

  66. DiBona GF, Sawin LL. Renal nerve activity in conscious rats during volume expansion and depletion. Am J Physiol. 1985. https://doi.org/10.1152/AJPRENAL.1985.248.1.F15.

  67. Morita H, Vatner SF. Effects of volume expansion on renal nerve activity, renal blood flow, and sodium and water excretion in conscious dogs. Am J Physiol. 1985. https://doi.org/10.1152/AJPRENAL.1985.249.5.F680.

  68. Heywood JT. The cardiorenal syndrome: lessons from the ADHERE database and treatment options. Heart Fail Rev. 2004;9:195–201.

    PubMed  Google Scholar 

  69. Willett I, Esler M, Burke F, Leonard P, Dudley F. Total and renal sympathetic nervous system activity in alcoholic cirrhosis. J Hepatol. 1985;1:639–48.

    CAS  PubMed  Google Scholar 

  70. Hasking GJ, Esler MD, Jennings GL, Burton D, Johns JA, Korner PI. Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation. 1986;73:615–21.

    CAS  PubMed  Google Scholar 

  71. Packer M. Activation and inhibition of sodium-hydrogen exchanger is a mechanism that links the pathophysiology and treatment of diabetes mellitus with that of heart failure. Circulation. 2017;136:1548–59.

    CAS  Google Scholar 

  72. Staahltoft D, Nielsen S, Janjua NR, Christensen S, Skøtt O, Marcussen N, et al. Losartan treatment normalizes renal sodium and water handling in rats with mild congestive heart failure. Am J Physiol Renal Physiol. 2002. https://doi.org/10.1152/AJPRENAL.00132.2001.

  73. Starklint J, Bech JN, Nyvad O, Jensen P, Pedersen EB. Increased urinary aquaporin-2 excretion in response to furosemide in patients with chronic heart failure. Scand J Clin Lab Invest. 2006;66:55–66.

    CAS  PubMed  Google Scholar 

  74. Huo JY, Jiang WY, Zhang SG, Lyu YT, Geng J, Chen M, et al. Renal denervation ameliorates cardiac metabolic remodeling in diabetic cardiomyopathy rats by suppressing renal SGLT2 expression. Lab Investig. 2022. https://doi.org/10.1038/s41374-021-00696-1.

  75. Patel KP, Katsurada K, Zheng H. Cardiorenal syndrome: the role of neural connections between the heart and the kidneys. Circ Res. 2022;130:1601–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Katsurada K, Nandi SS, Sharma NM, Patel KP. Enhanced expression and function of renal SGLT2 (Sodium-Glucose Cotransporter 2) in heart failure: role of renal nerves. Circ Heart Fail. 2021. https://doi.org/10.1161/CIRCHEARTFAILURE.121.008365.

  77. DiBona GF, Herman PJ, Sawin LL. Neural control of renal function in edema-forming states. Am J Physiol. 1988. https://doi.org/10.1152/AJPREGU.1988.254.6.R1017.

  78. DiBona GF, Sawin LL. Role of renal nerves in sodium retention of cirrhosis and congestive heart failure. Am J Physiol. 1991. https://doi.org/10.1152/AJPREGU.1991.260.2.R298.

  79. Torp M, Brønd L, Nielsen JB, Nielsen S, Christensen S, Jonassen TEN. Effects of renal denervation on the NKCC2 cotransporter in the thick ascending limb of the loop of Henle in rats with congestive heart failure. Acta Physiol (Oxf). 2012;204:451–9.

    CAS  PubMed  Google Scholar 

  80. Jonassen TEN, Marcussen N, Haugan K, Skyum H, Christensen S, Andreasen F, et al. Functional and structural changes in the thick ascending limb of Henle’s loop in rats with liver cirrhosis. Am J Physiol. 1997. https://doi.org/10.1152/AJPREGU.1997.273.2.R568.

  81. Barajas L, Powers K. Innervation of the renal proximal convoluted tubule of the rat. Am J Anat. 1989;186:378–88.

    CAS  PubMed  Google Scholar 

  82. Marumo R, Kaizuma S, Nogae S, Kanazawa M, Kimura T, Saito T, et al. Differential upregulation of rat Na-K-Cl cotransporter, rBSC1, mRNA in the thick ascending limb of Henle in different pathological conditions. Kidney Int. 1998;54:877–88.

