Lack of interaction of spironolactone with ouabain guinea pig isolated heart muscle preparations.

The effect of spironolactone on ouabain action was studied in experiments on guinea pig isolated heart muscle preparations. There was no effect of spironolactone on the ouabain-induced positive inotropic or toxic effects in isolated papillary muscles. This was accompanied by a lack of spironolactone effect on myocardial ouabain uptake. Only rather high spironolactone concentrations (1 X 10(-4) M) led to a reduced cardiac ouabain uptake (about 10%). The subcellular distribution pattern of ouabain, however, remained unchanged under these conditions. Studies on ouabain binding to a cardiac NaK-ATPase supported the conclusion that a direct interaction of spironolactone and cardiac glycosides at the myocardium could be ruled out.