Effects of epoxygenases on the nonadrenergic noncholinergic relaxant responses induced by electrical field stimulation in rabbit corpus cavernosum

Abstract

We aimed to investigate the effects of epoxygenases on electrical field stimulation (EFS)-mediated nitric oxide (NO)-dependent and NO-independent nonadrenergic noncholinergic (NANC) relaxations in isolated rabbit corpus cavernosum. The tissues of 20 male adult albino rabbits (2.5-3 kg) were suspended in organ baths containing aerated Krebs solution, and isometric contractions were recorded. EFS-mediated NANC relaxations were obtained on phenylephrin (3 × 10 −5 M)-contracted tissues in the presence of guanethidine (10 −6 M) and atropine (10 −6 M). Miconazole (10 −9 -10 −4 M), 17-octadecynoic acid (ODYA) (10 −10 -10 −5 M), 14,15-epoxyeicosatrienoic acid (EET) (10 −11 -10 −8 M), 11,12-EET (10 −12 -3 × 10 −8 M) and 20-hydroxyeicosatetraenoic acid (HETE) (10 −11 -3 × 10 −8 M) were added cumulatively (n = 5-7 for each set of experiments). For NO-independent relaxations, N ω -nitro-l-arginine methyl ester (l-NAME) (10 −4 M) was added before a group of experiments. Depending on the concentration, miconazole, 17-ODYA, 14,15-EET, 11,12-EET, and 20-HETE significantly enhanced both NO-dependent and NO-independent EFS-mediated relaxations (p < 0.05). Epoxygenases showed similar effect on NO-dependent and NO-independent relaxant responses except 20-HETE which caused significantly more enhanced relaxation on NO-dependent responses (p < 0.05). No drug caused a significant relaxation response on tissues contracted with phenylephrine. Epoxygenases contribute to EFS-mediated NO-dependent and NO-independent NANC relaxations by presynaptic mechanisms, offering a new treatment alternative for erectile dysfunction which needs to be explored in further in vivo, molecular and clinical studies. K E Y W O R D S corpus cavernosum, electrical field stimulation, epoxygenase, isolated organ bath, nonadrenergic noncholinergic system 1 | INTRODUC TI ON Penile erection is a neurovascular event controlled by physiological factors and hormones (Martínez-Salamanca et al., 2010). Arousal of the pelvic plexus and the cavernosal nerves causes erection, and sympathetic nerves enable the penis to return to the flaccid state (Andersson, 2011). Erectile dysfunction (ED) is defined as the inability to achieve and continue to maintain penile erection. Nitric oxide (NO)-cyclic GMP