Ismail Mert Vural

Effects of Varicocele on Electrical Field Stimulation-Induced Biphasic Twitch Responses in the Ipsilateral and Contralateral Rat Vasa Deferentia

Aim: Although little is known about the mechanisms, varicocele is considered as one of the factors leading to male infertility. Since reduced motility of the vas deferens was shown to contribute to male infertility, in this study we aimed to investigate the effect of varicocele on electrical field stimulation (EFS)-induced biphasic contractions of the vas deferens in order to evaluate the effect of varicocele on the motility of the vas deferens. Material and Methods: A total of 26 Sprague-Dawley rats (200–250 g) were assigned randomly into two groups: sham (n = 10) and varicocele (n = 16). Varicocele was produced by partial obstruction of the left renal vein. Four weeks after the surgical procedure, vasa deferentia were harvested and EFS-induced responses were recorded from the strips prepared from ipsilateral and contralateral sides via Grass isometric force displacement transducers. Exogenous α-β methyl ATP was applied at the concentration of 10–5M to the vasa deferentia strips, and exogenous noradrenalin was applied cumulatively at the concentrations between 10–7 and 10–4M. At the end of each experiment, 80 mM KCl was applied to induce contractions. All contractions were expressed as the percentage of the 80 mM KCl-induced contractions. Results: Varicocele significantly inhibited both phases of EFS-induced biphasic contractions in the ipsilateral side, whereas in the contralateral site it did not produce any change. However, there was no change in exogenously applied α-β methyl ATP, noradrenalin and KCl-evoked contractions of the vasa deferentia obtained from both sides. Conclusions: These results suggest that varicocele affects the ipsilateral vas deferens motility by reducing neurotransmitter release.

Enhancement effects of nicotine on neurogenic relaxation responses in the corpus cavernosum in rabbits: the role of nicotinic acetylcholine receptor subtypes.

Nicotine acts as an agonist of nicotinic acetylcholine receptors, which belong to a superfamily of neurotransmitter-gated ion channels. We previously demonstrated that nicotine increases the electrical field stimulation (EFS)-evoked nitrergic relaxation responses via activation of nicotinic acetylcholine receptors. The aim of the present study is to investigate the subtypes of nicotinic acetylcholine receptors in rabbit corpus cavernosum. EFS-evoked relaxation responses were recorded from corpus cavernosum strips obtained from rabbits with an isometric force displacement transducers. Effects of nicotine on EFS-evoked relaxations were examined in pre-contracted tissues. Then the effect of nicotine on the EFS-evoked relaxations was examined in the presence of hexamethonium, dihydro-beta-erythroidine, mecamylamine or alpha-bungarotoxin. In our study, nicotine (3 x 10(-5), 10(-4)) transiently increased nitrergic relaxations induced by EFS in the rabbit isolated corpus cavernosum. While hexamethonium and mecamylamine near totally inhibited or abolished the neurorelaxation response to nicotine (3 x 10(-5)) on EFS, dihydro-beta-erythroidine and alpha-bungarotoxin partially inhibited these responses. These findings demonstrated that the alpha3-beta4, alpha4-beta2 and alpha7 subunits of nicotinic acetylcholine receptors play role on the nicotine-induced augmentation in EFS-evoked relaxation responses in rabbit corpus cavernosum.

Functional Characterization of Nonadrenergic Noncholinergic Neurotransmitter Release via Endocannabinoids: An in Vitro Study in Rabbit Corpus Cavernosum

INTRODUCTION Corporal smooth muscle relaxation is mediated mainly but not completely by nitric oxide. Endocannabinoids modulate the various neurotransmitter systems. AIM In the present study, a possible role of endocannabinoids on non-nitrergic nonadrenergic noncholinergic (NANC)-mediated relaxations was investigated. METHODS In precontracted tissues, control electrical field stimulation (EFS)-induced NANC relaxation responses were obtained using varying frequencies of stimulation in the presence of L-arginine methyl ester (L-NAME), guanethidine, and atropine. To investigate the effects of cannabinoids on EFS-evoked non-nitrergic NANC relaxation responses, a similar experimental procedure was applied in the presence of cannabinoid receptor antagonists AM251 or AM630; vanilloid receptor antagonist capsazepine; or cannabinoid receptor agonists anandamide, arachidonyl-2-chloroethylamide (ACEA), or JHW015. MAIN OUTCOME MEASURES Effects of cannabinoid receptor antagonists and agonists on EFS-evoked non-nitrergic NANC relaxation responses. RESULTS L-NAME abolished EFS-induced relaxation responses at lower frequencies (2-4 Hz) and inhibited the relaxation responses at higher frequencies (8-32 Hz). AM251 and AM630 either together or separately inhibited, whereas anandamide, ACEA, and JHW015 enhanced non-nitrergic NANC relaxation responses. Anandamide did not alter EFS-induced non-nitrergic NANC relaxations in the presence of AM251 and AM630. Capsazepine enhanced non-nitrergic NANC relaxation responses. CONCLUSION These results suggest that non-nitrergic NANC relaxations may be mediated partially by cannabinoid-like neuronal factors acting at both cannabinoid CB(1) and cannabinoid CB(2) receptors.

