The effects of different vasovasostomy techniques on motility of vas deferens (vas motility following vasovasostomy).

PURPOSE: Vasovasostomy is used to correct vas deferens (VD) transections encountered during surgery or to reverse sterilization vasectomies. Achieving vasal patency is the primary goal and the success is assessed on various factors including VD patency, flow rates, and pregnancy rates. While preserving vas motility is not a major concern in surgical practice, it is worth noting that VD has peristaltic activity which plays crucial role during ejaculation. Any disruption in its motility could potentially lead to negative outcomes in the future. We conducted an experimental study to assess vas motility changes following vasovasostomy. METHODS: The study was approved by Gazi University, Animals Ethic Committee. Twenty-four rats were allocated to four groups. Left-sided VD was harvested in control group (Gr1). The rest of the animals were subjected to transection of VD. Gr2 and 3 underwent microscopic and macroscopic anastomosis, respectively, while Gr4 underwent vasal approximation. After 12 weeks, all left-sided VD were resected, electrical field stimulation (EFS) and exogenous drugs were applied to induce contractions. Statistical analyses were performed and p value < 0.05 was regarded as statistically significant. RESULTS: The first and second phases of EFS-induced contractile responses(CR) increased for Gr3 and decreased for Gr4 at submaximal and maximal frequencies. An increase only at maximal frequency for second phase EFS-induced CR was encountered for Gr2. α-ß-methylene-ATP-induced CR decreased for Gr3 and 4. Noradrenaline-induced CR increased for Gr2, and 3 and decreased for Gr4. CONCLUSION: The results suggest that vasovasostomy performed using a surgical technique that minimizes disruption or damage to VD may have a favorable impact on motility.

Enhancing effect of nicotine on electrical field stimulation elicited contractile responses in isolated rabbit bladder straight muscle; the role of cannabinoid and vanilloid receptors.

BACKGROUND: Nicotine acts as an agonist of nicotinic acetylcholine receptors (nAChR). These receptors belong to a superfamily of ligand-gated ion channels. We previously demonstrated that nicotine increased electrical field stimulation (EFS)-induced contractile or relaxation responses, possibly by facilitating neurotransmitter release from nerve terminals in various rabbit tissues. Studies have shown that there is an interaction between the endocannabinoid and nicotinic systems. This study aimed to investigate the interaction between nicotine and the endocannabinoid system in the rabbit urine bladder and also investigate the enhancing effect of nicotine on EFS-induced contractile responses in rabbit isolated bladder smooth muscle and its interaction with the endocannabinoid system. METHODS: The New Zealand albino male adult rabbits were used for this study. Following scarification, the urine bladder was rapidly excised, and then uniform strips were prepared. Each strip was mounted under 1 g isometric resting tension in an organ bath containing 20 mL of Krebs-Henseleit solution. After obtaining EFS-induced contractile responses, 10-4 M concentrations of nicotine were applied to the preparations, and EFS was stopped after 5 stimulations. Following washing, the same experimental procedure was performed with the same tissue in the presence of AM251 (a cannabinoid CB1R antagonist, 10-6 M), AM630 (a cannabinoid CB2R antagonist, 10-6 M), and capsazepine (a vanilloid receptor antagonist, 3 × 10-6 M). RESULTS: Nicotine enhanced the EFS-induced contraction responses by 17.16% ± 2.81% at a 4-Hz stimulation frequency. Cannabinoid receptor antagonists AM251 and AM630 reduced this increasing effect of nicotine although it was not significant and vanilloid receptor antagonist capsazepine did not significantly alter the nicotines' effect. DISCUSSION: These results show that enhancing effect of nicotine in the smooth muscle of the rabbit bladder, even though it was not significant endocannabinoid system possibly have a role in nicotines' effect.

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

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, Nω -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.

Changes in cholinergic and nitrergic systems of defunctionalized colons after colostomy in rabbits.

BACKGROUND: This study was designed to assess smooth muscle function and motility in defunctionalized colonic segments and subsequent changes in pathways responsible for gastrointestinal motility. METHODS: Two-month-old New Zealand rabbits were randomly allocated into control and study groups. Sigmoid colostomies were performed in the study group. After a 2-month waiting period, colonic segments were harvested in both groups. For the in vitro experiment, the isolated circular muscle strips which were prepared from the harvested distal colon were used. First, contraction responses were detected using KCl and carbachol; relaxation responses were detected using papaverine, sodium nitroprusside, sildenafil, and l-arginine. The neurologic responses of muscle strips to electrical field stimulation (EFS) were evaluated in an environment with guanethidine and indomethacin. EFS studies were then repeated with atropine, Nω-nitro-l-arginine methyl ester, atropine, and Nω-nitro-l-arginine methyl ester-added environments. RESULTS: Although macroscopic atrophy had developed in the distal colonic segment of the colostomy, the contraction and relaxation capacity of the smooth muscle did not change. EFS-induced nitrergic-peptidergic, cholinergic-peptidergic, and noncholinergic nonnitrergic responses significantly decreased at all frequencies (0.5-32 Hz) in the study group compared with those in the control group (P < 0.05). CONCLUSIONS: Although the contraction capacity of the smooth muscle was not affected, the motility of the distal colon deteriorated owing to the defective secretion of presynaptic neurotransmitters such as acetylcholine, nitric oxide, and neuropeptides.

