Indapamide alters the cyclic AMP signal transduction pathway in cardiomyocytes in culture

Abstract

The cellular mechanism of action on the heart of the antihypertensive/diuretic agent indapamine is uncertain. Because of the importance of cAMP in signal transduction in the heart, the present study was designed to examine the hypothesis that indapamide interacts with the cAMP signal transduction pathway. Ventricular cardiomyocytes were isolated from 7-day-old chick embryo hearts and were maintained in culture. Indapamide did not alter basal and isoproterenol-stimulated cAMP levels in cardiomyocytes. However, indapamide pretreatment markedly accentuated forskolin-stimulated cAMP production. It also accentuated cholera toxin-induced increases in cAMP. Thus these data indicate that indapamide has an effect directly on the heart as manifested by its action on the ventricular cardiomyocytes. An effect of indapamide on cAMP generation by cholera toxin and forskolin suggests both a direct effect on adenylyl cyclase as well as an action through G s. These findings may provide a cellular mechanism of action explaining indapamide's effect on the heart.