Role of nicotinic acetylcholine receptor subtypes on nicotine-induced neurogenic contractile response alternation in the rabbit gastric fundus

Nicotine is a nonspecific agonist of nicotinic acetylcholine receptors. We previously demonstrated that nicotine increases the electrical field stimulation (EFS)-evoked contractile responses possibly by facilitating neurotransmitters release from nerve terminals by a mechanism dependent on the influx of Ca(2+) from voltage gated Ca(2+) channels via activation of nicotinic acetylcholine receptor. The aim of this study is to investigate subtypes of presynaptic nicotinic acetylcholine receptors involved in nicotine induced EFS-evoked contractile response alternation in the rabbit gastric fundus. EFS-evoked contractile responses were recorded from gastric fundus strips obtained from rabbits with isometric force displacement transducers. Effects of nicotine on EFS evoked contractions were examined. Then the effect of nicotine on the EFS-evoked contractions was examined in the presence of hexamethonium, dihydro-beta-erythroidine, mecamylamine or alpha-bungarotoxin. In our study, nicotine (10(-4), 3x10(-4) M) transiently increased neurogenic contraction induced by EFS in the rabbit isolated gastric fundus. While hexamethonium, dihydro-beta-erythroidine and mecamylamine inhibited the neurocontractile response to nicotine on EFS, alpha-bungarotoxin did not alter these responses. The pA(2) values of the antagonists were 4.67 (hexamethonium, n=8), 5.33 (dihydro-beta-erythroidine, n=8) and 5.43 (mecamylamine, n=8). These findings showed that the alpha3beta4 and alpha4beta2 subunits of nicotinic acetylcholine receptors play a role on the nicotine-induced augmentation in EFS-evoked contractile responses in rabbit gastric fundus.

Investigation of myorelaxant activity of 9-aryl-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-diones in isolated rabbit gastric fundus

In this study, twelve compounds having 9-aryl-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione structure were synthesized by reaction of 5-methyl-1,3-cyclohexanedione, the appropriate aromatic aldehydes, and ammonium acetate in methanol. The structures of the compounds were elucidated by infrared, 1H- and 13C-nuclear magnetic resonance spectroscopy (-NMR), mass spectroscopy, and elemental analysis. The maximum relaxant effects (Emax) and pD2 values of the compounds 3a–l and pinacidil were tested on isolated strips of rabbit gastric fundus smooth muscle.

Hydrogen peroxide and antioxidizing enzymes involved in modulation of transient facilitatory effects of nicotine on neurogenic contractile responses in rat gastric fundus

Nicotine acts as an agonist of nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors play a role in the modulation of neurotransmitter release in both the central and the peripheral nervous system. Moderate reactive oxygen species levels modulate the regulation of physiological functions e.g. neurotransmitter release. Previously in rabbit gastric fundus we demonstrated that nicotine transiently increased neurogenic contraction induced by electrical field stimulation (EFS). In this study we aimed to investigate the effects of hydrogen peroxide (H2O2), antioxidizing enzymes catalase and superoxide dismutase (SOD) on nicotine induced increases at cholinergic neurotransmission in rabbit gastric fundus. Although H2O2 did not alter nicotine induced transient neurogenic contractions at concentrations of 10(-6) and 10(-5) M, at high concentration (10(-4) M) H2O2 inhibited nicotine induced increases. Catalase (500 units/ml), enhanced the effect of nicotine but did not alter nicotine induced transient neurogenic contractions at the concentrations of 100 and 250 units/ml. SOD (75,150 and 225 units/ml) did not alter nicotine induced transient neurogenic contractions. In conclusion, at high concentration H2O2 (10(-4) M) inhibited nicotines transient ability to augment neurogenic contractions and catalase (500 units/ml) enhanced the effect of nicotine.

