PATHOGENESIS OF SODIUM AND WATER-RETENTION IN CARDIAC-FAILURE

The pathophysiology of sodium and water retention in heart failure is discussed in the context of a unifying hypothesis of body fluid volume regulation. Critical to this hypothesis is the maintenance of arteria l circulatory integrity which can be disturbed by either a reduction i n cardiac output or a fall in systemic vascular resistance secondary t o arterial vasodilatation, as seen in high output heart failure. The f illing of the arterial circulation is sensed by receptors in the left ventricle, carotid artery, aortic arch and renal afferent arteriole. E ffector mechanisms involve non-osmotic vasopressin synthesis and relea se, the reninangiotensin-aldosterone system and the sympathetic nervou s system. In low output heart failure non-peptide selective orally act ive vasopressin V2-receptor antagonists correct the hyponatremia, hypo osmolality, and wafer retention and decrease urinary aquaporin-2 water channels, supporting the role of vasopressin in the wafer retention s een in heart failure. In advanced heart failure aldosterone escape doe s not occur because of diminished distal delivery of sodium which also contributes to the resistance to atrial natriuretic peptide seen in h eart failure. In high output cardiac failure arterial underfilling ass ociated with arterial vasodilation stimulates activation of neurohumor al systems. Tailored specific selective inhibition of these neurohumor al systems, perhaps in combination, may enable more effective treatmen t of cardiac failure.