Abstract
Hypertension is very common in patients with chronic renal failure and contributes to cardiovascular morbidity and mortality. Several mechanisms may contribute to hypertension in these patients, but recently a large body of evidence supports the notion that activation of the sympathetic nervous system (SNS) may play a very important role. In rats with 5/6 nephrectomy, the turnover rate of norepinephrine was increased in brain nuclei involved in the noradrenergic control of blood pressure, and dorsal rhizotomy prevented hypertension. Studies in human subjects with chronic renal failure and hypertension have also shown increased peripheral SNS activity measured my microneurography in the peroneal nerve and normalization with nephrectomy. In all, these studies indicate that renal injuries may activate renal afferent pathways that connect with integrative brain structures in SNS activity and blood pressure. We have also shown that central SNS activity is modulated by local expression of nitric oxide, which, in turn, is regulated by interleukin-1â.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References and Recommended Reading
Campese V, MozaYeni P: Pathophysiology of hypertension in specific renal parenchymal diseases. In Clinical Nephrology, Dialysis and Transplantation. Edited by Malluche HH, Sawaya BP, Hakim RM, Sayegh MH. Dusti-Verlag Dr. Karl Feiste; 1999:7–12.
Galla JH, Luke RG: Hypertension in renal parenchymal disease. In The Kidney. Edited by Brenner BM, Rector FC. Philadelphia:WB Saunders Company; 2000:2035–2058.
Klag MJ, Whelton PK, Randall BL, et al.: Blood pressure and end-stage renal disease in men. N Engl J Med 1996, 334:13–18.
Curtis JR, Eastwood JB, Smith EK: Maintenance hemodialysis. Q J Med 1969, 38:49–89.
Schalekamp MADH, Schalekamp-Kuyken MPA, Demoor- Fruytier M, et al.: Interrelationships between blood pressure, renin, renin substrate and blood, in terminal renal failure. Clin Sci Mol Med 1973, 45:417–428.
Lazarus JM, Hampers CL, Merrill JP: Hypertension in chronic renal failure. Treatment with hemodialysis and nephrectomy. Arch Intern Med 1974, 133:1059–1066.
Atuk NO, Bailey CJ, Turner S, et al.: Red blood cell catechol-omethyl transferase, plasma catecholamines and renin in renal failure. Trans Am Soc Artif Intern Organs 1976, 22:195–200.
Lake CR, Ziegler MG, Coleman MD, Kopin IJ: Plasma levels of norepinephrine and dopamine-beta-hydroxylase in CRF patients treated with dialysis. Cardiovasc Med 1979, 1:1099–1111.
Henrich WL, Katz FH, Molinoff PB, Schrier RW: Competitive effects of hypokalemia and, depletion on plasma renin activity, aldosterone and catecholamine concentrations in hemodialysis patients. Kidney Int 1977, 12:279–284.
Izzo JL, Izzo MS, Sterns RH, Freeman RB: Sympathetic nervous system hyperactivity in maintenance hemodialysis patients. Trans Am Soc Artif Organs 1982, 28:604–607.
Cuche JL, Prinseau J, Selz F, et al.: Plasma free, sulfo- and glucuro-conjugated catecholamines in uremic patients. Kidney Int 1986, 30:566–572.
Campese VM, Romoff MS, Levitan D, et al.: Mechanisms of autonomic nervous system dysfunction in uremia. Kidney Int 1981, 20:246–253.
Ishii M, Ikeda T, Takagi M: Elevated plasma catecholamines in hypertensives with primary glomerular diseases. Hypertension 1983, 5:545–551.
Converse RL, Jacobsen TN, Toto RD, et al.: Sympathetic overactivity in patients with CRF. N Engl J Med 1992, 327:1912–1918. This is the first direct demonstration that peripheral SNS activity, measured by microneurography in the peroneal nerve, is increased in patients with end-stage renal disease on maintenance hemodialysis.
