Treating hyponatremia in heart failure

Hyponatremia is common and associated with adverse outcomes in patients with congestive heart failure (CHF). In many patients who have CHF with hyponatremia, plasma arginine vasopressin (AVP) is elevated inappropriately. AVP causes water retention by interacting with V₂ receptors in the renal collecting duct, leading to dilutional hyponatremia and increased ventricular preload. AVP also may contribute to pathophysiologic process in CHF by interacting with V_IA receptors on vascular smooth muscle cells and myocytes. The potential utility of AVP antagonists - V₂ antagonists and dual V_IA/V₂ antagonists - in correcting hyponatremia and relieving the congestion and edema associated with CHF is being actively explored. Combined antagonists may offer additional benefit by interfering with excessive V_IA signaling. Unlike diuretics, which increase urine volume and electrolyte excretion, AVP antagonists of these types produce an aquaresis characterized by an increase in free water clearance concomitant with sparing of electrolytes. Studies in experimental CHF as well as preliminary clinical trials with selective and nonselective V₂ antagonists have been encouraging, suggesting that these agents may hold promise for treatment of hyponatremia in CHF.