The role of corticosterone in corticotrophin (ACTH)-induced hypertension in the rat

Objective Corticotrophin (ACTH)-induced hypertension in the rat is prevente d by L- but not D-arginine. We examined the effects of exogenous corticoste rone in the male Sprague Dawley (SD) rat to determine whether ACTH-induced hypertension is mediated by corticosterone, Methods Exogenous corticosterone (10, 20 or 40 mg/kg per day) or sham (poly ethylene glycol (PEG) 1 ml/kg per day) was injected subcutaneously in divid ed doses (s/c b.d.) over 15 treatment days to 40 SD rats (n = 10 each group ). Subsequently, the effects of L-arginine, D-arginine or L-arginine + N-ni tro-L-arginine (NOLA) on corticosterone-induced hypertension (corticosteron e 20 mg/kg per day) were examined. Systolic blood pressure (SBP) and metabo lic parameters were measured every two days. Results Twenty and 40 mg/kg per day of corticosterone increased SEP compare d with sham (P < 0.01, P < 0.05 respectively, sham versus respective group) . Forty mg/kg per day of corticosterone raised serum corticosterone concent ration compared with sham (502 +/- 20 versus 364 +/- 25 ng/ml, P < 0.001). L-arginine prevented the rise in SEP produced by corticosterone (131 +/- 3 to 131 +/- 2 mmHg, control versus day 10) but D-arginine did not (129 +/- 3 to 142 +/- 4 mmHg on day 8, P < 0.01). NOLA blocked the effect of L-argini ne and amplified the rise in blood pressure produced by corticosterone (130 +/- 3 to 171 +/- 6 mmHg on day 10, P < 0.001). Conclusions The haemodynamic features of ACTH-induced hypertension were rep roduced by corticosterone excess, at concentrations of corticosterone simil ar to those in studies of exogenous ACTH administration. It is likely that ACTH-stimulated adrenal production of corticosterone accounts for the featu res of ACTH-induced hypertension in the rat (C) 2000 Lippincott Williams & Wilkins.