Decrease in time to peak tension produced by calcium blockers and isoproterenol. Its dependence on extracellular calcium.

The present experiments were designed to analyze the effect of verapamil, nifedipine and isoproterenol on myocardial contractility (+dT/dtmax) and time to peak tension (TTP) and its dependence on extracellular calcium concentration (Ca2+). The experiments were performed on cat papillary muscles from reserpinized cats. At (Ca2+) 1.34 mM the negative inotropic effect of cumulative doses of verapamil and nifedipine and the positive inotropic effect of isoproterenol occurred associated with a significant and dose-dependent decrease in TTP. The decrease in TTP produced by calcium blockers was completely reversed by the addition of calcium in a close parallelism with the recovery in myocardial contractility: At (Ca2+) 1.34 mM; verapamil 10(-6)M significantly decreased TTP from 299 +/- 14 msec to 250 +/- 11 msec. At (Ca2+) 15 mM values for TTP were 285 +/- 7 msec (control) and 291 +/- 5 msec (verapamil). Nifedipine 5 X 10(-7) M decreased TTP from 343 +/- 20 msec to 246 +/- 4 msec (Ca 1.34 mM). Values of TTP at calcium 15 mM were 296 +/- 6 msec (control) and 300 +/- 17 msec (nifedipine). On the contrary, the significant decrease in TTP produced by isoproterenol 10(-5)M at (Ca2+) 1.34 from 266 +/- 14 msec to 222 +/- 14 msec was still present at (Ca2+) 15 mM: 233 +/- 8 msec (control) and 220 +/- 8 msec (isoproterenol). The results suggest that the decrease in TTP produced by calcium blockers and isoproterenol is mediated by different mechanisms.