Cardiovascular profiles of the calcium antagonists nisoldipine and nifedipine in the blood-perfused dog heart.
The coronary vasodilator and cardiac effects of nisoldipine (Bay k 5552) were compared with those of nifedipine in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node and papillary muscle preparations of dogs with i.a. administration. Principally all preparations received both nisoldipine (0.01-10 micrograms) and nifedipine (0.3-3 micrograms). In all preparations both drugs increased (coronary) blood flow, and in this respect they were nearly equipotent. In SA node preparations nisoldipine reduced sinus rate and produced atrial standstill in large doses. Nifedipine also reduced sinus rate in the dose range tested. In this respect, too, both drugs were nearly equipotent. The ratio of the dose that produces a 15% (nearly half-maximum) decrease in sinus rate to the dose that doubles coronary blood flow was about 7 for nisoldipine and about 9 for nifedipine. In AV node preparations both nisoldipine and nifedipine prolonged AV conduction time and produced second- or third-degree AV block in large doses only when injected into the artery supplying the AV node but not into the artery supplying the His-Purkinje-ventricular system. In suppressing AV nodal conduction both drugs were nearly equipotent. The ratio of the dose that produces a 15% (nearly half-maximum) increase in AV conduction time to the dose that doubles coronary blood flow was about 3.3 for nisoldipine and about 5 for nifedipine. In paced papillary muscle preparations both nisoldipine and nifedipine reduced the force of contraction. In this respect, too, both drugs were nearly equipotent. The ratio of dose that reduces the force of contraction by half to the dose that doubles coronary blood flow was about 5 for both of them.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015737:Nisoldipine; D012849:Sinoatrial Node / Q000187:drug effects
D002121:Calcium Channel Blockers; D015737:Nisoldipine; D009543:Nifedipine