Mechanism of direct cardiostimulating actions of hydralazine.
The vasodilator, hydralazine, was reported to also exert a direct positive inotropic effect on the myocardium at high concentrations. In the present study we investigated the mechanism of this positive inotropic action by using the ventricular myocardium of isolated perfused chick hearts. Hydralazine (10(-3) M) enhanced contractile force and heart rate, and elevated the myocardial cyclic AMP level. To study the Ca2+-dependent slow action potentials, the fast N+ channels were voltage-inactivated with elevated K+ (25 mM), resulting in a loss of electrical excitability. Hydralazine (10(-4) M) rapidly (less than 3 min) allowed the generation of slow action potentials and accompanying contractions by electrical stimulation. These effects of hydralazine were only partially prevented by propranolol. The results suggest that the increase of myocardial contractility produced by hydralazine is the result, at least in part, of a direct effect on the myocardium to increase Ca2+ inflow. The increased Ca2+ influx and inward slow current is due partly to activation of beta-adrenoceptors, with resultant elevation of cyclic AMP, and partly to another mechanism.
D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents; D002645:Chickens; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D006830:Hydralazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011968:Receptors, Histamine / Q000187:drug effects; D014159:Transducers
D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D007473:Ion Channels; D011968:Receptors, Histamine; D006830:Hydralazine; D000242:Cyclic AMP