Abstract
After 30 years of continuous research into the mechanisms of human hypertension, we summarize the results obtained by the members of the multidisciplinary research group on hypertension of the Clinical Research Institute of Montreal on the disturbances of minerlocorticoid activity in a rigorously selected group of patients with early, mild essential hypertension. We attempt to integrate these findings with those of many other groups working on other aspects of hypertensive cardiovascular diseases. On the assumption that the increased peripheral resistance responsible for hypertension results from an imbalance or a disturbance of the equilibrium between the sympathetic nervous system and norepinephrine on one hand, and the vascular tone, sensitivity and responsiveness of the arterial smooth muscle to norepinephrine and to angiotensin II on the other hand, three models that fit the experimental and clinical facts as known at present are described.
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Selected References
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- BORST J. G., BORST-DE GEUS A. Hypertension explained by Starling's theory of circulatory homoeostasis. Lancet. 1963 Mar 30;1(7283):677–682. doi: 10.1016/s0140-6736(63)91443-0. [DOI] [PubMed] [Google Scholar]
- Beilin L. J., Wade D. N., Honour A. J., Cole T. J. Vascular hyper-reactivity with sodium loading and with desoxycorticosterone induced hypertension in the rat. Clin Sci. 1970 Dec;39(6):793–810. doi: 10.1042/cs0390793. [DOI] [PubMed] [Google Scholar]
- Bhattacharya B. K., Dadkar N. K., Dohadwalla A. N. Vascular reactivity of perfused vascular bed in spontaneously hypertensive and normotensive rats. Br J Pharmacol. 1977 Feb;59(2):243–246. doi: 10.1111/j.1476-5381.1977.tb07485.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bianchi G., Fox U., Di Francesco G. F., Giovanetti A. M., Pagetti D. Blood pressure changes produced by kidney cross-transplantation between spontaneously hypertensive rats and normotensive rats. Clin Sci Mol Med. 1974 Nov;47(5):435–448. doi: 10.1042/cs0470435. [DOI] [PubMed] [Google Scholar]
- Blair-West J. R., Coghlan J. P., Denton D. A., Funder J. W., Nelson J., Scoggins B. A., Wright R. D. Sodium homeostasis, salt appetite, and hypertension. Circ Res. 1970 Oct;27(Suppl):251+–251+. [PubMed] [Google Scholar]
- Bohr D. F., Uchida E. Individualities of vascular smooth muscles in response to angiotensin. Circ Res. 1967 Jul;21(1 Suppl):135+–135+. [PubMed] [Google Scholar]
- Chopde C. T., Brahmankar D. M., Sheorey R. V., Udhoji A. G., Dorle A. K. The effect of acute bilateral adrenalectomy on vasopressor responses to catecholamines in dogs. J Pharm Pharmacol. 1975 Apr;27(4):262–267. doi: 10.1111/j.2042-7158.1975.tb10696.x. [DOI] [PubMed] [Google Scholar]
- Coleman T. G., Manning R. D., Jr, Norman R. A., Jr, Granger H. J., Guyton A. C. The role of salt in experimental and human hypertension. Am J Med Sci. 1972 Aug;264(2):103–110. doi: 10.1097/00000441-197208000-00002. [DOI] [PubMed] [Google Scholar]
- Collins R. D., Weinberger M. H., Dowdy A. J., Nokes G. W., Gonzales C. M., Luetscher J. A. Abnormally sustained aldosterone secretion during salt loading in patients with various forms of benign hypertension; relation to plasma renin activity. J Clin Invest. 1970 Jul;49(7):1415–1426. doi: 10.1172/JCI106359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collis M. G., Alps B. J. The renin-angiotensin system, dietary salt, and increased sensitivity to noradrenaline in mesenteric vasculature preparations from renal/salt hypertensive rats. Cardiovasc Res. 1976 Mar;10(2):232–235. doi: 10.1093/cvr/10.2.232. [DOI] [PubMed] [Google Scholar]