Effects of hydrogen sulfide on relaxation responses in the lower esophageal sphincter in rabbits: the potential role of potassium channels.

Hydrogen sulfide (H2S) is a significant physiologic inhibitory neurotransmitter. The main goal of this research was to examine the contribution of diverse potassium (K+) channels and nitric oxide (NO) in mediating the H2S effect on electrical field stimulation (EFS)-induced neurogenic contractile responses in the lower esophageal sphincter (LES). EFS-induced contractile responses of rabbit isolated LES strips were recorded using force transducers in organ baths that contain Krebs-Henseleit solutions (20 ml). Cumulative doses of NaHS, L-cysteine, PAG, and AOAA were evaluated in NO-dependent and NO-independent groups. The experiments were conducted again in the presence of K+ channel blockers. In both NO-dependent and NO-independent groups, NaHS, L-cysteine, PAG, and AOAA significantly reduced EFS-induced contractile responses. In the NO-dependent group, the effect of NaHS and L-cysteine decreased in the presence of 4-AP, and also the effect of NaHS decreased in the NO-dependent and independent group in the presence of TEA. In the NO-independent group, K+ channel blockers didn't change L-cysteine-induced relaxations. K+ channel blockers had no impact on the effects of PAG and AOAA. In addition, NaHS significantly relaxed 80-mM KCl-induced contractions, whereas L-cysteine, PAG, and AOAA did not. In the present study, H2S decreased the amplitudes of EFS-induced contraction responses. These results suggest that Kv channels and NO significantly contribute to exogenous H2S and endogenous H2S precursor L-cysteine inhibitory effect on lower esophageal sphincter smooth muscle.

Effects of cannabinoid and vanilloid receptor antagonists on nicotine induced relaxation response enhancement in rabbit corpus cavernosum.

Objectives: Endocannabinoids and nicotine regulate the neurotransmitter release in different central and peripheral synapses. Various studies in the literature demonstrate the interaction between endocannabinoid and nicotinic systems, especially in the central nervous system. The interaction between nicotinic and endocannabinoid systems was investigated in this study. We aimed to show the effects of cannabinoid and vanilloid receptor antagonists on nicotine-induced relaxation response increases in rabbit corpus cavernosum. Materials and Methods: From a total of seven male albino rabbits, three or four equal strips were cut from each corpus cavernosum and inserted in isolated organ baths. Tissues were contracted with phenylephrine (3×10-5 M). After contraction reached a plateau, strips were stimulated with EFS, and with the stabilization of EFS relaxation responses, 10-4 M of nicotine was administered to tissues. After that, in order to investigate the effects of AM251 (CB1 antagonist), AM630 (CB2 inverse agonist) or capsazepine (a vanilloid receptor antagonist) were given to different tissues, after the resting period. Results: Nicotine (10-4 M) increased the EFS-induced relaxation responses (14.60%±2.94%, P<0.05). AM630 decreased the enhancement of nicotine-induced EFS relaxation responses (nicotine 10-4 M enhancement: 17.16%±3.19%; nicotine 10-4 M enhancement in the presence of AM630 10-6 M: 4.44%±3.43% P<0.05; n=6), whereas effects of AM251 and capsazepine were not significant. Conclusion: In the present study, nicotine increased the amplitudes of EFS-induced relaxation responses probably via nicotinic acetylcholine receptors located on the nitrergic nerves of the corpus cavernosum. We showed the role of cannabinoid-like endo-ligands in nicotine-induced enhancement via CB2 receptors but not CB1 and VR1 receptors.

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.

Effect of a chloride channel inhibitor, 5-nitro-2- (3-phenylpropylamino)-benzoate, on endothelin-1 induced vasoconstriction in rabbit basilar artery.

