Comparison of the effects of nifedipine, diltiazem and verapamil on the mechanical activity of rabbit papillary muscles induced by barium chloride.

Isolated rabbit papillary muscles that do not present pacemaker activity under physiological conditions develop a spontaneous activity in the presence of 2 mmol/l BaCl2. Ba-induced contractions were unaffected by high concentrations of the Na antagonist procainamide (10(-5) mol/l). Tetrodotoxin (10(-5) mol/l), a specific blocker of the fast Na current, only slightly increased the amplitude of contractions. In contrast, the calcium entry blockers nifedipine, diltiazem, and verapamil strongly depressed the mechanical activity in a time- and dose-dependent manner. The concentrations that decreased the amplitude and frequency of contractions by 50% were determined. The order of potency was nifedipine much greater than diltiazem greater than or equal to verapamil. Ba-induced automaticity is a particularly useful model on which the potency of calcium entry blockers could be assessed.