Effects of Mexiletine on Electrical Field Stimulation-Induced Contractile Responses in the Ipsilateral and Contralateral Vasa Deferentia after Unilateral Testicular Torsion/Detorsion

Aim: To investigate testicular torsion-induced changes on the electrical field stimulation (EFS)-induced contractions in rabbit vasa deferentia and to evaluate the effect of mexiletine. Methods: 18 male New Zealand albino rabbits were used in this experiment. Rabbits were divided into three groups: (1) control group (n = 6); (2) torsion group (n = 6), and (3) mexiletine group (n = 6). In the control group, vasa deferentia on both sides were harvested. In the torsion and mexiletine groups, the left testes of the rabbits were subjected to 720° of clockwise torsion for 2 h and then detorsion was performed. In the mexiletine group, 50 mg/kg i.p. mexiletine was administered 1 h before detorsion. Following 24 h of the torsion, vasa deferentia on both sides were harvested and 2-cm strips including both the prostatic and epididymal portions were prepared to record EFS-induced contractions. Results: Testicular torsion caused a significant inhibition in both phases of EFS-induced biphasic contractions of the ipsi- and contralateral vasa deferentia. Mexiletine treatment did not affect these inhibitory responses. Torsion/detorsion of the spermatic cord did not alter exogenously applied noradrenaline-induced contractions in both vasa deferentia. However, KCl-induced contractions diminished significantly in ipsilateral vas deferens of the torsion group and mexiletine restored this inhibition. Conclusions: Unilateral testicular torsion/detorsion leads to inhibition in both phases of EFS-induced biphasic contractions of the ipsi- and contralateral vasa deferentia by causing a defect in presynaptic nerve transmission. However, mexiletine has no effect on this inhibition. Inhibition of the KCl-induced contractions in the ipsilateral vas deferens, which indicates postsynaptic tissue damage, is restored by administering mexiletine 1 h prior to detorsion.

EFFECTS OF CANNABINOID RECEPTOR ACTIVATION ON RABBIT BISECTED VAS DEFERENS STRIPS

1. In the present study, the effects of anandamide and WIN 55,212‐2, cannabinoid receptor agonists, were investigated on electrical field stimulation (EFS)‐induced biphasic twitch responses obtained from the epididymal and prostatic portions of rabbit vas deferens strips.

Investigation of enhancement effects of nicotine on cholinergic neurotransmission in isolated rabbit gastric fundus: role of antioxidants

Nicotine, which is tobacco alkaloid, still induces interests for researchers because of smokers addiction to nicotine. Nicotine having influence on the neuronal acetylcholine receptors (nAChRs) increases release of most certain neurotransmitters from the nerve endings. Also, nicotine, affecting the mitochondrial respiratory chains, contributes to the formation of reactive oxygen species. In the present study, we investigated the effects of nicotine on smooth muscles of gastric fundus on the electrical field stimulation (EFS) that induces transition contraction via stimulation nAChRs. In addition, we aimed to investigate the interaction between release of acetylcholine, induced by nicotine, and the effects of reactive oxygen species. Therefore, the effects of allopurinol (10(-6)-10(-5) M), deferoxamine (10(-4) M) and mannitol (10(-4)-5 x 10(-3) M) were tested on the transient contraction induced by nicotine. In conclusion, mannitol (5 x 10(-3) M) significantly reduced contractile response to nicotine on EFS only in high concentration. Whereas in small concentrations mannitol (10(-4) M) statistically did not cause any results. Deferoxamine and allopurinol also did not have any significant response.

Effects of platelet-activating factor on nitrergic transmission in rabbit corpus cavernosum

Abstract  Aim:  The information currently available suggests that nonadrenergic noncholinergic (NANC) transmitters, particularly nitric oxide, are involved in the relaxation of penile erectile tissues. Platelet‐activating factor (PAF) is a chemical mediator and is involved in many physiological and pathophysiological events. It is well known that several of the vascular actions of PAF are mediated by the generation of nitric oxide. We designed this study to test the hypothesis that PAF has an effect on NANC responses in rabbit corpus cavernosum strips.