AIM: Endothelin-1 (ET-1) has been implicated in the pathophysiology of cerebral vasospasm. Chloride (Cl-) channels exist in vascular smooth muscle and activation of these channels leads to depolarization and contraction. The aim of the present study was to test the effect of 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), a Cl- channel antagonist, on the ET-1-induced cerebral vasospasm in rabbit basilar artery and thus investigate the contribution of Cl- channels. MATERIAL AND METHODS: Thirty rabbits were divided into five groups and received intra-arterial injection of isotonic saline (Group I, n=6), ET-1 (group II, n=6), ET-1 plus NPPB (Group III, n=6), dimethylsulfate (DMSO4) (Group IV, n = 6) and NPPB (Group V, n=6). Pre and post injection basilar artery diameters were measured in each group and transmission electron microscopic investigations on basilar arteries were performed. RESULTS: The mean pre-injection and post-injection vessel diameters were 0.8833 mm and 0.7000 mm in ET-1 group, 0.6833 mm and 0.8500 mm in ET-1 + NPPB group. NPPB administered prior to ET-1 injection, prevented the ET-1-induced vasoconstriction. Additionally, NPPB prevents the ET-1 induced changes in vessel wall and neurons in the brain stem. CONCLUSION: The results of this study add further insights to our armamentarium against cerebral vasospasm.

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 nicotine's transient ability to augment neurogenic contractions and catalase (500 units/ml) enhanced the effect of nicotine.

Lack of nitrate tolerance in isosorbid dinitrate- and sodium nitroprusside-induced relaxation of rabbit internal anal sphincter.

AIM: To investigate the tolerance development against the relaxant effect of nitric oxide donating drug isosorbide dinitrate (ISDN) and sodium nitroprusside (SNP) in internal anal sphincter (IAS) smooth muscle. METHODS: Relaxation responses of ISDN, and electrical field stimulation (EFS) were obtained before and after tolerance induction by ISDN incubation. RESULTS: ISDN (10(-7)-10(-4) mol/L) and SNP (10(-8)-10(-4) mol/L) caused a concentration-dependent relaxation on the basal tonus of the isolated rabbit IAS strips. After a period of 2 h incubation of the 6 multiply 10(-4) mol/L ISDN the relaxation effects of ISDN and SNP did not change compared to control strips. EFS evoked frequency-dependent relaxation in internal anal sphincter smooth muscle and E(max) obtained from control strips were not changed in ISDN tolerance-inducing condition. In this study nitrate tolerance was not observed in rabbit IAS smooth muscle. CONCLUSION: This result shows that nitric oxide donating drugs relaxes the internal anal sphincter of the rabbits without the development of tolerance.

Evaluation of myorelaxant activity of 7-substituted hexahydroquinoline derivatives in isolated rabbit gastric fundus.

In this article, 16 new methyl(ethyl) 4-(dichlorophenyl)-2,7-dimethyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline-3-carboxylates and methyl(ethyl) 2-methyl-4-(dichlorophenyl)-5-oxo-7-phenyl-l,4,5,6,7,8-hexahydroquinoline-3-carboxylate derivatives have been synthesized by the Hantzsch reaction and screened for their myorelaxant and potassium channel opening activities. The maximum relaxant effects (E(max)) and pD(2) values on exogenous noradrenaline precontracted tissues and inhibitory effects on cholinergic neurotransmission of the compounds and pinacidil were determined on isolated strips of rabbit gastric fundus smooth muscle. Obtained results indicated that some compounds and pinacidil produced concentration-dependent relaxation on rabbit gastric fundus smooth muscle strips in the two test conditions.

Enhancement effects of nicotine on neurogenic contractile responses in rabbit gastric fundus.

Nicotine, a nicotinic acetylcholine receptor agonist, plays a role in the modulation of neurotransmitter release following nerve stimulation in both the central and the peripheral nervous system. Nitric oxide and prostaglandins modulate the release of various neurotransmitters in different tissues. We aimed to investigate the effects of nicotine on neurogenic contractile responses via nicotinic acetylcholine receptors and, if a change occurred, to investigate the effects of N(W)-nitro-L-arginine methyl ester (L-NAME) and indomethacin on this change in rabbit gastric fundus. Electrical field stimulation (EFS)-evoked contractile responses were recorded from gastric fundus strips obtained from rabbits with an isometric force displacement transducer. Nicotine was applied to preparations at varying concentrations. Then, the effects of hexamethonium, cadmium (Cd(2+)), indomethacin, and L-NAME were tested on the EFS-evoked contractions in the presence of nicotine. Nicotine-induced transient neurogenic contractions in a dose-dependent manner. Cd(2+) and hexamethonium inhibited nicotine-induced transient neurogenic contractions, but indomethacin and L-NAME produced no effect. In conclusion, nicotine increased EFS-evoked contractile responses, possibly by facilitating neurotransmitter 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 receptors in isolated rabbit gastric fundus. Endogenous nitric oxide and prostaglandins do not play a physiological role in the regulation of this neurotransmitter release.

