Adaptive and maladaptive actions of angiotensin II in patients with severe congestive heart failure.

The renin-angiotensin system appears to have evolved millions of years ago as a primary attempt to preserve circulatory homeostasis at a time when the principal cause of a low cardiac output was intravascular volume depletion. Angiotensin II supported systemic BP by direct systemic vasoconstriction, by facilitating the central and peripheral effects of the sympathetic nervous system, by promoting renal sodium retention by the production of aldosterone, and by increasing total body water by enhancing thirst and the synthesis of vasopressin. In addition, angiotensin II evolved as an important mechanism to preserve the glomerular filtration rate in low-flow states. These actions of angiotensin II were beneficial when the system first evolved, but its activation in patients with heart failure not only fails to reverse the low-output state but further exacerbates loading conditions in the left ventricle, thereby leading to worsening heart failure. Moreover, increased levels of angiotensin II cause heightened sympathetic nervous activity, potassium depletion, and hyponatremia, each of which can lead to further clinical deterioration. Therefore, activation of the renin-angiotensin system in heart failure might appear (at first) to be a maladaptive response. Recent evidence, however, suggests that this hormonal system continues (even in heart failure) to carry out the primary functions for which it was designed. Angiotensin II plays an important role in preserving systemic BP and in preserving the glomerular filtration rate as renal artery pressure and renal blood flow decline; in addition, by stimulating the synthesis of aldosterone, the renin-angiotensin system provides an important role for potassium disposal.(ABSTRACT TRUNCATED AT 250 WORDS)