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, I n this study, organ accumulation of orally administered [H-3]ouabain w as examined in rats. Exogenous [H-3]ouabain was accumulated in high le vels in the adrenals, especially in the zona intermedia, and was not m etabolized in the rat, Accumulated [H-3]ouabain mimicked the movement of ''endogenous'' digitalis-like factor, since 1) the plasma [H-3]ouab ain level decreased in bilaterally adrenalectomized rats, 2) the plasm a [H-3]ouabain level increased accompanied by a decrease in [H-3]ouaba in content in the adrenals in reduced renal mass hypertensive rats, an d 3) [H-3]ouabain levels in plasma and in the adrenals increased in sp ontaneously hypertensive rats, as compared with those in respective co ntrol animals. Moreover, the rat diet contained a relatively high amou nt of ouabain-like immunoreactivity (OLI), and the ratio of the [H-3]o uabain content to OLI in each organ was comparable to that of the dail y intake of dietary [H-3]ouabain to OLI. Furthermore, high H-3-radioac tivities 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 i n the adrenals and, at least in part, act as ''endogenous'' digitalis- like factor(s).