AJP - Renal Physiology, Vol 251, Issue 5 810-F816, Copyright © 1986 by American Physiological Society
Effects of gluco- and antiglucocorticoids on renal and aortic prostaglandin synthesis
J. P. Grunfeld, L. Eloy, A. Araujo and F. Russo-Marie
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.
