Abstract
The sympathetic nervous system plays an important role in circulatory and metabolic control and has clearly been established as a major contributor to the development of hypertension, as elevated sympathetic nerve activity initiates and sustains the elevation of blood pressure. Increased sympathetic outflow to the heart, resulting in increased cardiac output and neurally mediated vasoconstriction of peripheral blood vessels, is an obvious example of a neural pathophysiologic pathway leading to elevated blood pressure. The consequences of increased sympathetic outflow to the kidneys, perhaps most important in this context, are sodium and water retention, increased renin release, and alterations of renal blood flow—effects that contribute substantially to both acute and long-term blood pressure elevations. Accordingly, renal sympathetic nerve ablation appears to be a logical therapeutic approach for the treatment of hypertension. Recent reports on a novel catheter-based renal nerve ablation procedure reviewed in this article are promising.
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Perkovic V, Huxley R, Wu Y, et al.: The burden of blood pressure-related disease: a neglected priority for global health. Hypertension 2007, 50(6):991–997.
Kearney PM, Whelton M, Reynolds K, et al.: Global burden of hypertension: analysis of worldwide data. Lancet 2005, 365(9455):217–223.
DiBona GF: The sympathetic nervous system and hypertension: recent developments. Hypertension 2004, 43(2):147–150.
DiBona GF, Kopp UC: Neural control of renal function. Physiol Rev 1997, 77(1):75–197.
Alexander BT, Hendon AE, Ferril G, Dwyer TM: Renal denervation abolishes hypertension in low-birth-weight offspring from pregnant rats with reduced uterine perfusion. Hypertension 2005, 45(4):754–758.
Kassab S, Kato T, Wilkins FC, et al.: Renal denervation attenuates the sodium retention and hypertension associated with obesity. Hypertension 1995, 25(4 Pt 2):893–897.
Smithwick RH, Thompson JE: Splanchnicectomy for essential hypertension; results in 1,266 cases. J Am Med Assoc 1953, 152(16):1501–1504.
Morrissey DM, Brookes VS, Cooke WT: Sympathectomy in the treatment of hypertension, review of 122 cases. Lancet 1953, 1(6757):403–408.
Esler M, Jennings G, Biviano B, et al.: Mechanism of elevated plasma noradrenaline in the course of essential hypertension. J Cardiovasc Pharmacol 1986, 8(Suppl 5):S39–S43.
Schlaich MP, Lambert E, Kaye DM, et al.: Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and angiotensin neuromodulation. Hypertension 2004, 43(2):169–175.
Esler M, Jennings G, Lambert G: Noradrenaline release and the pathophysiology of primary human hypertension. Am J Hypertens 1989, 2(3 Pt 2):140 S–146 S.
Hasking GJ, Esler MD, Jennings GL, et al.: Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation 1986, 73(4):615–621.
Aggarwal A, Esler MD, Morris MJ, et al.: Regional sympathetic effects of low-dose clonidine in heart failure. Hypertension 2003, 41(3):553–557.
Petersson M, Friberg P, Eisenhofer G, et al.: Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure. Eur Heart J 2005, 26(9):906–913.
Barajas L: Innervation of the renal cortex. Fed Proc 1978, 37(5):1192–1201.
Bell-Reuss E, Trevino DL, Gottschalk CW: Effect of renal sympathetic nerve stimulation on proximal water and sodium reabsorption. J Clin Invest 1976, 57(4):1104–1107.
Kirchheim H, Ehmke H, Persson P: Sympathetic modulation of renal hemodynamics, renin release and sodium excretion. Klin Wochenschr 1989, 67(17):858–864.
Kon V: Neural control of renal circulation. Miner Electrolyte Metab 1989, 15(1–2):33–43.
Zanchetti AS: Neural regulation of renin release: experimental evidence and clinical implications in arterial hypertension. Circulation 1977, 56(5):691–698.
Campese VM: Neurogenic factors and hypertension in chronic renal failure. J Nephrol 1997, 10(4):184–187.
Ye S, Gamburd M, Mozayeni P, et al.: A limited renal injury may cause a permanent form of neurogenic hypertension. Am J Hypertens 1998, 11(6 Pt 1):723–728.
Ye S, Zhong H, Yanamadala V, Campese VM: Renal injury caused by intrarenal injection of phenol increases afferent and efferent renal sympathetic nerve activity. Am J Hypertens 2002, 15(8):717–724.
Campese VM: Neurogenic factors and hypertension in renal disease. Kidney Int 2000, 57(Suppl 75):S2–S6.
Campese VM, Kogosov E: Renal afferent denervation prevents hypertension in rats with chronic renal failure. Hypertension 1995, 25(4 Pt 2):878–882.
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(5):861–865.
DiBona GF: Sympathetic nervous system and the kidney in hypertension. Curr Opin Nephrol Hypertens 2002, 11(2):197–200.
DiBona GF: Neural control of the kidney: past, present, and future. Hypertension 2003, 41(3 Pt 2):621–624.
