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  • Title: The role of corticosterone in corticotrophin (ACTH)-induced hypertension in the rat.
    Author: Mangos GJ, Turner SW, Fraser TB, Whitworth JA.
    Journal: J Hypertens; 2000 Dec; 18(12):1849-55. PubMed ID: 11132610.
    Abstract:
    OBJECTIVE: Corticotrophin (ACTH)-induced hypertension in the rat is prevented by L- but not D-arginine. We examined the effects of exogenous corticosterone 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 (polyethylene glycol (PEG) 1 ml/kg per day) was injected subcutaneously in divided 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-nitro-L-arginine (NOLA) on corticosterone-induced hypertension (corticosterone 20 mg/kg per day) were examined. Systolic blood pressure (SBP) and metabolic parameters were measured every two days. RESULTS: Twenty and 40 mg/kg per day of corticosterone increased SBP compared with sham (P< 0.01, P< 0.05 respectively, sham versus respective group). Forty mg/kg per day of corticosterone raised serum corticosterone concentration compared with sham (502 +/- 20 versus 364 +/- 25 ng/ml, P < 0.001). L-arginine prevented the rise in SBP 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-arginine 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 reproduced by corticosterone excess, at concentrations of corticosterone similar to those in studies of exogenous ACTH administration. It is likely that ACTH-stimulated adrenal production of corticosterone accounts for the features of ACTH-induced hypertension in the rat
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