Adenosine inhibits the positive chronotropic and inotropic responses to norepinephrine and Bay k 8644 in the isolated, blood-perfused dog atrium.
We investigated the effects of adenosine on the positive chronotropic and inotropic responses to an endogenous catecholamine (norepinephrine), a beta 1-adrenoceptor agonist (dobutamine), an adenylate cyclase activator (forskolin), a phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, IBMX) and a calcium channel agonist (Bay k 8644) in the isolated, blood-perfused dog atrium. Each drug was injected into the sinus node artery of the isolated atrium. Adenosine infusions at low (45 or 90 nmol/min) and high (184 or 450 nmol/min) doses induced a dose-dependent decrease of sinus rate and atrial contractile force. The positive chronotropic and inotropic responses to norepinephrine, dobutamine and forskolin were dose-dependently depressed by adenosine. IBMX- and Bay k 8644-induced positive cardiac responses were also inhibited by adenosine at high doses but not at low doses. These results suggest that adenosine attenuates calcium channel-dependent as well as cyclic AMP-dependent positive chronotropic and inotropic responses to cardiostimulants in the isolated dog atrium.
Furukawa
Y
Y
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Akahane
K
K
Haniuda
M
M
Chiba
S
S
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004280:Dobutamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects
D005576:Colforsin; D004280:Dobutamine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine