Methylprednisolone-induced hypertension in the rat: evidence against the role of plasma volume changes, vasopressin and renal prostaglandin E2.
The purpose of the study was to clarify the mechanism(s) of glucocorticoid-induced hypertension. Hypertension was induced in rats by single i.m. injection of methylprednisolone (MP) 20 mg/kg. In normal Wistar rats, systolic blood pressure (SBP) increased by 30 mmHg from days 2 to 10 after MP. Urinary sodium excretion increased transiently and sodium balance was negative. Plasma volume (PV; ml/100 g body weight) increased on day 5, but was unchanged on day 2 after MP, at a time when SBP had already increased. In rats with chronic renal failure (CRF) and low sodium intake, SBP increased more than in control rats (48 versus 22 mmHg on day 10). Hypertension was not accompanied by a significant drop in urinary excretion of prostaglandin E2 (PGE2; measured by radio-immunoassay). In normal MP-injected rats, PGE2 excretion decreased slightly and then increased; in CRF rats, basal PGE2 excretion was too low to evaluate the effect of MP. In homozygous Brattleboro rats lacking antidiuretic hormone (ADH), MP increased SBP by 28 mmHg (day 10). Similar changes were obtained in heterozygous Brattleboro rats. The changes in PV were identical to those found in Wistar rats. We conclude that increase in PV, change in PGE2 and vasopressin do not play a key role in MP hypertension. Direct effect of glucocorticoid on vascular receptors is likely to be involved in this model.
D000818:Animals; D001810:Blood Volume; D004039:Diet, Sodium-Restricted; D015232:Dinoprostone; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007668:Kidney / Q000502:physiology; D008297:Male; D008775:Methylprednisolone; D009392:Nephrectomy; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011910:Rats, Brattleboro; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000502:physiology
D011458:Prostaglandins E; D014667:Vasopressins; D015232:Dinoprostone; D008775:Methylprednisolone