Cytochrome P-450-dependent vasodilation of rat kidney by arachidonic acid.
Our previous studies indicated a role for cytochrome P-450-dependent enzymes in generating the mediators of the vasodilator effect of arachidonic acid (AA) in the preconstricted indomethacin-treated perfused kidney of the rat. We report that in vivo induction of cytochrome P-450 enzymes with 3-methylcholanthrene-beta-naphthoflavone or dexamethasone enhanced the renal vasodilator effect of AA in this experimental preparation. Conversely, depletion of cytochrome P-450 enzymes with stannous chloride or cobalt chloride diminished the vasodilator response to AA. Injection of AA resulted in the release of relaxant material into the renal effluent detected by superfusion of rabbit aortic rings. Inhibition of cytochrome P-450 with 7-ethoxyresorufin reduced the release of vasorelaxant material. Metabolism of labeled AA by the kidney revealed four peaks of radioactivity that were recovered from the renal effluent. The heights of these peaks were reduced by 7-ethoxyresorufin. These results provide further evidence for cytochrome P-450-dependent metabolism of AA to one or more vasodilator products by the rat kidney.
Oyekan
A O
AO
Department of Pharmacology, New York Medical College, Valhalla 10595.
McGiff
J C
JC
Quilley
J
J
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001571:Benzoflavones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology / Q000502:physiology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*; D019324:beta-Naphthoflavone
D001095:Arachidonic Acids; D001571:Benzoflavones; D010656:Phenylephrine; D016718:Arachidonic Acid; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D007213:Indomethacin