    CAS  PubMed  Google Scholar 

  83. Nogae S, Michimata M, Kanazawa M, Honda S, Ohta M, Imai Y, et al. Cardiac infarcts increase sodium transporter transcripts (rBSC1) in the thick ascending limb of Henle. Kidney Int. 2000;57:2055–63.

    CAS  PubMed  Google Scholar 

  84. Jonassen TEN, Brønd L, Torp M, Græbe M, Nielsen S, Skøtt O, et al. Effects of renal denervation on tubular sodium handling in rats with CBL-induced liver cirrhosis. Am J Physiol Renal Physiol. 2003. https://doi.org/10.1152/AJPRENAL.00258.2002.

  85. Bao LZ, Shen M, Qudirat H, Shi JB, Su T, Song JW, et al. Obestatin ameliorates water retention in chronic heart failure by downregulating renal aquaporin 2 through GPR39, V2R and PPARG signaling. Life Sci. 2019. https://doi.org/10.1016/J.LFS.2019.05.049.

  86. Lai Y, Zhou H, Chen W, Liu H, Liu G, Xu Y, et al. The intrarenal blood pressure modulation system is differentially altered after renal denervation guided by different intensities of blood pressure responses. Hypertens Res. 2023;46:456–67.

    CAS  PubMed  Google Scholar 

  87. Zheng H, Liu X, Katsurada K, Patel KP. Renal denervation improves sodium excretion in rats with chronic heart failure: effects on expression of renal ENaC and AQP2. Am J Physiol Heart Circ Physiol. 2019;317:H958–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Turpie AGG, Bauer KA, Eriksson BI, Lassen MR. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002;162:1867–72.

    Google Scholar 

  89. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA. 1999;282:1523–9.

    CAS  Google Scholar 

  90. da Silva AA, do Carmo JM, Li X, Wang Z, Mouton AJ, Hall JE. Role of hyperinsulinemia and insulin resistance in hypertension: metabolic syndrome revisited. Can J Cardiol. 2020;36:671–82.

    PubMed  Google Scholar 

  91. Weidmann P, Böhlen L, De Courten M. Insulin resistance and hyperinsulinemia in hypertension. J Hypertens Suppl. 1995;13:S65–72.

    CAS  PubMed  Google Scholar 

  92. Smith MM, Minson CT. Obesity and adipokines: effects on sympathetic overactivity. J Physiol. 2012;590:1787–801.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Nazari S, Haghani M, Moosavi SMS. Bilateral renal denervation prevents the development of hypertension during diet-induced obesity in male rats. Exp Physiol. 2021;106:2248–61.

    CAS  PubMed  Google Scholar 

  94. Elliott RH, Matthews VB, Rudnicka C, Schlaich MP. Is it time to think about the sodium glucose co-transporter 2 sympathetically? Nephrology. 2016. https://doi.org/10.1111/nep.12620.

  95. Schlaich M, Straznicky N, Lambert E, Lambert G. Metabolic syndrome: a sympathetic disease? Lancet Diabetes Endocrinol. 2015. https://doi.org/10.1016/S2213-8587(14)70033-6.

  96. Rafiq K, Fujisawa Y, Sherajee SJ, Rahman A, Sufiun A, Kobori H, et al. Role of the renal sympathetic nerve in renal glucose metabolism during the development of type 2 diabetes in rats. Diabetologia. 2015. https://doi.org/10.1007/s00125-015-3771-9.

  97. Mahfoud F, Schlaich M, Kindermann I, Ukena C, Cremers B, Brandt MC, et al. Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: A pilot study. Circulation. 2011. https://doi.org/10.1161/CIRCULATIONAHA.110.991869.

  98. Chen W, Chang Y, He L, Jian X, Li L, Gao L, et al. Effect of renal sympathetic denervation on hepatic glucose metabolism and blood pressure in a rat model of insulin resistance. J Hypertens. 2016;34:2465–74.

