Exogenous ouabain is accumulated in the adrenals and mimics the kinetics of endogenous digitalis-like factor in rats

Ouabain has been isolated as an endogenous pathogenetic factor in salt induced hypertension and has been shown to be rich in the adrenals, In this study, organ accumulation of orally administered [H-3]ouabain was examined in rats. Exogenous [H-3]ouabain was accumulated in high levels in the adrenals, especially in the zona intermedia, and was not metabolized in the rat, Accumulated [H-3]ouabain mimicked the movement of "endogenous" digitalis-like factor, since 1) the plasma [H-3]ouabain level decreased in bilaterally adrenalectomized rats, 2) the plasma [H-3]ouabain level increased accompanied by a decrease in [H-3]ouabain content in the adrenals in reduced renal mass hypertensive rats, and 3) [H-3]ouabain levels in plasma and in the adrenals increased in spontaneously hypertensive rats, as compared with those in respective control animals. Moreover, the rat diet contained a relatively high amount of ouabain-like immunoreactivity (OLI), and the ratio of the [H-3]ouabain content to OLI in each organ was comparable to that of the daily intake of dietary [H-3]ouabain to OLI. Furthermore, high H-3-radioactivities were also observed in the adrenals of rats that ingested [H-3]digoxin and [H-3]digitoxin. These data suggest that exogenous ouabain, related cardiotonic glycosides of plant origin, or both accumulate in the adrenals and, at least in part, act as "endogenous" digitalis-like factor(s).