Current Hypertension Reports

, Volume 2, Issue 3, pp 319–326 | Cite as

Role of the sympathetic nervous system in human renovascular hypertension

  • Mats Johansson
  • Peter Friberg


The findings in humans as to whether elevated sympathetic nerve activity contributes to renovascular hypertension have been less consistent compared with the results obtained in experimental models of renovascular hypertension. Collectively, there are several lines of evidence to support the view that sympathetic nerve activity is elevated in patients with renovascular hypertension. It is uncertain, however, whether this adrenergic overactivity is specific for renovascular hypertension per se, or the cause of severe hypertension with target organ damage. Central or peripheral stimulation of sympathetic nerve activity by angiotensin II, or stimulation of central sympathetic outflow via afferent renal nerves of ischemic kidneys, are possible mechanisms to explain the elevated sympathetic nerve activity in renovascular hypertension. Therapy that diminishes the activity of the sympathetic nervous system and the renin-angiotensin system seems rational and could perhaps also improve the poor prognosis for these patients.


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References and Recommended Reading

  1. 1.
    Dalakos TG, Streeten DH, Jones D, Obeid A: "Malignant" hypertension resulting from atheromatous embolization predominantly of one kidney. Am J Med 1974, 57:135–138.PubMedCrossRefGoogle Scholar
  2. 2.
    Johansson M, Herlitz H, Jensen G, et al.: Increased cardiovascular mortality in hypertensive patiens with renal artery stenosis. Relation to sympathetic activation, renal function and treatment regimens. J Hypertens 1999, 17:1743–1750. A study showing elevated cardiovascular mortality in patients with hypertension and renovascular disease compared with the normal population of Sweden. Elevated plasma NE concentrations did not predict an adverse prognosis and mortality remained high whether revascularization was performed or not, possibly due to concomitant coronary disease.PubMedCrossRefGoogle Scholar
  3. 3.
    Preston RA, Epstein M: Ischemic renal disease: an emerging cause of chronic renal failure and end-stage renal disease [editorial]. J Hypertens 1997, 15:1365–1377.PubMedCrossRefGoogle Scholar
  4. 4.
    Brown JJ, Davies DL, Morton JJ, et al.: Mechanism of renal hypertension. Lancet 1976, 1:1219–1221.PubMedCrossRefGoogle Scholar
  5. 5.
    Folkow B, Di-Bona GF, Hjemdahl P, et al.: Measurements of plasma norepinephrine concentrations in human primary hypertension. A word of caution on their applicability for assessing neurogenic contributions. Hypertension 1983, 5:399–403.PubMedGoogle Scholar
  6. 6.
    DiBona GF, Kopp UC: Neural control of renal function. Physiol Rev 1997, 77:75–197.PubMedGoogle Scholar
  7. 7.
    Ferguson DW, Hayes DW: Nifedipine potentiates cardiopulmonary baroreflex control of sympathetic nerve activity in healthy humans. Direct evidence from microneurographic studies. Circulation 1989, 80:285–298.PubMedGoogle Scholar
  8. 8.
    Goldblatt H, Lynch J, Hanzal R, Summerville W: The production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med 1934, 59:347–378.CrossRefPubMedGoogle Scholar
  9. 9.
    Miller ED Jr, Samuels AI, Haber E, Barger AC: Inhibition of angiotensin conversion and prevention of renal hypertension. Am J Physiol 1975, 228:448–453.PubMedGoogle Scholar
  10. 10.
    Brunner HR, Kirshman JD, Sealey JE, Laragh JH: Hypertension of renal origin: evidence for two different mechanisms. Science 1971, 174:1344–1346.PubMedCrossRefGoogle Scholar
  11. 11.
    Sigmon DH, Beierwaltes WH: Influence of nitric oxide in the chronic phase of two-kidney, one clip renovascular hypertension. Hypertension 1998, 31:649–656. In the chronic phase 2K-1C model of renovascular hypertension there was only a moderate reduction of blood pressure after losartan, indicating a prevailing angiotensin-independent vasoconstriction. The authors conclude that in the early and chronic phases of 2K-1C hypertension, nitric oxide contributes significantly to buffer the hypertension and maintain perfusion of both kidneys by counterbalancing vasoconstriction.PubMedGoogle Scholar
