Inhibitory effects of diltiazem, verapamil, nifedipine, and nicardipine on sympathetic tachycardia in decentralized hearts of anesthetized dogs.
Intravenous diltiazem (10-300 micrograms/kg), verapamil (10-300 micrograms/kg), nifedipine (1-100 micrograms/kg) and nicardipine (1-100 micrograms/kg) inhibited the tachycardia caused by cardiac sympathetic nerve stimulation (SNS, 0.5-4 Hz) in decentralized hearts of anesthetized dogs. The dose range of each drug required to inhibit the SNS-induced tachycardia was almost equivalent to that required to produce the increase in coronary blood flow and the decrease in blood pressure. Nifedipine and nicardipine were equi-active and about 10 times more potent than diltiazem and verapamil in inhibiting the SNS-induced tachycardia. They produced a slight but dose-dependent slowing of the resting heart rate. The negative chronotropic potency was approximately nicardipine, verapamil greater than nifedipine, diltiazem. Bay K 8644 (30 micrograms/kg) antagonized the inhibitory effects of diltiazem (100 micrograms/kg) and nifedipine (30 micrograms/kg) on the SNS-induced tachycardia. Tachycardia induced by intracoronary norepinephrine (0.03-0.3 micrograms) was suppressed by diltiazem (30-300 micrograms/kg) and nifedipine (10-100 micrograms/kg). The inhibitory effects of calcium entry blocking drugs on the sympathetic tachycardia appear to be explained by the interference of the beta-adrenoceptor-mediated increase in slow inward current in the sinoatrial (SA) node. It is also suggested that other mechanisms different from calcium entry blocking action contribute to the negative chronotropic response to these calcium entry blocking drugs.
Satoh
E
E
Department of Pharmacology, Tohoku University, Sendai, Japan.
Mukaiyama
O
O
Kimura
T
T
Satoh
S
S
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology*; D010424:Pentobarbital / Q000008:administration & dosage; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013610:Tachycardia / Q000209:etiology / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D010424:Pentobarbital; D009543:Nifedipine