Dexamethasone does not inhibit antidiuretic hormone-stimulated prostaglandin production in vivo.
Glucocorticoids are potent inhibitors of prostaglandin (PG) release in vitro, but they fail to influence basal PG production in vivo. To test one possible explanation for this apparent discrepancy in the present study we investigated the effect of dexamethasone (DEX) on basal and antidiuretic hormone-stimulated renal PG synthesis in vivo. In long term experiments, Brattleboro diabetes insipidus rats were treated with DEX (250 micrograms kg-1 day-1) for 7 days, and the effects of deamino-8-D-arginine vasopressin were investigated on the fifth day of DEX treatment. Administration of deamino-8-D-arginine vasopressin was accompanied by a marked increase in PGE2 and PGF2 alpha excretion in both control and DEX-treated animals, but the response was significantly higher during DEX treatment. Furthermore, DEX, by itself, caused a significant increase in the excretion of both PGs. In short term experiments, diabetes insipidus rats received a 24-h iv infusion of DEX (1 mg kg-1 day-1), then renal PG synthesis was stimulated acutely by the infusion of arginine vasopressin (AVP) for 40 min. DEX treatment failed to inhibit basal PG excretion, and the AVP-induced enhancement of PGE2 and PGF2 alpha production was also identical in control and DEX-treated animals. DEX was ineffective in altering the hydroosmotic effect of AVP, confirming that intrarenal PG synthesis was not inhibited. We conclude that glucocorticoids in vivo do not inhibit anti-diuretic hormone-stimulated PG production, and thus, a differential effect of glucocorticoids on basal vs. stimulated PG synthesis cannot account for the discrepancy between in vivo and in vitro studies.
Náray-Fejes-Tóth
A
A
Fejes-Tóth
G
G
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000652:urine; D011460:Prostaglandins F / Q000652:urine; D051381:Rats; D011910:Rats, Brattleboro; D013997:Time Factors
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D001127:Arginine Vasopressin; D003907:Dexamethasone; D015237:Dinoprost; D015232:Dinoprostone