Effects of denopamine on rat myocardium in comparison with isoprenaline.
The adverse effects of denopamine (TA-064) were investigated on rat myocardium in comparison with those of isoprenaline (isoproterenol). Experiment 1. Rats were treated with isoprenaline (10 mg/kg) or denopamine (10 mg/kg) once by subcutaneous injection. 15 h after drug administration, rat hearts were isolated, and heart mitochondria were prepared. Activities of three portions of electron transport chain (NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase) of mitochondria were measured. In rats treated with isoprenaline, significant decreases in NADH-cytochrome c reductase and cytochrome c oxidase activities were observed. While, in rats treated with denopamine, NADH-cytochrome c reductase activity was not decreased significantly, and decrease in cytochrome c oxidase activity was less than that observed in the isoprenaline group. Experiment 2. Rats were treated with isoprenaline (10 mg/kg) or denopamine (10 mg/kg) by subcutaneous injection once a day for 6 successive days. After the last drug administration, hearts were isolated, and cardiac membranes were prepared. Numbers of beta-adrenergic receptors were measured using 3H-dihydroalprenolol. In rats treated with isoprenaline, a significant decrease in the number of beta-adrenergic receptors was observed. On the contrary, administration of denopamine did not affect significantly the number of beta-adrenergic receptors.
Sugiyama
S
S
Department of Biomedical Chemistry, University of Nagoya, Japan.
Hanaki
Y
Y
Hayashi
K
K
Ozawa
T
T
D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism
D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D007545:Isoproterenol; C037293:denopamine