ANTI-OUABAIN ACTION OF STEROID HORMONES ON TWITCH AND POTASSIUM CONTRACTURE IN HEART VENTRICLE STRIP OF FROG

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Mechanism as to the positive inotropic action of cardiac glycosides at the cellular level is still a matter of speculation. It could, however, be said that the high energy phosphates which are involved in energy production, do not appear to be implicated in the action of the glycosides (1-3). Action of the glycosides on electrolyte exchange process has been intensively investigated. But a therapeutic effect of ouabain has been shown to occur without any changes in transmembrane- and action potential (4-6). Therefore, the possibility that the positive inotropic action takes place on the basis of change in sodium and/or potassium metabolism appears to be also unlikely. Nayler pointed out in her recent review (7) that the most interesting findings on electrolyte and the glycosides would be those on calcium. Many recent reports (8-10) suggest an intimate relationship between the glycosides action and intracellular calcium, which takes an essential part in the activation and the maintenance of the contractile process (11, 12).<BR> Kuffler and Huxley (13, 14) reported that the first step in the process of muscular contraction is the depolarization of excitable membrane; therefore, twitch and potassium contracture are essentially the same with respect to initiation of the contractile process. Thus, the first series of events in the production of both responses consists of depolarization and the following initiation of linking process, through which ionized calcium is released within cell. Hodgkin and Horowicz (15) examined precisely the relation between contractile tension development and the change in the membrane potential given by various external potassium concentrations and determined a mechanical threshold of membrane potential for initiation of contractile apparatus. Otsuka and Nonomura (16) studied the influence of ouabain on such a relation between membrane potential and contractile tension development in the frog heart and showed that the cardiac glycoside alters the relation so that a smaller depolarization is required for the development of a given tension.<BR> Our attention was paid to the findings. In the present report, a series of such an experiment has been, done, and that in the presence of various steroid hormones: because, several reports showed that some mineralocorticoids have anti-ouabain action on ion-transport of human erythrocyte (17), contraction of rat aortic strip (18) and potassium out-flux of guinea pig heart (19). In the first series of present study, anti-ouabain action of aldosterone on both twitch and potassium-induced contracture and on the relation between membrane potential and developed tension was investigated in frog heart. Then, anti-ouabain action of other corticoids and some sexual hormones was studied and anti-ouabain potency of these steroid hormones was compared to that of aldosterone. Results obtained demonstrate that the corticoids tested and some sexual hormones can inhibit the positive inotropic action of ouabain so that the shift of mechanical threshold of membrane potential by ouabain is cancelled partially or almost completely by these steroid hormones.
公益社団法人日本薬理学会の論文

ANTI-OUABAIN ACTION OF STEROID HORMONES ON TWITCH AND POTASSIUM CONTRACTURE IN HEART VENTRICLE STRIP OF FROG

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