Reciprocal effects of dexamethasone on vasodilatory responses to arachidonic acid and prostanoids in the isolated perfused rabbit kidney.
We reported that dexamethasone treatment of rabbits causes a reduction in renal vasoconstrictor responses to prostaglandin F2 alpha and U46619, an agonist at the thromboxane-endoperoxide receptor, but not to phenylephrine. The purpose of this study was to examine if dexamethasone treatment can affect the renal vasodilatory responses to prostacyclin (PGI2) and prostaglandin E2 (PGE2) in isolated Krebs-perfused kidneys constricted with phenylephrine. In kidneys from dexamethasone-treated rabbits, the vasodilatory response to PGI2 was reduced by 57%, whereas that to PGE2 was converted to a vasoconstrictor response. This effect of dexamethasone appears to be specific in that the renal vasodilatory responses to forskolin and to sodium nitroprusside were not affected by the steroid. Contrasting with the inhibitory effect of dexamethasone on prostanoid-induced renal vasodilation, treatment with dexamethasone augmented the renal vasodilatory response to arachidonic acid; for example, arachidonic acid, at 10 micrograms decreased perfusion pressure by 24.8 +/- 5.4 and 49.0 +/- 5.6 mm Hg in kidneys from vehicle- and dexamethasone-treated rabbits, respectively. The enhanced vasodilatory effect of arachidonic acid could not be attributed to increased renal formation of PGE2 and PGI2. In conclusion, dexamethasone interferes with prostanoid-mediated renal vasodilation, which is not associated with an impairment in renal responsiveness to direct activators of adenylate cyclase and guanylate cyclase. The reciprocal effect of dexamethasone on the renal vascular responses to arachidonic acid and vasodilatory prostanoids are indicative of a previously unrecognized influence of glucocorticoids on the renal arachidonate-prostaglandin system.
Sessa
W C
WC
Department of Pharmacology, New York Medical College, Valhalla 10595.
Lin
L
L
Nasjletti
A
A
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D011312:Pressure; D011453:Prostaglandins / Q000494:pharmacology*; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects*; D014664:Vasodilation
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D003907:Dexamethasone; D015232:Dinoprostone