Ye S, Ozgur B, Campese VM: Renal afferent impulses, the posterior hypothalamus, and hypertension in rats with chronic renal failure. Kidney Int 1997, 51:722–727. This is the first study to demonstrate that a renal injury caused by intrarenal injection of phenol causes a neurogenic form of hypertension due to activation of central integrative pathways of the SNS. Renal denervation prevented this form of hypertension.
Bigazzi R, Kogosov E, Campese VM: Altered norepinephrine turnover in the brain of rats with chronic renal failure. J Am Soc Nephrol 1994, 4:1901–1907.
Recordati G, Moss NG, Genovisi S, Rogenes P: Renal chemoreceptors. J Auton Nerv Syst 1981, 3:237–251.
Katholi RE: Renal nerves and hypertension: an update. Fed Proc 1985, 44:2846–2850.
Dibona GF: The function of the renal nerves. Rev Physiol Biochem Pharmacol 1982, 94:75–181.
Calaresu FR, Ciriello J: Renal afferent nerves affect discharge rate of medullary and hypothalamic single units in cat. J Auton Nerv Syst 1981, 3:311–320.
Ciriello J, Calaresu FR: Central projection of afferent renal fibers in the rat: an anterograde transport study of horseradish peroxidase. J Auton Nerv Syst 1983, 8:273–285. This study established for the first time the existence of a connection between efferent renal fibers and central integrative structure involved in the noradrenergic control of blood pressure.
Katholi RE, Whitlow PL, Hageman GR, Woods T: Intrarenal adenosine produces hypertension by activating the sympathetic nervous system via the renal nerves. J Hypertens 1984, 2:349–359.
Katholi RE, Winternitz SR, Oparil S: Decrease in peripheral sympathetic nervous system activity following renal denervation or uncapping in the one-kidney one-clip Goldblatt hypertensive rat. J Clin Invest 1982, 69:55–62.
Brody MJ, Johnson AK: Role of the anteroventral third ventricle region in fluid and electrolyte balance, arterial pressure regulation and hypertension. In Frontiers in Neuroendocrinology. Edited by Ganong WF. New York: Raven Press; 1980:249–292.
Wyss JM, Aboukarsh N, Oparil S: Sensory denervation of the kidney attenuates renovascular hypertension in the rat. Am J Physiol 1986, 19:H82-H86.
Katholi RE, Naftilan AJ, Oparil S: Importance of renal sympathetic tone in the development of DOCA-salt hypertension in rat. Hypertension 1980, 2:266–273.
Katholi RE, Winternitz SR, Oparil S: Role of the renal nerves in the pathogenesis of one-kidney renal hypertension in the rat. Hypertension 1981, 3:404–409.
Jing-Yun P, Bishop VS, Ball NA, Haywood JR: Inability of dorsal spinal rhizotomy to prevent wrap hypertension in rats. Hypertension 1985, 7:722–728.
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, 26:861–865.
Klein IHHT, Ligtenberg G, Oey PL, et al.: Sympathetic activity is increased in polycystic kidney disease and is associated with hypertension. J Am Soc Nephrol 2001, 12:2427–2433.
Kopp UC, Olson LA, Dibona GF: Renorenal reflex responses to mechano- and chemoreceptors stimulation in the dog and rat. Am J Physiol 1984, 241:R286-R292.
Calaresu FR, Kim P, Nakamura H, Sato A: Electrophysiological characteristics of renorenal reflexes in the cat. J Physiol 1978, 283:141–154.
Faber JE, Brody MJ: Afferent renal nerve-dependent hypertension following acute renal artery stenosis in the conscious rat. Circ Res 1985, 57:676–688.
Katholi RE, Whitlow PL, Hageman GR, Woods T: Intrarenal adenosine produces hypertension by activating the sympathetic nervous system via the renal nerves. J Hypertens 1984, 2:349–359.