- Collis M. G., Alps B. J. Vascular reactivity to noradrenaline, potassium chloride, and angiotensin II in the rat perfused mesenteric vasculature preparation, during the development of renal hypertension. Cardiovasc Res. 1975 Jan;9(1):118–126. doi: 10.1093/cvr/9.1.118. [DOI] [PubMed] [Google Scholar]
- Cuche J. L., Kuchel O., Barbeau A., Genest J. Urinary homovanillic acid, dopamine and norepinephrine excretion in patients with essential hypertension. Can Med Assoc J. 1975 Feb 22;112(4):443–446. [PMC free article] [PubMed] [Google Scholar]
- DOLE V. P., DAHL L. K., COTZIAS G. C., DZIEWIATKOWSKI D. D., HARRIS C. Dietary treatment of hypertension. II. Sodium depletion as related to the therapeutic effect. J Clin Invest. 1951 Jun;30(6):584–595. doi: 10.1172/JCI102476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dahl L. K., Heine M. Primary role of renal homografts in setting chronic blood pressure levels in rats. Circ Res. 1975 Jun;36(6):692–696. doi: 10.1161/01.res.36.6.692. [DOI] [PubMed] [Google Scholar]
- Dahl L. K. Salt and hypertension. Am J Clin Nutr. 1972 Feb;25(2):231–244. doi: 10.1093/ajcn/25.2.231. [DOI] [PubMed] [Google Scholar]
- Doyle A. E. Vascular reactivity in human hypertension. N Z Med J. 1968 Mar;67(429):295–303. [PubMed] [Google Scholar]
- FLOYER M. A. The effect of nephrectomy and adrenalectomy upon the blood pressure in hypertensive and normotensive rats. Clin Sci. 1951 Nov;10(4):405–421. [PubMed] [Google Scholar]
- FRIEDMAN S. M., NAKASHIMA M., FRIEDMAN C. L. The extrarenal effect of adrenalectomy on sodium and potassium distribution in the rat. Endocrinology. 1958 Mar;62(3):259–267. doi: 10.1210/endo-62-3-259. [DOI] [PubMed] [Google Scholar]
- Fraser R., Brown J. J., Brown W. C., Ferriss J. B., Kennedy A., Lever A. F., Mason P. A., Morton J. J., Nicholls M. G., Ramsay L. E. The adrenal cortex and hypertension: some observations on a possible role for mineralocorticoids other than aldosterone. J Steroid Biochem. 1976 Nov-Dec;7(11-12):963–970. doi: 10.1016/0022-4731(76)90019-4. [DOI] [PubMed] [Google Scholar]
- Freis E. D. Salt, volume and the prevention of hypertension. Circulation. 1976 Apr;53(4):589–595. doi: 10.1161/01.cir.53.4.589. [DOI] [PubMed] [Google Scholar]
- GENEST J., LEMIEUX G., DAVIGNON A., KOIW E., NOWACZYNSKI W., STEYERMARK P. Human arterial hypertension: a state of mild chronic hyperaldosteronism? Science. 1956 Mar 23;123(3195):503–505. doi: 10.1126/science.123.3195.503. [DOI] [PubMed] [Google Scholar]
- GORDON D. B., DRURY D. R., SCHAPIRO S. The salt-fed animal as a test object for pressor substances in the blood of hypertensive animals. Am J Physiol. 1953 Oct;175(1):123–128. doi: 10.1152/ajplegacy.1953.175.1.123. [DOI] [PubMed] [Google Scholar]
- GREISMAN S. E. The reactivity of the capillary bed of the nailfold to circulating epinephrine and nor-epinephrine in patients with normal blood pressure and with essential hypertension. J Clin Invest. 1952 Aug;31(8):782–788. doi: 10.1172/JCI102663. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Genest J., Nowaczynski W. J., Küchel O., Sasaki C. New evidences of disturbances of mineralocorticoid activity in benign, uncomplicated essential hypertension. Trans Am Clin Climatol Assoc. 1972;83:134–146. [PMC free article] [PubMed] [Google Scholar]
- Genest J., Nowaczynski W., Kuchel O., Boucher R., Rojo-Ortega J. M., Constantopoulos G., Ganten D., Messerli F. The adrenal cortex and essential hypertension. Recent Prog Horm Res. 1976;32:377–427. doi: 10.1016/b978-0-12-571132-6.50023-3. [DOI] [PubMed] [Google Scholar]
