Prostaglandin I2 and glucocorticoid-induced rise in arterial pressure in the rat.
The mechanism of glucocorticoid-induced hypertension is not known. Although glucocorticoids can exert an inhibitory effect on prostaglandin synthesis in vitro, their in vivo influence on this system is controversial. The goal of the present study was to determine whether dexamethasone-induced hypertension in Wistar rats is due to inhibition of the synthesis of the vasodilator prostaglandin I2 (PGI2) in vivo. Dexamethasone caused a profound reduction (7 +/- 1 versus 21 +/- 5 ng per 24 h) in the urinary excretion of PGI-M (PGI-M), a major metabolite of PGI2, and a sustained rise in systolic arterial pressure which was maximal after 5 days (144 +/- 9 versus 103 +/- 3 mmHg). A study of the metabolism of [3H]-labeled 6-oxo-PGF1 alpha and PGI2 revealed that dexamethasone exerted a dual action on the prostaglandin system in vivo: an inhibition of PGI2 biosynthesis and an alteration of its metabolism, both effects contributing to the observed reduction in urinary levels of PGI-M. Exogenous arachidonic acid induced a fourfold increase in urinary PGI-M in normal rats (from 14 +/- 3 to 61 +/- 6 ng per 24 h). Despite a large decrease upon addition of dexamethasone, urinary PGI-M remained in the high-normal range in arachidonic acid-treated rats (21 +/- 8 ng per 24 h). Arachidonic acid exerted antihypertensive effects which were marginal initially but significant in the later phase of dexamethasone-induced hypertension (124 +/- 8 versus 139 +/- 8 mmHg in arachidonic acid-treated versus control rats after 7 days of dexamethasone).(ABSTRACT TRUNCATED AT 250 WORDS)
Falardeau
P
P
Laboratory on Prostaglandins, Clinical Research Institute of Montreal, Quebec, Canada.
Martineau
A
A
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D008469:Meclofenamic Acid / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D008469:Meclofenamic Acid; D003907:Dexamethasone; D011464:Epoprostenol