POSSIBLE CONTRIBUTION OF PLATELET CYCLOOXYGENASE TO THE RENAL VASCULAR ACTION OF 5,6-EPOXYEICOSATRIENOIC ACID

5,6-Epoxyeicosatrienoic acid (5,6-EET), a cytochrome P450-dependent ar achidonate product, is a substrate for cyclooxygenase (COX) and, in so me vascular preparations, elicits COX-dependent vasodilation. In the b lood perfused rat kidney, 5,6-EET causes COX-dependent renal vasoconst riction, whereas in the rat isolated kidney perfused with a physiologi cal buffer, 5,6-EET produces dose-dependent vasodilation that is unaff ected by indomethacin. We examined the possible contribution of platel et COX to the vasoconstrictor action of 5,6-EET. Incubation of labeled 5,6-EET with rat washed platelets yields additional products that elu te between 14 to 17 min on high-performance liquid chromatography (HPL C) and cause constriction of the perfused kidney. Indomethacin decreas ed the formation of these products and reduced the vasoconstrictor cap acity of the corresponding HPLC fractions. Thus, platelet COX can meta bolize 5,6-EET to vasoconstrictor products that may contribute to the in vivo vasoconstrictor effect of this eicosanoid,