Fajardo J, Lopez-Novoa JM: Effect of chemical sympathectomy on renal hydroelectrolytic handling in dogs with chronic caval constriction. Clin Physiol Biochem 1986, 4(4):252–256.
Norman RA Jr, Murphy WR, Dzielak DJ, et al.: Role of the renal nerves in one-kidney, one clip hypertension in rats. Hypertension 1984, 6(5):622–626.
Joles JA, Koomans HA: Causes and consequences of increased sympathetic activity in renal disease. Hypertension 2004, 43(4):699–706.
Mailloux LU, Haley WE: Hypertension in the ESRD patient: pathophysiology, therapy, outcomes, and future directions. Am J Kidney Dis 1998, 32(5):705–719.
Ritz E, Rychlik I, Locatelli F, Halimi S: End-stage renal failure in type 2 diabetes: a medical catastrophe of worldwide dimensions. Am J Kidney Dis 1999, 34(5):795–808.
Klag MJ, Whelton PK, Randall BL, et al.: Blood pressure and end-stage renal disease in men. N Engl J Med 1996, 334(1):13–18.
Rostand SG, Brunzell JD, Cannon RO 3rd, Victor RG: Cardiovascular complications in renal failure. J Am Soc Nephrol 1991, 2(6):1053–1062.
Herzog CA, Ma JZ, Collins AJ: Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med 1998, 339(12):799–805.
Coresh J, Wei GL, McQuillan G, 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(9):1207–1216.
Tonelli M, Bohm C, Pandeya S, et al.: Cardiac risk factors and the use of cardioprotective medications in patients with chronic renal insufficiency. Am J Kidney Dis 2001, 37(3):484–489.
Lazarus JM, Hampers C, Merrill JP: Hypertension in chronic renal failure. Treatment with hemodialysis and nephrectomy. Arch Intern Med 1974, 133(6):1059–1066.
Ligtenberg G, Blankestijn PJ, Oey PL, et al.: Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N Engl J Med 1999, 340(17):1321–1328.
Grassi G, Seravalle G, Colombo M, et al.: Body weight reduction, sympathetic nerve traffic, and arterial baroreflex in obese normotensive humans. Circulation 1998, 97(20):2037–2042.
Narkiewicz K, Pesek CA, Kato M, et al.: Baroreflex control of sympathetic nerve activity and heart rate in obstructive sleep apnea. Hypertension 1998, 32(6):1039–1043.
Schobel HP, Fischer T, Heuszer K, et al.: Preeclampsia—a state of sympathetic overactivity. N Engl J Med 1996, 335(20):1480–1485.
Zoccali C, Mallamaci F, Parlongo S, et al.: Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease. Circulation 2002, 105(11):1354–1359.
Vonend O, Marsalek P, Russ H, et al.: Moxonidine treatment of hypertensive patients with advanced renal failure. J Hypertens 2003, 21(9):1709–1717.
Strojek K, Grzeszczak W, Gorska J, et al.: Lowering of microalbuminuria in diabetic patients by a sympathicoplegic agent: novel approach to prevent progression of diabetic nephropathy? J Am Soc Nephrol 2001, 12(3):602–605.
Onesti G, Kim KE, Greco JA, et al.: Blood pressure regulation in end-stage renal disease and anephric man. Circ Res 1975, 36(6 Suppl 1):145–152.
Getts RT, Hazlett SM, Sharma SB, et al.: Regression of left ventricular hypertrophy after bilateral nephrectomy. Nephrol Dial Transplant 2006, 21(4):1089–1091.
Schlaich MP, Kaye DM, Lambert E, et al.: Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation 2003, 108(5):560–565.
•• Krum H, Schlaich M, Whitbourn R, et al.: Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 2009, 373(9671):1275–1281. This study presents the first data on the safety and efficacy of a novel catheter-based approach to functionally denervate the human kidney, demonstrating a favorable safety profile and substantial and sustained reductions in blood pressure.
•• Schlaich MP, Sobotka PA, Krum H, et al.: Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med 2009, 361(9):932–934. This study reports on a patient treated with catheter-based renal nerve ablation, demonstrating a reduction in central sympathetic outflow indicative of a potential involvement of afferent nerve fibers in the sustained blood pressure reduction associated with the procedure.
Disclosure
Dr. Sobotka is an employee of Ardian, Inc.; Dr. Schlaich and Dr. Krum are principal investigators in clinical trials sponsored by Ardian, Inc. (NCT00483808 and NCT00551304 at http://ClinicalTrials.gov). Dr. Schlaich is supported by a Senior Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia.
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Schlaich, M.P., Krum, H. & Sobotka, P.A. Renal Sympathetic Nerve Ablation: The New Frontier in the Treatment of Hypertension. Current Science Inc 12, 39–46 (2010). https://doi.org/10.1007/s11906-009-0078-6
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DOI: https://doi.org/10.1007/s11906-009-0078-6