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The sympathetic nervous system in hypertension due to unilateral renal artery stenosis in man

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Abstract

The contribution of neurogenic mechanisms in maintaining hypertension was investigated in 13 patients with unilateral renal artery stenosis (twelve with normal, one with grossly elevated plasma renin levels) by determining the haemodynamic and hormonal responses to the centrally acting sympatholytic agent, clonidine. The same patients were studied after captopril to determine the dependency of their blood pressure on the direct peripheral effects of angiotensin-II. Sixteen patients with essential hypertension (normal plasma renin) were additionally studied after clonidine. After clonidine, blood pressure fell markedly in patients with renal artery stenosis (17 ± 3%) and essential hypertension (18 ± 2%). In both groups, clonidine lowered cardiac output by a reduction in stroke volume and heart rate; forearm vascular resistance was unchanged but digital skin vascular resistance fell. Plasma noradrenaline levels were normal in both groups and fell after clonidine; plasma renin activity and aldosterone levels were unchanged. After captopril, blood pressure fell minimally (5 ± 3%) in renal artery stenosis patients; cardiac output fell and forearm and digital skin vascular resistance were unchanged. Plasma renin activity rose, plasma aldosterone fell and plasma noradrenaline was unchanged after captopril. In the patient with grossly elevated renin levels, blood pressure fell minimally (6%) after clonidine, but unlike others fell profoundly (37%) after captopril. We conclude that, in the majority of our renal artery stenosis patients, despite the elevated blood pressure, sympathetic nervous activity was not reduced. Central neurogenic mechanisms appear to play an important role in maintaining raised blood pressure. In the same patients the peripheral effects of angiotensin-II did not maintain vascular tone or hypertension. The ischaemic kidney has a key role however, as revascularization or nephrectomy cured or ameliorated the hypertension.

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References

  1. Brown JJ, Cuesta V, Davies DL, Lever AF, Morton JJ, Padfield PL, Robertson JIS, Trust P, Bianchi G, Schalekamp MAD. Mechanism of renal hypertension.Lancet 1976;i: 1219–1221.

    Google Scholar 

  2. Bianchi G, Baldoli E, Lecca R, Barbin P. Pathogenesis of arterial hypertension after the constriction of renal artery leaving the opposite kidney intact both in anaesthetised and in the conscious dog.Clin Sci 1972;42: 651–664.

    PubMed  Google Scholar 

  3. Reigger AJF, Lever AF, Millar JA, Morton JG, Slack B. Correction of renal hypertension in the rat by prolonged infusion of angiotensin.Lancet 1977;ii: 1317–1319.

    Google Scholar 

  4. Brody MJ, Barron KW, Berecek KH, Faber JE, Lappe RW. Neurogenic mechanisms of experimental hypertension. In: Genest J, Kuchel O, Hamet P, Cantin M, eds.Hypertension Physiopathology and Treatment. New York: McGraw Hill Inc, 1983; 117–140.

    Google Scholar 

  5. Katholi RE, Whitlow PL, Winternitz SR, Oparil S. Importance of renal nerves in established two kidney one clip Goldblatt hypertension.Hypertension 1982;4 (suppl II): 166–174.

    PubMed  Google Scholar 

  6. Appel PL, Kram HB, Mackabee J, Fleming AW, Shoemaker WC. Comparison of measurement of cardiac output by bioimpedence and thermodilution in severely ill surgical patients.Crit Care Med 1986;14: 933–935.

    PubMed  Google Scholar 

  7. Whitney RJ. The measurement of volume changes in human limbs.J Physiol (Lond) 1953;121: 1–27.

    Google Scholar 

  8. Nilsson GE, Tenland T, Oberg PA. A new instrument for continuous measurement of tissue blood flow by light beating spectroscopy.IEEE Trans Biomed Engg 1980;27: 1–8.

    Google Scholar 

  9. Tooke JE, Ostergen J, Fagrell B. Synchronous assessment of human skin microcirculation by laser Doppler flowmetry and dynamic capillaroscopy.Int J Microcirc Clin Exp 1983;2: 277–284.

    PubMed  Google Scholar 

  10. Boyd GW, Adamson AR, Fitz AE, Peart WS. Radioimmunoassay determination of plasma renin activity.Lancet 1969;i: 213–218.

