Plasma concentrations, renal excretion, and tissue release of prostaglandins in the rat with dexamethasone-induced hypertension.
This study was designed to investigate whether the hypertension produced by dexamethasone in the rat is associated with a deficit in circulating and renal prostaglandin E2 (PGE2) and PGI2, PGs that are presumed to contribute to antihypertensive mechanisms. The administration of dexamethasone (2.5 mg kg-1 week-1, sc) increased systolic blood pressure by 41 +/- 6 mm Hg (P less than 0.05) after 14 days of treatment, associated with elevations of urine volume and fluid intake and loss of body weight. The glucocorticoid, however, had no effect on the plasma concentration, urinary excretion, or vascular and renal tissue release of immunoreactive 6-keto-PGF1 alpha, a PGI2 metabolite. In contrast, dexamethasone increased (P less than 0.05) the plasma PGE2 concentration by 157% and PGE2 urinary excretion by 134% after 14 days of treatment. However, the basal release of immunoreactive PGE2 as well as the angiotension II-induced release of radiolabeled arachidonic acid and PGs from renal medulla slices incubated in Krebs solution were diminished in rats receiving dexamethasone. The steroid also reduced to about 60% (P less than 0.05) of the control value the activity in renal homogenates of 15-hydroxyprostaglandin dehydrogenase (PGDH), a major PG-catabolizing enzyme, without affecting the activity of the enzyme in the lung. Hence, the increased plasma concentration and renal excretion of PGE2 caused by dexamethasone in the face of reduced renomedullary production of the PG is presumably related to diminished degradation in the kidney and perhaps in other extrapulmonary tissues. Altogether, this study demonstrates that the hypertension induced by dexamethasone in the rat is not associated with a deficit in circulating and renal PGE2 and PGI2.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000633:toxicity*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000652:urine; D011453:Prostaglandins / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine
D001095:Arachidonic Acids; D011453:Prostaglandins; D000804:Angiotensin II; D016718:Arachidonic Acid; D003907:Dexamethasone; D012964:Sodium; D011188:Potassium