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• W2036938051 abstract "This study examined the role of cytochrome P450 (CYP) metabolites of arachidonic acid (AA) to rat corporal smooth muscle tone. 11, 12-Epoxyeicosatrienoic acid (EET) (10− 11–10− 6 M) produced dose-dependent relaxation of rat (control; 10 weeks old) corpus cavernosum with a pD2 value of 8.8 ± 0.2 and a maximal relaxation of 80 ± 9%, whereas 20-hydroxyeicosatetraenoic (20-HETE) did not have an effect. EET-mediated relaxation of corpus cavernosum was attenuated by 71 ± 3%, 55 ± 2%, 53 ± 5% and 84 ± 3% in the presence of nitro-l-arginine methyl ester (l-NAME) (10− 4 M), an inhibitor of nitric oxide (NO) synthase, iberiotoxin (5 × 10− 8 M), an inhibitor of calcium-activated potassium (BK) channels, glibenclamide (10− 5 M), an inhibitor of ATP-sensitive K+ channels or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10− 5 M), an inhibitor of soluble guanylyl cyclase, respectively. EET-mediated relaxation of rat corpus cavernosum was significantly less in the streptozotocin (STZ)-treated (diabetic) and 30 weeks old (older) animals compared to control. Carbachol (10− 9–10− 4 M)-induced relaxation was significantly reduced whereas phenylephrine (PE) (10− 9–5 × 10− 3 M)-induced contraction was significantly increased in the cavernosum strips from old and diabetic rats compared to the control. Pre-incubation of the cavernosum strips obtained from control, older or diabetic rats with N-hydroxy-N′-(4-butyl-2-methyl-phenyl)-formamidine (HET0016), a selective inhibitor of 20-HETE synthesis, or 1-cyclohexyl-3-dodecyl urea (CDU), a specific inhibitor of soluble epoxide hydrolase (sEH) resulted in a significant attenuation of PE-induced contraction and improvement in carbachol-induced relaxation. We conclude that 11, 12-EET-induced relaxation of the rat corpus cavernosum involves activation of cGMP/NO pathway as well as activation of ATP-sensitive K+ channels and BK channels. These results also suggest that inhibition of 20-HETE production or reduction of EET inactivation may have therapeutic potential to prevent erectile dysfunction associated with diabetes and aging." @default.
• W2036938051 created "2016-06-24" @default.
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• W2036938051 date "2007-11-01" @default.
• W2036938051 modified "2023-09-25" @default.
• W2036938051 title "Role of cytochrome P450 metabolites of arachidonic acid in regulation of corporal smooth muscle tone in diabetic and older rats" @default.
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• W2036938051 doi "https://doi.org/10.1016/j.vph.2007.08.002" @default.
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