Tolvaptan, a novel, orally active, selective, nonpeptide antagonist that blocks arginine vasopressin from binding to V2 receptors of the distal nephron, induces the excretion of electrolyte-free water without changing the total level of electrolyte excretion.10 In patients with heart failure, tolvaptan appears to decrease body weight and edema and increase serum sodium concentrations without adversely affecting serum electrolyte levels,
vital signs, or renal function. We report the results of two randomized, placebo- controlled, double-blind phase 3 studies (Study of Ascending Levels of Tolvaptan in Hyponatremia 1 and 2 [SALT-1 and SALT-2]) examining the effect of tolvaptan on hypervolemic and euvolemic hyponatremia of diverse causes. These trials assessed the outpatient use of a vasopressin V2-receptor antagonist for hyponatremia of diverse origin, including assessments of reversibility and safety.