Dexamethasone hypertension in rats: role of prostaglandins and pressor sensitivity to norepinephrine.
Glucocorticoid hypertension was induced by oral administration of dexamethasone (DX) in male Wistar rats. The mechanism of hypertension was studied by observing the changes in plasma renin activity, urinary excretion of prostaglandin E2 (PGE2), and the pressor response to norepinephrine. Following administration of DX (0.1 mg/day), the blood pressure began to rise within 3 days and reached a plateau on the 5th day (from 108 +/- 2 to 162 +/- 7 mm Hg, mean +/- SE). On the other hand, urine volume and urinary excretion of sodium were increased. In spite of the marked natriuresis and diuresis, the administration of DX resulted in a marked decrease in the urinary excretion of PGE2. This decrease in PGE2 excretion appeared before the blood pressure rose and continued throughout the experiment. Plasma renin activity did not change. The pressor response to norepinephrine was enhanced on the 2nd day of DX treatment, at which time the blood pressure was not yet elevated, and it was further augumented on the 6th day. In the DX-treated rats, the pressor response to norepinephrine was not enhanced by administration of indomethacin, whereas the pressor response was significantly potentiated by indomethacin in control rats. These results suggest that DX-induced hypertension in rats is associated with inhibition of prostaglandin synthesis leading to increased sensitivity in the vascular response to norepinephrine.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003907:Dexamethasone; D015232:Dinoprostone; D004231:Diuresis; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009318:Natriuresis; D009638:Norepinephrine / Q000494:pharmacology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011458:Prostaglandins E; D003907:Dexamethasone; D012083:Renin; D015232:Dinoprostone; D009638:Norepinephrine; D007213:Indomethacin