Vasopressin and Vasopressin Receptor Antagonists in Heart Failure

Antidiuretic hormone, also known as arginine vasopressin, is a hormone with a multitude of physiologic activities including the control of urinary free water excretion. Antidiuretic hormone also plays a role in vasoconstriction and has 3 receptors that have been identified. Vasopressin analogs and antagonists have been extensively studied in animal models as well as in humans. Because heart failure is associated with a state of water retention, several vasopressin antagonists have been evaluated for their potential aquaretic effect. Diuretics remain the mainstay of treatment in acute and chronic volume overload but are not shown to improve survival. In fact, they are associated with numerous side effects including hypotension, electrolyte abnormalities, worsening renal function, and activation of renin-angiotensin-aldosternone system. Tolvaptan, conivaptan, and lixivaptan are some of the vasopressin antagonists that have been studied in heart failure. The results were initially encouraging with alleviation of symptoms and effective aquaresis without worsening of hyponatremia or renal function, but yet failed to show any effect on mortality in heart failure. With an increasing number of more selective orally active vasopressin antagonists, further studies are underway to establish the role of Vaptans in the treatment of heart failure and other disease states with volume overload and hyponatremia.