Indapamide accentuates cardiac chronotropic responses to epidermal growth factor in chick cardiomyocytes

We have previously shown that indapamide [chloro-4-N-(methyl-2-indolinyl-1)-sulfamoyal-3-benzamide] has a direct action on the heart to alter ion fluxes. This study sought to examine the potential interaction between indapamide and epidermal growth factor (EGF). Cardiomyocytes were prepared as primary culture from 7-day-old chick embryo hearts as aggregates that have a pattern of consistent spontaneous contraction. Indapamide enhanced the positive chronotropic response to EGF observed in chick embryonic ventricular myocyte aggregates while indapamide itself did not alter cardiac contractile frequency. Taken in conjunction with data that calcium channel blockade, inhibition of sodium entry or Na(+)-Ca2+ exchange in the cardiomyocyte opposes the positive chronotropic action of EGF on the cardiomyocyte, this study has identified an agent, indapamide, that accentuates the cardiomyocyte response to EGF.