- Goldberg L. I. Cardiovascular and renal actions of dopamine: potential clinical applications. Pharmacol Rev. 1972 Mar;24(1):1–29. [PubMed] [Google Scholar]
- Haeusler G., Haefely W. Pre- and postjunctional supersensitivity of the mesenteric artery preparation from normotensive and hypertensive rats. Naunyn Schmiedebergs Arch Pharmakol. 1970;266(1):18–33. doi: 10.1007/BF00997779. [DOI] [PubMed] [Google Scholar]
- Hansen T. R., Bohr D. F. Hypertension, transmural pressure, and vascular smooth muscle response in rats. Circ Res. 1975 May;36(5):590–598. doi: 10.1161/01.res.36.5.590. [DOI] [PubMed] [Google Scholar]
- Jones A. W. Altered ion transport in vascular smooth muscle from spontaneously hypertensive rats. Influences of aldosterone, norepinephrine, and angiotensin. Circ Res. 1973 Nov;33(5):563–572. doi: 10.1161/01.res.33.5.563. [DOI] [PubMed] [Google Scholar]
- KAPLAN N. M., SILAH J. G. THE EFFECT OF ANGIOTENSIN II ON THE BLOOD PRESSURE IN HUMANS WITH HYPERTENSIVE DISEASE. J Clin Invest. 1964 Apr;43:659–669. doi: 10.1172/JCI104951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LEE R. E., HOLZE E. A. Peripheral vascular hemodynamics in the bulbar conjunctiva of subjects with hypertensive vascular disease. J Clin Invest. 1951 Jun;30(6):539–546. doi: 10.1172/JCI102470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Larsson C., Weber P., Anggård E. Arachidonic acid increases and indomethacin decreases plasma renin activity in the rabbit. Eur J Pharmacol. 1974 Oct;28(2):391–394. doi: 10.1016/0014-2999(74)90296-9. [DOI] [PubMed] [Google Scholar]
- Lee J. B. Hypertension, natriuresis and the renomedullary prostaglandins: an overview. Prostaglandins. 1973 May;3(5):551–579. doi: 10.1016/0090-6980(73)90095-6. [DOI] [PubMed] [Google Scholar]
- Lewis P. J., Haeusler G. Reduction in sympathetic nervous activity as a mechanism for hypotensive effect of propranolol. Nature. 1975 Jul 31;256(5516):440–440. doi: 10.1038/256440a0. [DOI] [PubMed] [Google Scholar]
- MCGREGOR D. D. THE EFFECT OF SYMPATHETIC NERVE STIMULATION OF VASOCONSTRICTOR RESPONSES IN PERFUSED MESENTERIC BLOOD VESSELS OF THE RAT. J Physiol. 1965 Mar;177:21–30. doi: 10.1113/jphysiol.1965.sp007572. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MCQUEEN E. G. Vascular reactivity in experimental renal and renoprival hypertension. Clin Sci. 1956 Nov;15(4):523–532. [PubMed] [Google Scholar]
- Manku M. S., Mtabaji J. P., Horrobin D. F. Effects of prostaglandins on baseline pressure and responses to noradrenaline in a perfused rat mesenteric artery preparation. PGE1 as an antagonist of PGE2. Prostaglandins. 1977 Apr;13(4):701–709. doi: 10.1016/0090-6980(77)90242-8. [DOI] [PubMed] [Google Scholar]
- Margolius H. S., Horwitz D., Pisano J. J., Keiser H. R. Urinary kallikrein excretion in hypertensive man. Relationships to sodium intake and sodium-retaining steroids. Circ Res. 1974 Dec;35(6):820–825. doi: 10.1161/01.res.35.6.820. [DOI] [PubMed] [Google Scholar]
- McGregor D. D., Smirk F. H. Vascular responses in mesenteric arteries from genetic and renal hypertensive rats. Am J Physiol. 1968 Jun;214(6):1429–1433. doi: 10.1152/ajplegacy.1968.214.6.1429. [DOI] [PubMed] [Google Scholar]
- Mendlowitz M. Vascular reactivity in essential and renal hypertension in man. Am Heart J. 1967 Jan;73(1):121–128. doi: 10.1016/0002-8703(67)90317-1. [DOI] [PubMed] [Google Scholar]