  12. 12.
    Nakada T, Kubota Y, Suzuki H, et al.: Suppression of sympathetic nervous system attenuates the development of twokidney, one-clip Goldblatt hypertension. J Urol 1996, 156:1480–1484.PubMedCrossRefGoogle Scholar
  13. 13.
    Suzuki H, Ferrario CM, Speth RC, et al.: Alterations in plasma and cerebrospinal fluid norepinephrine and angiotensin II during the development of renal hypertension in conscious dogs. Hypertension 1983, 5:I139-I148.PubMedGoogle Scholar
  14. 14.
    Antonaccio MJ, Ferrone RA, Waugh M, et al.: Sympathoadrenal and renin-angiotensin systems in the development of two-kidney, one clip renal hypertension in rats. Hypertension 1980, 2:723–781.PubMedGoogle Scholar
  15. 15.
    Bunag R, Eferakeya A: Immediate hypotensive after-effects of posterior hypothalamic lesions in awake rats with spontaneous, renal, or Doca hypertension. Cardiovasc Res 1976, 10:663–671.PubMedGoogle Scholar
  16. 16.
    Peach MJ, Bumpus FM, Khairallah PA: Inhibition of norepinephrine uptake in hearts by angiotensin II and analogs. J Pharmacol Exp Ther 1969, 167:291–299.PubMedGoogle Scholar
  17. 17.
    Brody MJ, Varner KJ, Vasquez EC, Lewis SJ: Central nervous system and the pathogenesis of hypertension. Sites and mechanisms. Hypertension 1991, 18:III7-III12.PubMedGoogle Scholar
  18. 18.
    Majewski H, Hedler L, Schurr C, Starke K: Modulation of noradrenaline release in the pithed rabbit: a role for angiotensin II. J Cardiovasc Pharmacol 1984, 6:888–896.PubMedCrossRefGoogle Scholar
  19. 19.
    Farr WC, Grupp G: Ganglionic stimulation: mechanism of the positive inotropic and chronotropic effects of angiotensin. J Pharmacol Exp Ther 1971, 177:48–55.PubMedGoogle Scholar
  20. 20.
    Katholi RE, Whitlow PL, Hageman GR, Woods WT: Intrarenal adenosine produces hypertension by activating the sympathetic nervous system via the renal nerves in the dog. J Hypertens 1984, 2:349–359.PubMedGoogle Scholar
  21. 21.
    Wyss JM, Aboukarsh N, Oparil S: Sensory denervation of the kidney attenuates renovascular hypertension in the rat. Am J Physiol 1986, 250:H82-H86.PubMedGoogle Scholar
  22. 22.
    Folkow B: "Structural factor" in primary and secondary hypertension. Hypertension 1990, 16:89–101.PubMedGoogle Scholar
  23. 23.
    Choudhri AH, Cleland JG, Rowlands PC, et al.: Unsuspected renal artery stenosis in peripheral vascular disease [see comments]. BMJ 1990, 301:1197–1198.PubMedGoogle Scholar
  24. 24.
    Esler M, Jennings G, Lambert G, et al.: Overflow of catecholamine neurotransmittor to the circulation: source, fate and functions. Physiol Rev 1990, 70:963–985.PubMedGoogle Scholar
  25. 25.
    Esler M, Jackman G, Bobik A, et al.: Determination of norepinephrine apparent release rate and clearance in humans. Life Sci 1979, 25:1461–1470.PubMedCrossRefGoogle Scholar
  26. 26.
    Bradley T, Hjemdahl P: Further studies on renal nerve stimulation induced release of noradrenaline and dopamin from the canine kidney in situ. Acta Physiol Scand 1984, 122:367–379.Google Scholar
  27. 27.
    Noshiro T, Saigusa T, Way D, et al.: Norepinephrine spillover faithfully reflects renal sympathetic nerve activity in conscious rabbits. Am J Physiol 1991, 261:F44-F50.PubMedGoogle Scholar
  28. 28.
    Kopin IJ, Rundqvist B, Friberg P, et al.: Different relationships of spillover to release of norepinephrine in human heart, kidneys, and forearm [published erratum appears in Am J Physiol 1998, 275:R667]. Am J Physiol 1998, 275:R165-R173.PubMedGoogle Scholar
  29. 29.
    Vallbo Å, Hagbarth K-E, Torebjörk H, Wallin B: Somatosensory, proprioceptive and sympathetic activity in human peripheral nerves. Physiol Rev 1979, 59:919–957.PubMedGoogle Scholar
  30. 30.
    Wallin B, Elam M: Insights in intraneural recordings of sympathetic nerve traffic in humans. News Physiol Sci 1994, 9:7–11.Google Scholar
  31. 31.
    Gordon RD, Bachmann AW, Jackson RV, Saar N: Increased sympathetic activity in renovascular hypertension in man. Clin Exp Pharmacol Physiol 1982, 9:277–281.PubMedGoogle Scholar
  32. 32.
