Investigation of effects of epoxygenases on the nanc relaxant responses induced by electrical field stimulation in rabbit corpus cavernosum

This aim of this study was to investigate the contributions of non-specific cytochrome P450 epoxygenase inhibitor, miconazole; specific ?-hydroxylase inhibitor, 17-ODYA; the metabolites of arachidonic acid, 14,15-EET, 11,12-EET ve 20-HETE epoxides on EFS mediated NO-dependent and -independent NANC relaxation responses in isolated rabbit corpus cavernosum. Isolated rabbit corpus cavernosum tissues which were obtained from male adult albino rabbits weighing 2,5-3 kg were suspended in organ bath chambers containing aerated Krebs solution to record isometric contractions via force displacement transducers. EFS mediated NANC relaxation responses were completely abolished by ?-conotoxin GVIA in the presence of guanethidine and atropine. However, L-NAME fully abolished EFS induced relaxation responses at the lower frequency (2 Hz), only reduced at higher frequencies (4-32 Hz). Miconazole and 17-ODYA increased both EFS induced NO-dependent and -independent NANC relaxation responses but there was no statistical significant difference between the groups. 14,15-EET, 11,12-EET ve 20-HETE also enhanced the NANC relaxation responses induced by EFS in both groups. There was no significant difference between 11,12-EET applied NO-dependent and -independent groups whereas in 14,15-EET applied NO-dependent relaxation responses were found to be increased insignificantly when compared to -independent. In 20-HETE applied NO-dependent group, statistical significant difference was observed at lower concentrations (10-11?10-8 M) when compared to -independent group. Cytochrome P450 mono-oxygenase inhibitors and epoxides didn?t produce relaxation response on NO-dependent and -independent groups pre-contracted tissues with phenylephrine.These results suggest that cytochrome P450 mono-oxygenase inhibitors and epoxides contribute to EFS mediated NO-dependent and -independent NANC relaxation responses and exert their effects by presynaptic mechanisms.