Comparative study of coronary vasodilator and cardiac effects of nitrendipine by use of isolated, blood-perfused dog heart preparations.

The coronary vasodilator and cardiac effects of 3-ethyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl) -3,5-pyridinedicarboxylate (nitrendipine, Bay e 5009) were compared in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node and papillary muscle preparations of dogs with i.a. administration. In all preparations nitrendipine increased (coronary) blood flow. In SA node preparations nitrendipine reduced sinus rate but the reduction remained only about 13% of the basal value even at the highest dose. The dose estimated to produce a 15% (nearly a half maximum) decrease in sinus rate was about 8 times the dose which doubled coronary blood flow. In AV node preparations nitrendipine prolonged AV conduction time when injected into the artery supplying the AV node but the prolongation remained only about 12% of the basal value even at the highest dose. The dose estimated to produce a 15% (nearly a half maximum) increase in AV conduction time was about 11 times the dose which doubled coronary blood flow. When injected into the artery supplying the His-Purkinje ventricular system of AV node preparations, nitrendipine was entirely ineffective on AV conduction. In paced papillary muscle preparations nitrendipine reduced force of contraction. The reduction, however, remained less than 50% of the basal value even at the highest dose. The dose estimated to reduce force of contraction by half was about 11 times the dose which doubled coronary blood flow. Nitrendipine was entirely ineffective on ventricular beating rate of spontaneously beating papillary muscle preparations. These results indicate that nitrendipine is highly vasoselective, and warrant its high efficacy as an antianginal drug.