    Kooner JS, Peart WS, Mathias CJ: The sympathetic nervous system in hypertension due to unilateral renal artery stenosis in man. Clin Auton Res 1991, 1:195–204.PubMedCrossRefGoogle Scholar
  33. 33.
    Miyajima E, Yamada Y, Yoshida Y, et al.: Muscle sympathetic nerve activity in renovascular hypertension and primary aldosteronism. Hypertension 1991, 17:1057–1062.PubMedGoogle Scholar
  34. 34.
    Grassi G, Cattaneo BM, Seravalle G, et al.: Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension 1998, 31:68–72. The authors reported reduced MSA in secondary compared with primary hypertension. Interpretation of the data is limited by the study design where patients with pheochromocytoma and patients with renal artery stenosis were lumped together in the group of secondary hypertensives.PubMedGoogle Scholar
  35. 35.
    Johansson M, Elam M, Rundqvist B, et al.: Increased sympathetic nerve activity in renovascular hypertension. Circulation 1999, 99:2537–2542. This study provides evidence for elevated sympathetic nerve activity in patients with renal artery stenosis and hypertension. Sympathetic nerve activity was assessed by both radiotracer technique and microneurography. The diagnosis of renovascular hypertension was proven by cure or improvement of hypertension after revascularization in a subgroup of patients.PubMedGoogle Scholar
  36. 36.
    Rundqvist B, Elam M, Bergmann-Sverrisdottir Y, et al.: Increased cardiac adrenegic drive precedes generalized sympathetic activation in human heart failure. Circulation 1997, 95:169–175.PubMedGoogle Scholar
  37. 37.
    Matsukawa T, Mano T, Gotoh E, Ishii M: Elevated sympathetic nerve activity in patients with accelerated essential hypertension. J Clin Invest 1993, 92:25–28.PubMedGoogle Scholar
  38. 38.
    Converse R Jr, Jacobsen TN, Toto RD, et al.: Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 1992, 327:1912–1918.PubMedCrossRefGoogle Scholar
  39. 39.
    Mörlin C, Fagius J, Hägg A, et al.: Continous recording of muscle nerve sympathetic activity during percutaneous transluminal angioplasty in renovascular hypertension in man. J Hypertens 1990, 8:239–244.PubMedCrossRefGoogle Scholar
  40. 40.
    Ligtenberg G, Blankestijn PJ, Oey PL, et al.: Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure [see comments]. N Engl J Med 1999, 340:1321–1328. This study showed elevated MSA in patients with moderately reduced renal function compared with healthy controls. Using a cross-over design, the authors showed reduced MSA after chronic treatment with an ACE inhibitor, whereas amlodipine, a calcium channel blocker, increased MSA.PubMedCrossRefGoogle Scholar
  41. 41.
    Aars H, Akre S: Effect of angiotensin on sympathetic nerve activity. Acta Physiol Scand 1968, 74:134–141.PubMedCrossRefGoogle Scholar
  42. 42.
    McGiff JC, Fasy TM: The relationship of the renal vascular activity of angiotensin II to the autonomic nervous system. J Clin Invest 1965, 44:1911–1923.PubMedCrossRefGoogle Scholar
  43. 43.
    Conlon P, Athirakul K, Kovalik E, et al.: Survival in renovascular disease. J Am Soc Nephrol 1998, 9:252–256.PubMedGoogle Scholar
  44. 44.
    Yusuf S, Sleight P, Pogue J, et al.: Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators [see comments]. N Engl J Med 2000, 342:145–153. Important study showing reduced rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who did not have known low left ventricular ejection fraction or heart failure. The results are relevant to patients with renovascular hypertension who present similar clinical characteristics as the population of the HOPE study.PubMedCrossRefGoogle Scholar
  45. 45.
    Kaye DM, Lefkovits J, Jennings GL, et al.: Adverse consequences of high sympathetic nervous activity in the failing human heart. J Am Coll Cardiol 1995, 26:1257–1263.PubMedCrossRefGoogle Scholar
  46. 46.
    Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF) [see comments]. Lancet 1999, 353:2001–2007.Google Scholar

Copyright information

© Current Science Inc 2000

Authors and Affiliations

  • Mats Johansson
    • 1
  • Peter Friberg
    • 1
  1. 1.Department of Clinical PhysiologyGöteborg University, Sahlgrenska University HospitalGöteborgSweden

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