Specific endogenous Na, K-ATPase inhibitor purified from bovine adrenal.

The endogenous inhibitor of Na, K-ATPase has been implicated in the pathogenesis of salt-induced hypertension. In spite of an intensive search the inhibitor has long remained elusive. We have been able to purify such an inhibitor from methanol extract of bovine adrenal glands by multiple steps of high-performance liquid chromatography (HPLC). This compound with a molecular mass of 336 showed striking similarity to the cardiac glycoside ouabain in its dose dependency in the inhibition of Na, K-ATPase and Na-pump activity, competitive binding to the ouabain-binding site, and dependence of these effects on K+ concentration. These inhibitory activities were potentiated with reduced K+ concentration in parallel with ouabain. These results indicates that vertebrate animals possess a regulator of Na, K-ATPase and suggests the possibility that it may be the mediator of salt-induced high blood pressure.