The antagonistic effects of ouabain and calcium channel blockers on the contractility of the isolated rat heart.
The simultaneous prescription of a calcium channel blocker and a cardiac glycoside is a frequently used therapeutic combination in cardiology, although its consequences on inotropism have not been really evaluated. This association is studied on isolated rat heart perfused at constant coronary pressure, paced at a constant frequency and working against a left intraventricular balloon. Since the inotropic effects are dependent on the basic level of myocardium contractility, controls were made hypocontractile by lowering external calcium level to 0.25 mM. For the same initial systolic pressure (45 mm Hg) and + dP/dTmax (150 mm Hg X s-1) the inotropic effect of 10(-5) M ouabain was significantly less pronounced in the presence of 10(-6) M verapamil or 10(-7) M nifedipine at 2.5 mM CaCl2 than at the low external calcium concentration of 0.25 mM (increasing the + dP/dtmax by 35% +/- 4, 29% +/- 6 and 110% +/- 18 respectively). Since we know that the inotropic properties of digitalis are probably due to an increase of the slow calcium inward current, we conclude that the observed effect would be due to a blockade of these channels by calcium blockers.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D004336:Drug Antagonism; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010042:Ouabain; D014700:Verapamil; D009543:Nifedipine; D002122:Calcium Chloride