    Google Scholar 

  11. Few JD, Chaudry S, James VHT. The direct determination of aldosterone in human saliva.J Steroid Biochem 1984;21: 87–92.

    PubMed  Google Scholar 

  12. Smeddes F, Kraak JC, Poppe H. A simple and fast solvent extraction system for selective and quantitative isolation of adrenaline noradrenaline and dopamine from plasma and urine.J Chromat 1982;231: 25–39.

    Google Scholar 

  13. Dargie HJ. Franklin SS, Reid JL. Central and peripheral noradrenaline in the two kidney model of renovascular hypertension in the rat.Br J Pharmac 1977;61: 213–215.

    Google Scholar 

  14. Swartz SL, Williams GH, Hollenberg NK, Moore TJ, Dluhy RG. Converting enzyme inhibition in essential hypertension: the hypotensive response does not reflect only reduced angiotensin-II formation.Hypertension 1979;i: 106–111.

    Google Scholar 

  15. Zusman RM. Renin and non-renin-mediated antihypertensive actions of converting enzyme inhibitors.Kidney Int 1984;25: 969–983.

    PubMed  Google Scholar 

  16. Hatton R, Clough DP. Captopril interferes with neurogenic vasoconstriction in the pithed rat by angiotensin-dependent mechanisms.J Cardiovasc Pharm 1982;4: 116–123.

    Google Scholar 

  17. Kobinger W, Walland A. Investigations into the mechanism of the hypotensive effect of 2-(26-dichlorophenylamino)-2-imidazoline-HCI.Eur J Pharmacol 1967;2: 155–162.

    PubMed  Google Scholar 

  18. Schmitt H, Schmitt H, Boissier JR, Giudicelli JF. Centrally mediated decrease in sympathetic tone induced by 2-(26-dichlorophenyl-amino)-2-imidazoline hydrochloride (St. 155 Catapressan).Eur J Pharmacol 1967;2: 147–148.

    PubMed  Google Scholar 

  19. Reid JL, Wing LMH, Mathias CJ, Frankel HL, Neill E. The central hypotensive effect of clonidine: studies in tetraplegic subjects.Clin Pharm Ther 1977;21: 375–381.

    Google Scholar 

  20. Mathias CJ, Reid JL, Wing LMH, Frankel HL, Christensen NJ. Antihypertensive effects of clonidine in tetraplegic subjects devoid of central sympathetic control.Clin Sci Mol Med 1979;57: 425–428s.

    Google Scholar 

  21. Kooner JS, Edge W, Frankel HL, Peart WS, Mathias CJ. Haemodynamic actions of clonidine in tetraplegia—effects at rest and during bladder stimulation.Paraplegia 1988;26: 200–203.

    PubMed  Google Scholar 

  22. Robertson D, Goldberg MR, Tung CS, Hollister AS, Robertson RM. Use of alpha2 adrenoceptor agonists and antagonists in the functional assessment of the sympathetic nervous system.J Clin Invest 1986;78: 576–581.

    PubMed  Google Scholar 

  23. Baum T, Shropshire AT. Susceptibility of spontaneous sympathetic nervous outflow and sympathetic reflexes to depression by clonidine.Eur J Pharmacol 1977;44: 121–129.

    PubMed  Google Scholar 

  24. Starke K, Altmann KP. Inhibition of adrenergic neurotransmission by clonidine: an action of prejunctional alpha-adrenoceptors.Neuropharmacology 1973;2: 339–347.

    Google Scholar 

  25. Haeusler G. Studies on the possible contribution of peripheral presynaptic action of clonidine and dopamine to their vascular effects underin vivo conditions.Naunyn-Schmiedeberg's Arch Pharmacol 1976;295: 191–202.

    Google Scholar 

  26. Zaimis E, Hannington E. A possible pharmacological approach to migraine.Lancet 1969;iii: 298–300.

    Google Scholar 

  27. Mendelsohn FAO, Quirion R, Saavedra JM, Aguilera G, Catt KJ. Autoradiographic localization of angiotensin-II receptors in rat brain.Proc Natl Acad Sci 1984;81: 1575–1579.

    PubMed  Google Scholar 

  28. Haywood JR, Fink GD, Buggy J, Boutelle S, Johnson AK, Brody MJ. Prevention of two-kidney one-clip renal hypertension in rat by ablation of AV3V tissue.Am J Physiol 1983;245: H683-H689.

