Dose-response relationships and mineralocorticoid activity in cortisol-induced hypertension in humans.
OBJECTIVE
This study was designed to define the dose-response relationships for cortisol-induced hypertension in humans and to test the hypothesis that cortisol-induced hypertension is a consequence of classical mineralocorticoid actions using the mineralocorticoid antagonist spironolactone.


METHODS
In study 1, six normal men were given cortisol orally every 6 h for 5 days at doses of 40, 80 and 200 mg per day. In study 2, six normal men were given spironolactone at 400 mg/day for 6 days and cortisol at 80 mg/day for 5 days, commencing on the second day of spironolactone treatment.


RESULTS
Systolic blood pressure increased significantly with cortisol at 80 and 200 but not 40 mg/day. There was no difference between 80 and 200 mg/day. Weight increases were seen at the two higher doses and serum potassium concentration fell with each dose. Spironolactone prevented the increase in body weight and the decrease in serum potassium but did not affect the increase in blood pressure produced by cortisol.


CONCLUSIONS
Cortisol at 80 and 200 mg per day produces similar blood pressure and metabolic effects. Spironolactone blocked the mineralocorticoid effects of cortisol but not the blood pressure rise, suggesting that these mineralocorticoid effects are not responsible for cortisol-induced hypertension.
Williamson
P M
PM
Department of Medicine, University of New South Wales, St George Hospital, Kogarah, New South Wales, Australia.
Kelly
J J
JJ
Whitworth
J A
JA
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology
D004573:Electrolytes; D008901:Mineralocorticoids; D013148:Spironolactone; D006854:Hydrocortisone