The role of corticosterone in corticotrophin (ACTH)-induced hypertension in the rat.
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
Mangos
G J
GJ
Department of Medicine, The St George Hospital, University of New South Wales, Kogarah, Australia. g.mangos@unsw.edu.au
Turner
S W
SW
Fraser
T B
TB
Whitworth
J A
JA
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014554:Urination / Q000187:drug effects
D009566:Nitrates; D009573:Nitrites; D019335:Nitroarginine; D000324:Adrenocorticotropic Hormone; D001120:Arginine; D003345:Corticosterone