Effect of digoxin on the in vitro secretion of renin and angiotensin II/III immunoreactivity by the human adrenal gland.
Cardiac glycosides in man inhibit renin secretion, probably through a direct effect at the renal level (i.e. inhibition of juxtaglomerular cell Na/K ATPase). Since there is evidence that the human adrenal possesses an intrinsic renin-angiotensin system, we investigated the effect of digoxin on the in vitro generation of renin and angiotensin II/III, as well as of aldosterone, by the human adrenal gland. Minced normal adrenal tissues were studied in a superfusion system, measuring in the 15-min superfusate fractions active renin by immunoradiometric assay and angiotensin II/III and aldosterone by radioimmunoassay, respectively. In a first set of four experiments using different concentrations of digoxin in sequence for 45 min periods, digoxin 10(-5), but not 10(-8) and 10(-6) mol/l, significantly reduced renin and angiotensin II/III output from adrenals, while no change in aldosterone was observed. In a second set of three experiments, the addition of digoxin 10(-5) mol/l for 120 min caused a sustained reduction of renin and angiotensin II/III, but not of aldosterone. In the final experiment, the decrease of renin and angiotensin II/III during superfusion with digoxin 10(-5) mol/l was significantly greater than that observed during superfusion with digoxin in the presence of antidigoxin antibodies. Our data indicate that digoxin at high doses reduces renin and angiotensin II/III but not aldosterone secretion by the human adrenal gland. This suggests two different effects of digoxin, probably both mediated by inhibition of the Na/K ATPase activity, on the adrenal renin-angiotensin- and aldosterone-secreting cells.
Pistorello
M
M
Institute of Semeiotica Medica, University of Padova, Italy.
Cimolato
M
M
Pedini
F
F
Piovan
D
D
Boscaro
M
M
Fallo
F
F
D000311:Adrenal Glands / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000805:Angiotensin III / Q000378:metabolism*; D004077:Digoxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000378:metabolism*
D000804:Angiotensin II; D000805:Angiotensin III; D000450:Aldosterone; D004077:Digoxin; D012083:Renin