- Messerli F. H., Genest J., Nowaczynski W., Kuchel O., Honda M., Latour Y., Dumont G. Splanchnic blood flow in essential hypertension and in hypertensive patients with renal artery stenosis. Circulation. 1975 Jun;51(6):1114–1119. doi: 10.1161/01.cir.51.6.1114. [DOI] [PubMed] [Google Scholar]
- Myers M. G., Lewis P. J., Reid J. L., Dollery C. T. Brain concentration of propranolol in relation to hypotensive effect in the rabbit with observations on brain propranolol levels in man. J Pharmacol Exp Ther. 1975 Feb;192(2):327–335. [PubMed] [Google Scholar]
- Nowaczynski W., Kuchel O., Genest J. A decreased metabolic clearance rate of aldosterone in benign essential hypertension. J Clin Invest. 1971 Oct;50(10):2184–2190. doi: 10.1172/JCI106713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- RAAB W., HUMPHREYS R. J., MAKOUS N., DeGRANDPRE R., GIGEE W. Pressor effects of epinephrine, norepinephrine and desoxycorticosterone acetate weakened by sodium withdrawal. Circulation. 1952 Sep;6(3):373–377. doi: 10.1161/01.cir.6.3.373. [DOI] [PubMed] [Google Scholar]
- RAAB W. The integrated role of catecholamines, mineralocorticoids and sodium in hyper- and hypotension; a working hypothesis. J Mt Sinai Hosp N Y. 1952 May-Jun;19(1):233–239. [PubMed] [Google Scholar]
- RAMEY E. R., GOLDSTEIN M. S., LEVINE R. Action of nor-epinephrine and adrenal cortical steroids on blood pressure and work performance of adrenalectomized dogs. Am J Physiol. 1951 May;165(2):450–455. doi: 10.1152/ajplegacy.1951.165.2.450. [DOI] [PubMed] [Google Scholar]
- Richardson K. S., Nowaczynski W., Genest J. Letter: Aldosterone-binding proteins in human plasma. N Engl J Med. 1976 Jul 8;295(2):114–114. doi: 10.1056/NEJM197607082950228. [DOI] [PubMed] [Google Scholar]
- Somlyo A. P., Somlyo A. V. Vascular smooth muscle. II. Pharmacology of normal and hypotensive vessels. Pharmacol Rev. 1970 Jun;22(2):249–353. [PubMed] [Google Scholar]
- Tobian L., Jr A viewpoint concerning the enigma of hypertension. Am J Med. 1972 May;52(5):595–609. doi: 10.1016/0002-9343(72)90051-4. [DOI] [PubMed] [Google Scholar]
- Tobian L., O'Donnell M. Renal prostaglandins in relation to sodium regulation and hypertension. Fed Proc. 1976 Oct;35(12):2388–2392. [PubMed] [Google Scholar]
- Villamil M. F., Nachev P., Kleeman C. R. Effect of prolonged infusion of angiotensin II on ionic composition of the arterial wall. Am J Physiol. 1970 May;218(5):1281–1286. doi: 10.1152/ajplegacy.1970.218.5.1281. [DOI] [PubMed] [Google Scholar]
- WINER B. M. The antihypertensive actions of benzothiadiazines. Circulation. 1961 Feb;23:211–218. doi: 10.1161/01.cir.23.2.211. [DOI] [PubMed] [Google Scholar]
- Weinsier R. L. Salt and the development of essential hypertension. Prev Med. 1976 Mar;5(1):7–14. doi: 10.1016/0091-7435(76)90003-7. [DOI] [PubMed] [Google Scholar]
- Williams G. H., Rose L. I., Dluhy R. G., McCaughn D., Jagger P. I., Hickler R. B., Lauler D. P. Abnormal responsiveness of the renin aldosterone system to acute stimulation in patients with essential hypertension. Ann Intern Med. 1970 Mar;72(3):317–326. doi: 10.7326/0003-4819-72-3-317. [DOI] [PubMed] [Google Scholar]
- ZWEIFACH B. W., SHORR E., BLACK M. M. The influence of the adrenal cortex on behavior of terminal vascular bed. Ann N Y Acad Sci. 1953 Jul 17;56(4):626–633. doi: 10.1111/j.1749-6632.1953.tb27383.x. [DOI] [PubMed] [Google Scholar]
- Zusman R. M., Spector D., Caldwell B. V., Speroff L., Schneider G., Mulbow P. J. The effect of chronic sodium loading and sodium restriction on plasma prostaglandin A, E, and F concentrations in normal humans. J Clin Invest. 1973 May;52(5):1093–1098. doi: 10.1172/JCI107274. [DOI] [PMC free article] [PubMed] [Google Scholar]
