Adrenocorticotrophin-induced hypertension: effects of mineralocorticoid and glucocorticoid receptor antagonism

Objective To examine whether the increase of blood pressure in adrenocortic otrophin-treated rats is mediated through mineralocorticoid or glucocortico id receptors or corticosterone 6 beta-hydroxylation inhibition. Design Rats were randomly allocated to 14 treatment groups for 10 days. The treatments included sham injection (n = 35), adrenocorticotrophin (5, 100, 500 mu g/kg per day, subcutaneously, n = 5, 15 and 15, respectively), spir onolactone (100 mg/kg per day, subcutaneously, n = 15), standard-dose or hi gh-dose RU 486 (70 mg/kg every 3 days or 70 mg/kg per day, subcutaneously, n = 5 and 10, respectively), spironolactone + adrenocorticotrophin (100 mu g/kg per day, n = 5, or 500 mu g/kg per day, n = 10), standard-dose RU 486 + adrenocorticotrophin (500 mu g/kg per day, n = 5), high-dose RU 486 + adr enocorticotrophin (100 mu g/kg per day, n = 10), troleandomycin (40 mg/kg p er day, subcutaneously, n = 5) and troleandomycin + adrenocorticotrophin (5 mu g/kg per day, n = 5). Systolic blood pressure and metabolic parameters were measured every second day. Results Adrenocorticotrophin treatment increased systolic blood pressure do se-dependently (5 mu g/kg per day: +14 +/- 2 mmHg; 100 mu g/kg per day: +20 +/- 2 mmHg; 500 mu g/kg per day: +28 +/- 2 mmHg, all P < 0.001). Adrenocor ticotrophin at 100 and 500 mu g/kg per day increased plasma sodium and decr eased plasma potassium concentrations. Spironolactone did not block adrenoc orticotrophin-induced systolic blood pressure changes but did block changes in plasma sodium and potassium levels. Standard-dose RU 486 did not modify the adrenocorticotrophin-induced (500 mu g/kg per day) systolic blood pres sure rise but blocked the effect of adrenocorticotrophin on body weight Hig h-dose RU 486 partially blocked the adrenocorticotrophin-induced (100 mu g/ kg per day) systolic blood pressure increase (adrenocorticotrophin at 100 m u g/kg per day: 143 +/- 3 mmHg; high-dose RU 486 + adrenocorticotrophin at 100 mu g/kg per day: 128 +/- 5 mmHg, P < 0.001) and body-weight loss. Trole andomycin did not alter the development of adrenocorticotrophin-induced hyp ertension. Conclusions Spironolactone and standard-dose RU 486 did not modify adrenoco rticotrophin-induced hypertension despite demonstrable antimineralocorticoi d and antiglucocorticoid actions. High-dose RU 486 partially blocked adreno corticotrophin-induced (100 mu g/kg per day) hypertension, suggesting eithe r a permissive effect of glucocorticoid on blood pressure or other antihype rtensive actions of RU 486. Inhibition of glucocorticoid 6 beta-hydroxylati on by troleandomycin did not modify adrenocorticotrophin-induced hypertensi on, suggesting that effects of corticosterone 6 beta-hydroxylation in adren ocorticotrophin-induced hypertension are negligible. J Hypertens 1999, 17:4 19-426 (C) Lippincott Williams & Wilkins.