Comparison of indapamide and hydrochlorothiazide on spontaneous contraction of cardiomyocytes in culture: the effect on alterations of extracellular calcium or potassium.

1. The purpose of this study was to determine whether indapamide or hydrochlorothiazide had a direct action on the heart, specifically to determine whether either diuretic affected spontaneous contractile function of cardiomyocytes in culture or altered the response to increases in extracellular potassium or calcium. 2. Chick embryonic ventricular cells were cultured from 7-day-old chick embryo and myocardial cell aggregates were prepared. Spontaneous cardiac contractile frequency of ventricular myocyte aggregates was monitored. Indapamide [chloro-4-N-(methyl-2-indolinyl-1)-sulfamoyal-3-benzamide] over a concentration range of 10(-9)-10(-6) M did not alter cardiac contractile frequency. 3. Indapamide, in a dose dependent manner, significantly (P < 0.05) antagonized the effect of increases in extracellular potassium [K+]0 that produced a concentration dependent reduction in cardiac contractile frequency. In contrast, hydrochlorothiazide accentuated the effect of increased [K+]0 while hydrochlorothiazide did not alter spontaneous contractile frequency at the usual [K+]0 of 2.0 mM. 4. Indapamide produced a significant (P < 0.05) reduction in the effect of increases in extracellular calcium [Ca2+]0 on cardiac contractility while hydrochlorothiazide was associated with a slight accentuation of the effect of increased [Ca2+]0. Indapamide also slightly reduced the effect of the calcium agonist Bay K 8644, which increases intracellular calcium through voltage operated calcium channels. 5. These data indicate that diuretics modulate a cardiac response to changes in extracellular potassium and calcium. Indapamide antagonizes the effects of increases in extracellular potassium and calcium while hydrochlorothiazide has the opposite effect on the cardiac response to increases in [K+]0 or [Ca2+]0.