POSITIVE INOTROPIC EFFECT OF CARDIOTONIC STEROIDS: DIFFERENTIAL ANTAGONISM BY ALDOSTERONE

¹ Department of Pharmacology, Schools of Medicine and Pharmacy, University of Washington, Seattle, Washington

The influence of aldosterone on the positive inotropie effect of several cardiotonic steroids was investigated. In isolated, electrically driven rabbit atria, aldosterone (10^-5 M) antagonized the inotropic effect of the cardiac glycosides ouabain and strophanthin when the initial contractile tension was low, viz., when atria were driven at low frequency or were exposed to low calcium (0.63 mM) medium. At a frequency of 2/sec in normal calcium (2.54 mM) medium, aldosterone failed to antagonize the positive inotropic effect of the glycosides. An inverse relation was noted between the calcium concentration and the antagonism produced by aldosterone. Under conditions identical to those in which aldosterone antagonized the glycosides, there was no antagonism of the inotropic effect of the aglycones strophanthidin and acetylstrophanthidin or of the catecholamine isoproterenol. Aldosterone stimulation of sodium transport in tissues such as kidney is generally thought to be dependent on protein synthesis and is not readily reversible. By contrast, aldosterone antagonism of glycoside inotropism seen in this study could be abolished by washing the tissues in aldosterone-free solution. Thus, aldosterone-induced stimulation of active sodium transport, as it occurs in renal tissue, does not appear to be necessary for antagonism of glycoside inotropism. The lack of effect on isoproterenol and aglycone inotropism, plus the antagonism of glycoside inotropism, suggest that the action of aldosterone may be selective for glycosides. The results are compatible with the interpretation that aldosterone may interfere with access of glycosides. but not of aglycones, to the digitalis inotropic receptor.