Brody MJ, Johnson AK: Role of the anteroventral third ventricle region in fluid and electrolyte balance, arterial pressure regulation and hypertension. In Frontiers in Neuroendocrinology. Edited by Ganong WF. New York: Raven Press; 1980:249–292.
Ye S, Gumburd M, Campese VM: An acute renal injury may cause a permanent form of neurogenic hypertension. Am J Hypertens 1998, 11:723–728.
Campese VM, Chanana A: Hypertension in dialysis patients. In Principles and Practice of Dialysis. Edited by Henricii WL. Baltimore: Williams & Wilkins; 1999:209–234.
Bredt DS, Hwang PM, Snyder SH: Localization of nitric oxide synthase indicating a neuronal role for nitric oxide. Nature 1990, 347:768–770.
Vincent SR, Kimura H: Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience 1992, 6:755–784.
Tseng CJ, Liu HY, Lin HC, et al.: Cardiovascular effects of nitric oxide in the brain stem nuclei of rats. Hypertension 1996, 27:36–42.
Barinaga M: Is nitric oxide the "retrograde messenger"? Science 1991, 254:1296–1297.
Togashi H, Sakuma I, Yoshioka M, et al.: A central nervous system action of nitric oxide in blood pressure regulation. J Pharmacol Exp Ther 1992, 262:343–347.
Harada S, Tokunaga S, Momohara M, et al.: Inhibition of nitric oxide formation in the nucleus tractus solitarius increases renal sympathetic nerve activity in rabbits. Circ Res 1993, 72:511–516.
Ye S, Nosrati S, Campese VM: Nitric oxide (NO) modulates the neurogenic control of blood pressure in rats with chronic renal failure. J Clin Invest 1997, 99:540–548.
Vaziri ND, Ni Z, Wang XQ, et al.: Downregulation of nitric oxide synthase in chronic renal insufficiency: role of excess PTH. Am J Physiol 1998, 274(4Part 2):F642-F649.
Ichijo T, Katafuchi T, Hori T: Central interleukin-lb enhances splenic sympathetic nerve activity in rats. Brain Res Bull 1994, 34:547–553.
Terao A, Oikawa M, Saito M: Tissue-specific increase in norepinephrine turnover by central interleukin-1, but not by interleukin-6, in rats. Am J Physiol 1994, 266:R400-R404.
Niijima A, Hori T, Aou S, Oomura Y: The effects of interleukinlb on the activity of adrenal splenic and renal sympathetic nerves in the rat. J Autonom Nerv Syst 1991, 36:183–192.
Liu S, Adcock IM, Ols RW, et al.: Lipopolysaccharide treatment in vivo induces widespread tissue expression of inducible nitric oxide synthase mRNA. Biochem Biophys Res Commun 1993, 196:1208–1213.
Robbins RA, Springall DR, Warren JB, et al.: Inducible nitric oxide synthase is increased in murine lung epithelial cells by cytokine stimulation. Biochem Biophys Res Commun 1994, 198:835–843.
Tanazawa T, Suzuki Y, Anzai M, et al.: Vasodilation by intrathecal lipopolysaccharide of the cerebral arteries after subarachnoid haemorrhage in dogs. Acta Neurochir 1996, 138:330–337.
Shibata M, Pazrffnova H, Zucherman SL, et al.: Interleukin-1 beta peptides induce cerebral pial arteriolar dilation in anesthetized newborn pigs. Am J Physiol 1996, 270:R1044-R1050.
Ye S, Mozayeni P, Gamburd M, et al.: Interleukin-1b and neurogenic control of blood pressure in normal rats and rats with chronic renal failure. Am J Physiol 2000, 279:H2786-H2796.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Campese, V.M., Krol, E. Neurogenic factors in renal hypertension. Current Science Inc 4, 256–260 (2002). https://doi.org/10.1007/s11906-002-0016-3
Issue Date:
DOI: https://doi.org/10.1007/s11906-002-0016-3