A strain dependent sex difference in ouabain-induced cardiotoxicity in rats

Male rats of the BDIX strain were about twice as sensitive to the lethal effects of intravenously infused ouabain than were their female counterparts. This sex difference in ouabain sensitivity was not exhibited by rats of the Wistar strain. In bile duct-cannulated animals, ouabain biliary excretion was much faster in female BDIX rats. This finding could partly explain the greater ouabain resistance, although certain aspects of the cardiac/plasma ouabain concentration data did suggest that there may have been a component of the sex-related resistance that was not explicable on a pharmacokinetic basis. The faster ouabain biliary excretion in female rats could also partly explain the fact that for similar rates of infusion, the plasma ouabain concentration during infusion was similar in both sexes, despite the body size of the female rats being about one-third smaller.