Ouabain and Endogenous Ouabain -Dr. Jekyll and Mr. Hyde of Cardiac Glycosides?

In current research reports several disease states are claimed to be associated with elevated levels of endogenous ouabain. These include hypertension, cardiac enlargement, cardiac and renal failure, and a variety of terminal disorders. It has been suggested that endogenous ouabain should be considered as a major contributor to increased blood pressure and overall cardiovascular risk. These hypotheses stand in stark contrast to decades of clinical experiences with ouabain in humans, which indicate that plant-derived ouabain is effective in treating heart failure. In patients with hypertension ouabain lowers blood pressure. These conclusive clinical experiences refute the hypothesis that ouabain in humans is a major contributor to increased blood pressure and overall cardiovascular risk. The pronounced dependence of the ouabain effects on the dose, the state of the autonomic nervous system and species-specific characteristics in pharmacokinetics may explain many of the conflicting research results that have been published on experiments with ouabain. Rodents have different sensitivities to cardiac glycosides than humans. Pharmacokinetics of cardiac glycosides in rodents are also different from humans. Therefore, caution is advised when extrapolating experimental results in rodents to humans. The mutually exclusive effects of ouabain and the endogenous inhibitor of the Na/K-ATPase observed in mammalian tissues do not support the hypothesis that this inhibitor is identical with ouabain, but favour the interpretation that De Wardener’s “third factor” is something different, which also reacts to ouabain antibodies.