Endocrine Mechanisms in Congestive Cardiac Failure

Summary

Overactivity of the renin-angiotensin-aldosterone system occurs in the syndrome of congestive cardiac failure. Aldosterone overactivity is crucially involved in maintaining the oedematous state as evidenced by its often complete correction by adrenalectomy, or by aldosterone antagonists, in both experimental and clinical heart failure.

The hyperaldosteronism of heart failure can also be attacked by angiotensin-converting enzyme (ACE) inhibition, which not only blocks the angiotensin drive to aldosterone, but also unloads the heart by blocking renin-angiotensin-mediated vasoconstriction. Accordingly, ACE inhibition alone, if continued in full dosage, can often reduce or obviate the need for daily thiazide diuretic therapy. This specific, two-pronged therapy with fewer side effects emerges as a primary strategy for the treatment of congestive heart failure.

To learn more about why and how the renin system becomes involved in heart failure, the renal functional abnormalities have been re-examined. The effects of sodium administration on central haemodynamics and on the activity of the renin system have also been studied. This research has led to a consideration of the role of atrial natriuretic hormone in this pathophysiological interplay.

The study recharacterised renal haemodynamic patterns and indicated that in congestive heart failure there is a disproportionate diversion of blood away from the kidneys because of afferent vasoconstriction. However, the glomerular filtration rate is maintained by concurrent efferent arteriolar constriction, expressed by a rising filtration fraction. As heart failure advances, the filtration fraction can no longer rise. At this point, the glomerular filtration rate becomes flow-dependent and falls commensurately with the declining cardiac output. These intrarenal patterns may be mediated in part by increased intrarenal renin activity resulting from heart failure and diuretic therapy.

A further study of the abnormal renin system activity operating in heart failure has shown it to be very sensitive to dietary salt intake. Thus, consuming modest amounts of salt (100 mEq/day) was sufficient to markedly suppress renin and aldosterone values. However, since peripheral resistance was not changed, another non-renin, sodium-related mechanism must take over to sustain increased arterial constriction. The fact that captopril challenge evoked no response before and a large response after sodium depletion supports this concept.

Preliminary data suggest that atrial natriuretic hormone may also be important in congestive heart failure by opposing renin system activity at 4 sites. More research to define often crucial endocrine and renal abnormalities of heart failure could provide even more specific therapies.