SODIUM AND WATER-RETENTION IN HEART-FAILURE - PATHOGENESIS AND TREATMENT

In congestive heart failure (CHF), low cardiac output decreases the fu llness of the arterial circulation. This underfilling of the arterial vascular compartment unloads the baroreceptors, resulting in a sequenc e of events to maintain arterial circulatory integrity. Among them, th e renin-angiotensin-aldosterone axis, the sympathetic nervous system, the non-osmotic release of vasopressin and the endothelins are activat ed to increase vascular resistance and enhance sodium and water renal retention. Simultaneously, vasodilatory and natriuretic substances suc h as the natriuretic peptides are activated to counterregulate these v asoconstrictors. In the initial phase of CHF, these events contribute to the cardiorenal adaptation. However, when CHF progresses, they beco me maladaptive and further depress vantricular performance and increas e sodium and water retention. This vicious cycle of CHF provides the r ationale for the use of neurohormonal antagonists in CHF. The benefici al effects of angiotensin converting enzyme inhibitors in CHF are well described. Vasopressin V1 receptor antagonists have been associated w ith peripheral vasodilation and improved cardiac function in some pati ents with CHF. In CHF animals, the vasopressin V2 receptor antagonist has been demonstrated to reverse the defect in water excretion. Bosent an, an endothelin antagonist, is associated with an increase of cardia c index in patients with CHF. A role for exogenous natriuretic peptide s is also under investigation. Modulation of the neurohumoral systems associated with CHF opens a new perspective in the treatment of cardia c edema, principally by improving cardiac performance.