Pharmacological analysis of chrono- and inotropic responses to diazepam in the isolated, blood-perfused canine atrium.
Effects of diazepam on the pacemaker activity and atrial contractility were investigated using the isolated and blood-perfused canine atrium. When diazepam in a dose range of 3-300 micrograms was injected directly into the sinus node artery, biphasic (negative followed by positive) chrono- and inotropic responses were dose-relatedly evoked. These responses were not affected by atropine in a dose which blocked ACh-induced negative ones. Propranolol inhibited positive chrono- and inotropic responses to diazepam, and prolonged the duration of the negative responses. Imipramine, in a dose which blocked tyramine-induced positive responses, significantly augmented the positive inotropic responses to diazepam. From these results, it is suggested that diazepam induces direct negative chrono- and inotropic effects, the mechanism of which remains to be defined, and indirect positive effects by catecholamine release from the sympathetic nerve terminals, though not mediated by a tyramine-like action. Diazepam tended to potentiate negative chrono- and inotropic effects of adenosine but not significantly, suggesting that diazepam plays a minor role as an adenosine potentiator in the dog right atrium.
Akahane
K
K
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Furukawa
Y
Y
Ogiwara
Y
Y
Haniuda
M
M
Takeda
M
M
Chiba
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
D001285:Atropine; D011433:Propranolol; D000241:Adenosine; D000109:Acetylcholine; D007099:Imipramine; D003975:Diazepam; D009638:Norepinephrine; D014439:Tyramine