Adrenocorticotropin and cortisol-induced changes in urinary sodium and potassium excretion in man: effects of spironolactone and RU486.
The role of the glucocorticoid (type II) receptor in the Na+ retention induced by cortisol is not known. The relative contribution of mineralocorticoid (type I) and type II receptor activation to changes in urinary Na+ and K+ excretion in man was studied using spironolactone and RU486 to inhibit type I and II receptors, respectively. Normal men eating a constant daily diet received either ACTH or cortisol for 5 days. Spironolactone (400 mg/day) inhibited ACTH (80 U/day)-induced kaliuresis, but not the Na+ retention produced by ACTH or cortisol (240 mg/day) and only blunted the modest Na+ retention induced by cortisol (120 mg/day). RU486 (1200 mg/day for the first 2 day) inhibited the first day kaliuresis and carbohydrate intolerance produced by cortisol, but did not affect the Na+ retention. Thus, the kaliuresis produced by cortisol and ACTH can be attributed to type II and type I receptor activation, respectively. The failure of RU486 to inhibit the Na+ retention induced by cortisol with evidence of adequate blockade of type II receptors indicates that the Na+ retention produced by cortisol is not mediated by type II receptor activation, but is, at least in part, mediated by the type I receptor.
Clore
J N
JN
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Estep
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Ross-Clunis
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Watlington
C O
CO
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002712:Chlorides / Q000652:urine; D004963:Estrenes / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D015735:Mifepristone; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000652:urine*; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000187:drug effects; D013148:Spironolactone / Q000494:pharmacology*
D001786:Blood Glucose; D002712:Chlorides; D004963:Estrenes; D007328:Insulin; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D013148:Spironolactone; D015735:Mifepristone; D000324:Adrenocorticotropic Hormone; D011188:Potassium; D006854:Hydrocortisone