Interrelationships Between Angiotensin, Norepinephrine, Epinephrine, Aldosterone Secretion, and Electrolyte Metabolism in Man

Abstract

Oversecretion of aldosterone is a consistent finding in the syndrome of malignant hypertension. Infusion of angiotensin has been consistently shown to induce an increased secretion of aldosterone by the adrenal cortex in normal human subjects. Because renal damage is so prominent in malignant hypertension, it seems possible that renin release and then aldosterone oversecretion by the adrenal cortex are involved in the pathogenesis of this disorder. These findings support the possibility that there is a renal-adrenal system which operates for the normal regulation of electrolyte balance. This system might function to maintain and protect renal perfusion by promoting sodium retention via stimulation of the adrenal cortex. Our recent work has been predicated on the possibility that aldosterone secretion is chiefly regulated by 1 specific trophic hormone (possibly angiotensin), oversecretion of which accounts for the increased secretion of aldosterone observed in various other conditions. Preliminary studies designed to investigate the possible role of angiotensin in the marked oversecretion of aldosterone found in cirrhosis have been reported. It has been observed that patients with cirrhosis and ascites may be less sensitive to both angiotensin and norepinephrine so that more drug is required to produce a given pressor response. Further-more, aldosterone secretion could not be augmented by administering angiotensin in these patients. While several interpretations are possible, these findings are consistent with the view that the adrenal cortex is already maximally stimulated by circulating endogenous angiotensin. Because of reduced pressor responsiveness, increased amounts of angiotensin could circulate without causing hypertension. This hypothesis awaits actual demonstration of increased amounts of circulating renin or angiotensin in this condition (and others) associated with aldosteronism. Proper study of the interrelationships between pressor substances, aldosterone secretion, and sodium balance requires that effects of the different types of pressor agents be compared under similar circumstances. Thus, both norepinephrine and angiotensin affect the renal excretion of electrolytes. Both can cause a natriuresis in normal or hypertensive subjects. In normal subjects, the natriuresis occurs inconsistently but seems more readily induced after sodium depletion. Angiotensin has been found to produce a marked increase in sodium excretion in patients with cirrhosis and ascites who have increased aldosterone secretion. In equipressor doses, the natriuresis of angiotensin is of strikingly greater magnitude than that of norepinephrine, possibly indicating that the peptide affects tubular transport of sodium. The natriuresis effected by these pressor agents seems independent of their effect on aldosterone secretion because medullary hormones often suppress aldosterone output, whereas angiotensin increases it. Further study is necessary to define more specifically the conditions which determine these responses and interrelationships. The results to date support the view that an aldosterone-regulating hormone (possibly angiotensin) could be elaborated as a result of a critical change in intrarenal pressure.