Effects of gluco- and antiglucocorticoids on renal and aortic prostaglandin synthesis.
The effects of glucocorticoid agonists RU 26988 (G) and dexamethasone (D) and antagonist RU 486 (AG) on aortic and renal prostaglandin (PG) production were studied in Wistar rats. Blood pressure increased in rats administered G (20 mg X kg-1 X day-1) during 1 or 3 days; such increase was prevented by AG (100 mg X kg-1 X day-1). Renal papillary PGE2 release was increased after a 3-day administration of G, and this was prevented by AG. Neither G nor AG altered basal 6-keto-PGF1 alpha aortic production. However, G inhibited and AG magnified the stimulatory effect of ionophore A 23187, added in vitro, on 6-keto-PGF1 alpha production; AG reversed G inhibition. In addition, AG alone (20 mg X kg-1 X day-1 X 3 days) enhanced the stimulatory effect of angiotensin II (10(-8) M), added in vitro, on 6-keto-PGF1 alpha release. In vitro studies were performed on renomedullary interstitial cells grown in culture; G and D depressed PGE2 production in a dose-dependent manner; AG at equimolar 10(-8) M concentration inhibited this effect. In conclusion, AG inhibits the effects of G on blood pressure and PG synthesis. G exerts strong depressor activity on in vitro PGE2 renal production, whereas in vivo effects are more complex. Endogenous G inhibits aortic prostacyclin production, an action unmasked by AG administration. Diminished stimulation of vascular prostacyclin synthesis may contribute to vascular hyperreactivity in G-induced hypertension.
D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000502:physiology*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D015735:Mifepristone; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000732:Androstanols; D004963:Estrenes; D005938:Glucocorticoids; D011453:Prostaglandins; D015735:Mifepristone; D000001:Calcimycin; C038341:RU 26988; D003907:Dexamethasone