Sodium and water retention in heart failure: pathogenesis and treatment

In congestive heart failure (CHF), low cardiac output decreases the fullness of the arterial circulation. This underfilling of the arterial vascular compartment unloads the baroreceptors, resulting in a sequence of events to maintain arterial circulatory integrity. Among them, the renin-angiotensin-aldosterone axis, the sympathetic nervous system, the non-osmotic release of vasopressin and the endothelins are activated to increase vascular resistance and enhance sodium and water renal retention. Simultaneously, vasodilatory and natriuretic substances such as the natriuretic peptides are activated to counterregulate these vasoconstrictors. In the initial phase of CHF, these events contribute to the cardiorenal adaptation. However, when CHF progresses, they become maladaptive and further depress vantricular performance and increase sodium and water retention. This vicious cycle of CHF provides the rationale for the use of neurohormonal antagonists in CHF. The beneficial effects of angiotensin converting enzyme inhibitors in CHF are well described. Vasopressin V1 receptor antagonists have been associated with peripheral vasodilation and improved cardiac function in some patients with CHF. In CHF animals, the vasopressin V2 receptor antagonist has been demonstrated to reverse the defect in water excretion. Bosentan, an endothelin antagonist, is associated with an increase of cardiac index in patients with CHF. A role for exogenous natriuretic peptides is also under investigation. Modulation of the neurohumoral systems associated with CHF opens a new perspective in the treatment of cardiac edema, principally by improving cardiac performance.