    CAS  PubMed  Google Scholar 

  99. Pan T, Guo JH, Ling L, Qian Y, Dong YH, Yin HQ, et al. Effects of multi-electrode renal denervation on insulin sensitivity and glucose metabolism in a canine model of type 2 diabetes mellitus. J Vasc Inter Radio. 2018;29:731–8.

    Google Scholar 

  100. Harwani SC, Chapleau MW, Legge KL, Ballas ZK, Abboud FM. Neurohormonal modulation of the innate immune system is proinflammatory in the prehypertensive spontaneously hypertensive rat, a genetic model of essential hypertension. Circ Res. 2012;111:1190–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Norman RA, Dzielak DJ. Spontaneous hypertension is primarily the result of sympathetic overactivity and immunologic dysfunction. Proc Soc Exp Biol Med. 1986;182:448–53.

    PubMed  Google Scholar 

  102. Raikwar N, Braverman C, Snyder PM, Fenton RA, Meyerholz DK, Abboud FM, et al. Renal denervation and CD161a immune ablation prevent cholinergic hypertension and renal sodium retention. Am J Physiol Heart Circ Physiol. 2019;317:H517–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Xiao L, Kirabo A, Wu J, Saleh MA, Zhu L, Wang F, et al. Renal denervation prevents immune cell activation and renal inflammation in angiotensin II-induced hypertension. Circ Res. 2015;117:547–57.

    CAS  PubMed Central  Google Scholar 

  104. Yan X, Zhang QY, Zhang YL, Han X, Guo SB, Li HH. Gallic acid attenuates angiotensin II-induced hypertension and vascular dysfunction by inhibiting the degradation of endothelial nitric oxide synthase. Front Pharmacol. 2020. https://doi.org/10.3389/FPHAR.2020.01121.

  105. Liskova S. The organ-specific nitric oxide synthase activity in the interaction with sympathetic nerve activity: a hypothesis. Physiol Res. 2021;70:169–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Schrader LI, Kinzenbaw DA, Johnson AW, Faraci FM, Didion SP. IL-6 deficiency protects against angiotensin II induced endothelial dysfunction and hypertrophy. Arterioscler Thromb Vasc Biol. 2007;27:2576–81.

    CAS  Google Scholar 

  107. Pavlov VA, Tracey KJ. Neural regulation of immunity: molecular mechanisms and clinical translation. Nat Neurosci. 2017;20:156–66.

    CAS  PubMed  Google Scholar 

  108. Chen H, Wang R, Xu F, Zang T, Ji M, Yin J, et al. Renal denervation mitigates atherosclerosis in ApoE-/- mice via the suppression of inflammation. Am J Transl Res. 2020;12:5362–80.

    PubMed Central  Google Scholar 

  109. Beis D, Von Känel R, Heimgartner N, Zuccarella-Hackl C, Bürkle A, Ehlert U, et al. The role of norepinephrine and α-adrenergic receptors in acute stress-induced changes in granulocytes and monocytes. Psychosom Med. 2018;80:649–58.

    CAS  Google Scholar 

  110. Perez SD, Kozic B, Molinaro CA, Thyagarajan S, Ghamsary M, Lubahn CL, et al. Chronically lowering sympathetic activity protects sympathetic nerves in spleens from aging F344 rats. J Neuroimmunol. 2012;247:38–51.

    CAS  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Ellen Knapp, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This study was partially supported by the Japan Society for the Promotion of Science Grants in-Aid for Scientific Research (KAKENHI: 22H03514 and 22K19712 to AN).

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Steeve Akumwami

  2. Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Steeve Akumwami & Akira Nishiyama

  3. Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Asahiro Morishita & Hideki Kobara

  4. Department of Surgery, Kamenge Military Hospital, Bujumbura, Burundi

    Achille Iradukunda

Authors
  1. Steeve Akumwami
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  2. Asahiro Morishita
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  3. Achille Iradukunda
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  4. Hideki Kobara
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  5. Akira Nishiyama
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Correspondence to Akira Nishiyama.

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Akumwami, S., Morishita, A., Iradukunda, A. et al. Possible organ-protective effects of renal denervation: insights from basic studies. Hypertens Res 46, 2661–2669 (2023). https://doi.org/10.1038/s41440-023-01393-w

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  • DOI: https://doi.org/10.1038/s41440-023-01393-w

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