The role of corticosterone in corticotrophin (ACTH)‐induced hypertension in the rat
作者:
George Mangos,
Steven Turner,
Tafline Fraser,
Judith Whitworth,
期刊:
Journal of Hypertension
(OVID Available online 2000)
卷期:
Volume 18,
issue 12
页码: 1849-1855
ISSN:0263-6352
年代: 2000
出版商: OVID
关键词: hypertension;glucocorticoid;corticosterone;rat;N-nitro-L-arginine;L-arginine
数据来源: OVID
摘要:
ObjectiveCorticotrophin (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.MethodsExogenous 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.ResultsTwenty 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 orticosterone (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).ConclusionsThe 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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