CORTICOSTEROID ANTAGONISM OF THE POSITIVE INOTROPIC EFFECT OF OUABAIN

¹ Department of Physiology, University of Virginia School of Medicine, Charlottesville, Virginia

A variety of corticosteroids were evaluated as ouabain antagonists in the isolated cat papillary muscle preparation. Aldosterone, 2-methyl 9-fluorocortisol, deoxycorticosterone, 9-fluorocortisol, dexamethasone and corticosterone antagonized the positive inotropic effect of ouabain at 37°C in low-calcium buffer. Cortisol, Reichstein’s Substance S, 11-dehydrocorticosterone, prednisolone and 6-methylprednisolone did not antagonize ouabain. At concentrations much higher than those of other effective corticosteroids, progesterone also antagonized ouabain. However, this antagonism occurred after a large negative inotropic effect and probably represents a toxic response. At 27°C aldosterone failed to antagonize ouabain, but at this lower temperature aldosterone exerted a much greater positive inotropic effect than at 37°C. A dual receptor mechanism hypothesis is offered to explain tentatively both the inotropic and anti-ouabain effects of aldosterone.

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