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.