Adrenocorticotrophin-induced hypertension in rats. Role of progesterone and digoxin-like substances.
Adrenocorticotrophin (ACTH) administration raises blood pressure in humans, sheep, and the rat. ACTH hypertension can be reproduced in sheep by combined infusion of aldosterone, 17 alpha-OH-progesterone, and 17 alpha,20 alpha-OH-progesterone, and in humans by cortisol. In the rat, ACTH hypertension is probably due to corticosterone. Progesterone treatment can prevent ACTH-induced hypertension in sheep. This study examined the ability of progesterone to antagonize the onset and development of ACTH-induced hypertension in Sprague-Dawley rats (n = 44). We also investigated the relationship of plasma digoxin-like substances (DLS) to ACTH hypertension. ACTH (0.5 mg/kg/day) significantly increased blood pressure (+24 +/- 5 mm Hg, P < .001) in association with an increase of water intake, urine output, and plasma sodium concentration, and a decrease of body weight and plasma potassium concentration. ACTH increased plasma DLS (+132 +/- 18 pg/mL, P < .01), and there was a positive correlation between DLS and blood pressure (r = 0.68, n = 22, P < .001). Progesterone (50 mg/kg/day) did not block the development of ACTH-induced hypertension in the rat. Although progesterone prevented the ACTH-induced rise in plasma sodium and glucose concentration, it did not prevent the decrease in plasma potassium concentration. The failure of progesterone to prevent ACTH-induced hypertension in the rat argues against a common "hypertensinogenic" mechanism for ACTH hypertension in sheep and rat. DLS may play a role in ACTH-induced hypertension in the rat.
Li
M
M
Department of Medicine, St. George Hospital, Kogarah, Australia.
Wong
K S
KS
Martin
A
A
Whitworth
J A
JA
D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004077:Digoxin / Q000097:blood / Q000378:metabolism*; D004326:Drinking / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011188:Potassium / Q000097:blood / Q000652:urine; D011374:Progesterone / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood / Q000652:urine
D001786:Blood Glucose; D011374:Progesterone; D004077:Digoxin; D000324:Adrenocorticotropic Hormone; D012964:Sodium; D011188:Potassium