Vasopressin receptor antagonists. Therapeutic potential in the management of acute and chronic heart failure.
Despite the use of ACE inhibitors and beta-blockers, the morbidity and mortality of patients with chronic heart failure remains quite high. This has stimulated the development of new therapies, many based on the neurohormonal hypothesis. There are now multiple agents being developed for the treatment of heart failure designed to block many of the neurohormones that are increased in these patients. One of the hormones that is increased in chronic heart failure is vasopressin. Vasopressin reduces free water secretion and at high concentrations, causes vasoconstriction in the peripheral vasculature. Antagonists to vasopressin will promote free water excretion (aquaresis) and vasodilatation with a subsequent reduction in afterload. In theory, these agents would be beneficial for both acute exacerbations of heart failure (free water excretion) and chronic heart failure (neurohormonal blockade). We review the potential uses of these antagonists for these two conditions and the promising results of small, hemodynamic trials with the new vasopressin antagonists that have already been performed.
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