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 [3H]ouabain was examined in rats. Exogenous [3H]ouabain was accumulated in high levels in the adrenals, especially in the zona intermedia, and was not metabolized in the rat. Accumulated [3H]ouabain mimicked the movement of "endogenous" digitalis-like factor, since 1) the plasma [3H]ouabain level decreased in bilaterally adrenalectomized rats, 2) the plasma [3H]ouabain level increased accompanied by a decrease in [3H]ouabain content in the adrenals in reduced renal mass hypertensive rats, and 3) [3H]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 [3H]ouabain content to OLI in each organ was comparable to that of the daily intake of dietary [3H]ouabain to OLI. Furthermore, high 3H-radioactivities were also observed in the adrenals of rats that ingested [3H]digoxin and [3H]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).
Kitano
S
S
Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
Morimoto
S
S
Nishibe
A
A
Fukuo
K
K
Hirotani
A
A
Nakahashi
T
T
Yasuda
O
O
Ogihara
T
T
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D000315:Adrenalectomy; D000818:Animals; D001345:Autoradiography; D002298:Cardenolides; D002316:Cardiotonic Agents / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003429:Cross Reactions; D004074:Digitoxin / Q000097:blood / Q000493:pharmacokinetics; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy; D007668:Kidney / Q000737:chemistry / Q000473:pathology / Q000601:surgery; D007700:Kinetics; D009392:Nephrectomy; D010042:Ouabain / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012503:Saponins / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
D002298:Cardenolides; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D012503:Saponins; C034504:digoxin-like factors; D014316:Tritium; D010042:Ouabain; D004077:Digoxin; D004074:Digitoxin