{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T22:35:35Z","timestamp":1771626935032,"version":"3.50.1"},"reference-count":41,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:p>Nitric oxide (NO) is an inhibitor of hemoproteins including cytochrome P-450 enzymes. This study tested the hypothesis that NO inhibits cytochrome P-450 epoxygenase-dependent vascular responses in kidneys. In rat renal pressurized microvessels, arachidonic acid (AA, 0.03\u20131 \u03bcM) or bradykinin (BK, 0.1\u20133 \u03bcM) elicited NO- and prostanoid-independent vasodilation. Miconazole (1.5 \u03bcM) or 6-(2-propargyloxyphenyl)hexanoic acid (30 \u03bcM), both of which are inhibitors of epoxygenase enzymes, or the fixing of epoxide levels with 11,12-epoxyeicosatrienoic acid (11,12-EET; 1 and 3 \u03bcM) inhibited these responses. Apamin (1 \u03bcM), which is a large-conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>(BK<jats:sub>Ca<\/jats:sub>) channel inhibitor, or 18\u03b1-glycyrrhetinic acid (30 \u03bcM), which is an inhibitor of myoendothelial gap junctional electromechanical coupling, also inhibited these responses. NO donors spermine NONOate (1 and 3 \u03bcM) or sodium nitroprusside (0.3 and 3 \u03bcM) but not 8-bromo-cGMP (100 \u03bcM), which is an analog of cGMP (the second messenger of NO), blunted the dilation produced by AA or BK in a reversible manner without affecting that produced by hydralazine. However, the non-NO donor hydralazine did not affect the dilatory effect of AA or BK. Spermine NONOate did not affect the dilation produced by 11,12-EET, NS-1619 (a BK<jats:sub>Ca<\/jats:sub>channel opener), or cromakalim (an ATP-sensitive K<jats:sup>+<\/jats:sup>channel opener). AA and BK stimulated EET production, whereas hydralazine had no effect. On the other hand, spermine NONOate (3 \u03bcM) attenuated basal (19 \u00b1 7%; P &lt; 0.05) and AA stimulation (1 \u03bcM, 29 \u00b1 9%; P &lt; 0.05) of renal preglomerular vascular production of all regioisomeric EETs: 5,6-; 8,9-; 11,12-; and 14,15-EET. These results suggest that NO directly and reversibly inhibits epoxygenase-dependent dilation of rat renal microvessels without affecting the actions of epoxides on K<jats:sup>+<\/jats:sup>channels.<\/jats:p>","DOI":"10.1152\/ajpheart.00075.2003","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:13:37Z","timestamp":1425413617000},"page":"H2054-H2063","source":"Crossref","is-referenced-by-count":28,"title":["Nitric oxide-epoxygenase interactions and arachidonate-induced dilation of rat renal microvessels"],"prefix":"10.1152","volume":"285","author":[{"given":"I. T.","family":"Udosen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. C.","family":"Hercule","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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