Comparison of the effect of amiloride and its analogue dichlorobenzamil on cardiac chronotropic responses to ouabain in myocardial cell aggregates in culture.
The purpose of this study was to compare the effects of amiloride, an inhibitor of Na(+)-H+ exchange, and its analog 3',4'-dichlorobenzamil, a more specific inhibitor of Na(+)-Ca2+ exchange on the response of cardiac myocytes to ouabain. Cardiac myocyte aggregates were prepared from myocytes obtained from 7-day-old chick embryo hearts. Ouabain at 10(-6) M produced a marked and significant (p less than 0.05) reduction in contractile frequency. Amiloride, at 10(-7) to 10(-5) M produced a definite, significant (p less than 0.05) and dose-dependent reduction in this effect of ouabain. In contrast, dichlorobenzamil, 10(-7) to 10(-6) M, significantly (p less than 0.05) accentuated this effect of ouabain. Thus, amiloride and its analog dichlorobenzamil have different effects on the cardiac responses to ouabain presumably because of the differences in the specificity of their inhibition of Na+/H+ and Na+/Ca2+ exchange. Thus to the extent that the effects of amiloride and dichlorobenzamil are mediated through, respectively Na(+)-H+ and Na(+)-Ca2+ exchange, these data suggest that ouabain-induced reduction in contractile frequency is mediated through Na(+)-H+ exchange while Na(+)-Ca2+ exchange acts to minimize this action of ouabain. Amiloride may be useful to oppose the negative chronotropic effect of ouabain while dichlorobenzamil accentuates this effect of ouabain.
Rabkin
S W
SW
Cardiovascular Research Laboratories, University Hospital, Shaughnessy, University of British Columbia, Vancouver, Canada.
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002449:Cell Aggregation; D002478:Cells, Cultured; D002642:Chick Embryo; D006339:Heart Rate / Q000187:drug effects*; D006859:Hydrogen / Q000378:metabolism; D007474:Ion Exchange; D009206:Myocardium / Q000166:cytology; D010042:Ouabain / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology
C041470:3',4'-dichlorobenzamil; D010042:Ouabain; D000584:Amiloride; D006859:Hydrogen; D012964:Sodium; D002118:Calcium