Vasopressin receptor antagonists: Mechanisms of action and potential effects in heart failure

ABSTRACT

Increased arginine vasopressin (AVP) secretion in heart failure may lead to vasoconstriction, left ventricular remodeling, and water retention—actions that promote afterload, preload, and hyponatremia and thereby cause disease progression. Interfering with AVP-mediated signaling pharmacologically may be beneficial in heart failure. Selective antagonism of the vasopressin 2 (V₂) receptor may facilitate a safe diuresis and normalize low serum sodium levels, as demonstrated in preliminary clinical trials. Pure V₂ antagonism, however, may stimulate AVP secretion and enhance V_1a signaling, while pure V_1a receptor antagonism may lead to unwanted V₂ stimulation and secondary water retention and volume expansion. Combined V_1a and V₂ receptor antagonism could potentially prove advantageous as a therapy for heart failure by acting synergistically to facilitate diuresis and improve hemodynamics.