    PubMed  Google Scholar 

  29. Nayler WG, Price JM, Swann JB, McInnes I, Race D, Lowe TE. Effect of the hypotensive drug St 155 (Catapress) on the heart and peripheral circulation.J Pharmacol Exp Ther 1968;164: 45–59.

    PubMed  Google Scholar 

  30. Nayler WG, Price JM, Stone J. Further observations on the cardiovascular effects of St-155 (Catapress).J Pharmacol Exp Ther 1969;166: 364.

    PubMed  Google Scholar 

  31. Ehringer H. Effect of 2-(26-dichlorophenylamino)-2-imidazoline hydrochloride on extremity blood flow blood pressure and venous capacity in normotensive individuals.Arzneimittel-Forsch 1966;16: 1165–1169.

    Google Scholar 

  32. Muir AL, Burton JL, Lawrie DM. Circulatory effects at rest and exercise of clonidine an imidasoline derivative with hypotensive properties.Lancet 1969;ii: 181–185.

    Google Scholar 

  33. Grant RT, Bland EF. Observations on the arteriovenous anastomosis in the human skin and the birds foot with special reference to the reaction to cold.Heart 1931;15: 385–407.

    Google Scholar 

  34. Roddie IC. Circulation to the skin and adipose tissue. In:Handbook of Physiology: the cardiovascular system. Vol III. Bethesda, MD: American Physiological Society, 1983; 285–317.

    Google Scholar 

  35. Kooner JS, Stone F, Birch R, Frankel HL, Peart WS, Mathias CL. Vascular effects of clonidine in patients with tetraplegia and unilateral brachial plexus injury.Clin Exp Hypert 1988;A10 (suppl 1): 405–412.

    Google Scholar 

  36. Blair DA, Glover WE, Roddie IC. Cutaneous vasomotor nerves to the head and trunk.J Appl Physiol 1961;16: 119–122.

    Google Scholar 

  37. Goldstein DS, McCarty R, Polinsky RJ, Kopin IJ. Relationship between plasma noradrenaline and sympathetic neural activity.Hypertension 1983;5: 552–559.

    PubMed  Google Scholar 

  38. Brown MJ, Jenner DA, Allison DJ, Dollery CT. Variations in the individual organ release of noradrenaline measured by an improved radioenzymatic technique; limitation of peripheral venous measurements in the assessment of sympathetic nervous activity.Clin Sci 1981;61: 585–590.

    PubMed  Google Scholar 

  39. Mancia G, Grassi G.Clinical Autonomic Research. 1991;1: 245–249.

    PubMed  Google Scholar 

  40. Reid JL, Mathias CJ, Jones DH, Wing LMH. The contribution of central and peripheral adrenoceptors to the actions of clonidine and alpha methyldopa in man. In: Fuxe K, Goldstein M, Hokfelt B, Hokfelt T, eds.Central Adrenaline Neurons. Oxford: Pergamon Press, 1979; 317–325.

    Google Scholar 

  41. Julius S, Esler M.The Nervous System in Hypertension. Springfield, IL: Charles C Thomas, 1976.

    Google Scholar 

  42. Philipp T, Distler A, Cordes U. Sympathetic nervous system and blood pressure control in essential hypertension.Lancet 1978;ii: 959–963.

    Google Scholar 

  43. Kuchel O. The autonomic nervous system and blood pressure regulation in human hypertension. In: Genest J, Kuchel O, Hamet P, Cantin M, eds.Hypertension Physiopathology and Treatment. New York: McGraw Hill Inc, 1983; 140–160.

    Google Scholar 

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Authors and Affiliations

  1. Cardiovascular Medicine Unit, Department of Medicine, St Mary's Hospital Medical Schooll/Imperial College, London, UK

    Jaspal S. Kooner MD (MRCP), W. Stanley Peart MD (FRCP, FRS) & Christopher J. Mathias DPhil (FRCP)

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  1. Jaspal S. Kooner MD
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  2. W. Stanley Peart MD
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  3. Christopher J. Mathias DPhil
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Kooner, J.S., Peart, W.S. & Mathias, C.J. The sympathetic nervous system in hypertension due to unilateral renal artery stenosis in man. Clinical Autonomic Research 1, 195–204 (1991). https://doi.org/10.1007/BF01824987

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  • DOI: https://doi.org/10.1007/BF01824987

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