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• W2283724467 endingPage "R2141" @default.
• W2283724467 startingPage "R2132" @default.
• W2283724467 abstract "Endothelin-1 (ET-1) produces potent renal effects that we have previously shown to be dependent on cytochrome P-450 (CYP450) metabolites of aracidonic acid (24) This study evaluated the role of these metabolites in the effects produced by ET-1 on renal blood flow (RBF), cortical blood flow (CBF), medullary blood flow (MBF), and mean arterial blood pressure (MBP). ET-1 (20–200 pmol/kg) increased MBP, renal vascular resistance (RVR), and MBF but reduced CBF and RBF in a dose-dependent manner. The decreases in CBF and RBF, and increases in MBP and RVR were blunted by BMS-182874, an ET a receptor antagonist or BQ-788, an ET b receptor antagonist. Similarly, indomethacin, an inhibitor of cyclooxygenase activity, or 12,12-dibromododecenoic acid (DBDD), a CYP450-dependent inhibitor of production of 20-hydroxyeicosatetraenoic acid (20-HETE), blunted these effects. ET-3 elicited dose-related reduction in CBF and increase in MBF. Indomethacin accentuated the reduction in CBF and attenuated the increase in MBF, as did DBDD. ET-1-induced increase in MBF was attenuated by BQ-788, N ω -nitro-l-arginine methyl ester (l-NAME), an inhibitor of nitric oxide (NO) synthesis, indomethacin, or DBDD. DBDD inhibited the hemodynamic effects ofl-NAME. Miconazole, the inhibitor of CYP450-dependent epoxygenase activity, was without effect. These results indicate that hemodynamic changes produced by ET-1 are mediated by vasoconstrictor prostanoids and/or prostanoid-like substances, possibly, 20-HETE via activation of ET a and ET b receptors. However, the increase in MBF is mediated by vasodilator prostanoids or by NO via ET b receptor activation." @default.
• W2283724467 created "2016-06-24" @default.
• W2283724467 creator A5054387835 @default.
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• W2283724467 date "2000-12-01" @default.
• W2283724467 modified "2023-10-15" @default.
• W2283724467 title "Role of NO and cytochrome<i>P</i>-450-derived eicosanoids in ET-1-induced changes in intrarenal hemodynamics in rats" @default.
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• W2283724467 doi "https://doi.org/10.1152/ajpregu.2000.279.6.r2132" @default.
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