Hormones and the Pathogenesis of Congestive Heart Failure:Vasopressin, Aldosterone, and Angiotensin II

Abstract

The role of hormones that can influence renal tubular reabsorption of salt and water in congestive heart failure and other states of abnormal fluid retention has been discussed. Available evidence indicates that the antidiuretic hormone of the neurohypophysis plays a nonessential role in the pathogenesis of edema. Oversecretion of aldosterone can be an important, or even an essential, mechanism in the pathogenesis of certain states of edema, such as those of nephrosis and cirrhosis. Advanced congestive heart failure, however, can occur with a normal or only a moderately elevated rate of aldosterone secretion. The observations perhaps suggest that more immediate hemodynamic consequences of heart failure, such as a reduced glomerular filtration rate, also play an important role in causing renal retention of sodium. Increased aldosterone secretion is provoked by an unidentified hemodynamic consequence of cardiac decompensation. When oversecretion occurs, it undoubtedly adds to circulatory embarrassment by promoting more sodium retention. An understanding of the exact role of aldosterone in heart failure awaits clarification of the fundamental problem of the mechanisms involved in the normal control of the secretion of the hormone. Studies of other diseases have yielded helpful clues in this latter regard. The finding of oversecretion of aldosterone in malignant nephrosclerosis led to the demonstration that angiotensin is a potent stimulus to aldosterone secretion and to the suggestion that sodium balance may be regulated by a renal-adrenal (angiotensin-aldosterone) mechanism, which is deranged in malignant hypertension. Recent studies in our laboratory have been designed to determine whether increased amounts of circulating angiotensin could be responsible for the oversecretion of aldosterone of typical secondary aldosteronism. In a model state of secondary aldosteronism (cirrhosis with ascites), it has been found that the pressor responsiveness to infused angiotensin is reduced, a finding that could explain the absence of manifest arterial hypertension even if angiotensin were present in increased amounts in secondary aldosteronism. Angiotensin also failed to increase the rate of aldosterone secretion in cirrhosis with ascites. This might mean that the adrenal cortex is maximally engaged by increased amounts of endogenous trophic hormone (? angiotensin). In further contrast to its effects in normal subjects, in cirrhosis with ascites angiotensin caused a marked natriuresis by modifying the renal tubular reabsorption of sodium. The very potent effects of angiotensin on sodium transport also raised the possibility that an intrarenal action for this substance may be physiologically more important than its effect on aldosterone release. Thus far, crucial experiments are lacking, and other interpretations are possible. It remains to be shown that increased amounts of renin or of angiotensin appear in the circulation of either sodium-depleted normal subjects or patients forming edema. The observations to date suggest, however, that a renal humoral factor (? angiotensin) may be involved in the normal regulation of sodium balance and in the pathogenesis of various states of fluid retention. Furthermore, this renal factor may mediate various stimuli that are known to increase aldosterone secretion to the adrenal cortex. Some critical change in the renal circulation may determine the release of this factor.