Is antagonism by Bay k 8644 of the negative dromotropic effect of nifedipine pharmacological?
The dromotropic effect of Bay k 8644 and its interaction with the negative dromotropic effects of nifedipine, verapamil, MnCl2 and tetrodotoxin were investigated by use of isolated, blood-perfused atrioventricular (AV) node preparations of dogs. These agents were injected into the AV node artery. Single injections of Bay k 8644 (0.1-10 micrograms) shortened AV conduction time, but the decrease remained only about 9 msec at 10 micrograms. This effect was not modified by nadolol. Dose-response curves for the negative dromotropic effect of nifedipine were shifted to the right by about 0.5 log units with infusions of Bay k 8644 into the AV node artery at rates of 3 and 10 micrograms/min. A similar shift of dose-response curves to verapamil occurred at 10 micrograms/min of Bay k 8644. However, Bay k 8644 (3 and 10 micrograms/min) failed to modify dose-response curves to MnCl2 and tetrodotoxin. Bay k 8644 (10 micrograms) produced a greater decrease in AV conduction time during the negative dromotropic effect of verapamil (10 or 30 micrograms) and a far greater decrease during the negative dromotropic effect of nifedipine (3 or 10 micrograms) than under control conditions. In contrast, Bay k 8644 (10 micrograms) produced a decrease in AV conduction time nearly to the same extent during the negative dromotropic effect of MnCl2 (10 or 30 mumol) or tetrodotoxin (10 or 30 micrograms) as under control conditions. From these results Bay k 8644 can be described as a rather specific pharmacological antagonist for dihydropyridine slow channel blockers.
Taira
N
N
Wada
Y
Y
Satoh
K
K
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009248:Nadolol; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010477:Perfusion; D011412:Propanolamines / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D011412:Propanolamines; D009248:Nadolol; D008345:Manganese; D013779:Tetrodotoxin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine