Negative inotropic effect of verapamil, nifedipine and prenylamine and its reversal by calcium or isoproterenol.
The type of antagonism between verapamil, nifedipine or prenylamine and calcium or isoproterenol on myocardial contractility, was investigated in cat papillary muscles. Dose response curves to calcium or to isoproterenol were performed in the absence and presence of a single dose of either verapamil, nifedipine or prenylamine. Non significantly different maximum values of tension (T) and maximal rate of rise of tension (+dT/dtmax) were obtained at the "plateau" of the dose responses curves to calcium in the absence and presence of the slow channel inhibitors. The (Ca2+)50, i.e. the calcium concentration necessary to obtain 50% of the maximal effect (T or +dT/dtmax), was significantly greater in the presence of the calcium channel blockers (Lineweaver-Burk method). The decrease in time to peak tension (TTP) associated with the negative inotropic effect of calcium channel blockers was also completely off-set by the addition of extra calcium. A Shild plot with a slope close to the unity confirmed simple competitive antagonism between calcium and nifedipine or prenylamine but not between calcium and verapamil. Isoproterenol was unable to completely overcome the negative inotropic effect of verapamil 10(-5) M and nifedipine 5 X 10(-7) M on T and +dT/dtmax. In addition, it enhanced the decrease in TTP produced by these two calcium entry blockers. The results do not support the view of a competitive antagonism between isoproterenol and verapamil or nifedipine on myocardial contractility. They also indicate that in restoring the decrease in myocardial contractility produced by calcium channel blockers, it is not the same to add extra calcium than isoproterenol.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002415:Cats; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D011299:Prenylamine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014700:Verapamil; D009543:Nifedipine; D011299:Prenylamine; D007545:Isoproterenol; D002118:Calcium