Nitric oxide-epoxygenase interactions and arachidonate-induced dilation of rat renal microvessels

Oyekan. Nitric oxide-epoxygenase interactions and arachidonate-induced dilation of rat renal microvessels. Am J Physiol Heart Circ Physiol 285: H2054‐H2063, 2003. First published July 24, 2003; 10.1152/ajpheart.00075.2003.—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, 0.03‐1 M) or bradykinin (BK, 0.1‐3 M) elicited NO- and prostanoid-independent vasodilation. Miconazole (1.5 M) or 6-(2-propargyloxyphenyl)hexanoic acid (30 M), 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 M) inhibited these responses. Apamin (1 M), which is a largeconductance Ca 2 -activated K (BKCa) channel inhibitor, or 18-glycyrrhetinic acid (30 M), which is an inhibitor of myoendothelial gap junctional electromechanical coupling, also inhibited these responses. NO donors spermine NONOate (1 and 3 M) or sodium nitroprusside (0.3 and 3 M) but not 8-bromo-cGMP (100 M), which is an analog of cGMP (the second messenger of NO), blunted the dilation produced