Nicotine potentiates the nitrergic relaxation responses of rabbit corpus cavernosum tissue via nicotinic acetylcholine receptors.

The presence of neuronal nicotinic acetylcholine receptors in rabbit corpus cavernosum tissue and possible mechanisms underlying the potentiation of electrical field stimulation induced relaxation by nicotine were analyzed. In corpus cavernosum tissue strips nicotine (3 x 10(-5) M) and acetylcholine (10(-3) M) produced potentiation on electrical field stimulation (amplitude 50 V; frequency 4 Hz; width 0.8 ms) induced relaxation responses. This nicotine-induced potentiation was not altered by atropine (10(-6) M), guanethidine (5 x 10(-6) M) and indomethacin (10(-5) M), but abolished by hexamethonium chloride (10(-5) M) and L-nitro arginine methyl ester (10(-5) M). Nicotine did not cause any alteration on a single dose of carbachol (3 x 10(-5) M) and sodium nitroprusside (10(-5) M) induced relaxation responses. The results suggest that, nicotine-induced potentiation is NO and nicotinic acetylcholine receptor dependent but independent from prostaglandin synthesis, activation of muscarinic receptors and does not require intact adrenergic neurons. Nicotine did not affect smooth muscle and endothelium directly. In conclusion, in this study we showed for the first time that, nicotine acts on the nicotinic acetylcholine receptors located on the nitrergic nerves, thereby evoking the release of NO from these nerve terminals inducing relaxation response in rabbit corpus cavernosum tissue.

Nicotine potentiates the neurogenic contractile response of rabbit bladder tissue via nicotinic acetylcholine receptors: nitric oxide and prostaglandins have no role in this process.

Nicotine, a nicotinic acetylcholine receptors (nAChRs) agonist, has a role in modulation of the neurotransmitter release following nerve stimulation in both the central and peripheral nervous systems. The aim of this study was to determine whether electrical field stimulation (EFS)-evoked contractions are altered in rabbit bladder in the presence of nicotine and, if an alteration occurs, to investigate the effects of nitric oxide and prostaglandins on nicotine-induced alternation in isolated rabbit bladder. EFS-evoked contractile responses from rabbit bladder obtained were recorded with isometric force displacement transducers. Nicotine was added to preparations at various concentrations. The effects of hexamethonium, cadmium (Cd(2+)), indomethacin and N-nitro-L-arginine methyl ester (L-NAME) were tested on the EFS-evoked contractions in the presence of nicotine. Nicotine led to a dose-dependent increase in the amplitude of the EFS-evoked contractile responses. Cd(2+) and hexamethonium inhibited the nicotine-induced increase in EFS-evoked responses, whereas indomethacin and L-NAME had no effect. In conclusion, nicotine increased the EFS-evoked contractile responses possibly by facilitating release of neurotransmitters from nerve terminals by a mechanism dependent on the influx of Ca(2+) from voltage-gated Ca(2+) channels (VGCCs) via activation of nAChRs in isolated rabbit bladder. Nitric oxide and prostaglandins do not have a physiological role in the regulation of neurotransmitter release.

Torsion/detorsion of the testis does not modify responses to nitric oxide in rat isolated penile bulb.

Ischaemia-reperfusion damage induced by torsion/detorsion of the testicles may be a causative factor leading to erectile dysfunction through oxidative stress-dependent changes in the responses of the penile bulb, an erectile tissue of the penis. We aimed at investigating the effects of unilateral testicular torsion/detorsion (2 or 24 hr) treatment on relaxations induced by electrical field stimulation and sodium nitroprusside in rat isolated penile bulb. Male Sprague-Dawley rats used in the study were divided into two groups. The treatment group was subjected to unilateral torsion followed by detorsion for 2 or 24 hr, while the control group underwent only sham operation. For in vitro organ bath experiments, penile bulbs were isolated and responses to relaxant agents and electrical field stimulation (70 V, 1 msec., 0.5-8 Hz, 5 sec.) were recorded on a computer-based data acquisition system via a force displacement transducer. In tissues precontracted with phenylephrine (3 x 10(-6 )M), relaxations induced by electrical field stimulation were not significantly different before and after 2 or 24 hr of detorsion. Similarly sodium nitroprusside- (10(-8)-3 x 10(-6 )M) and papaverine-induced (10(-7)-10(-4 )M) relaxations were also found unchanged in the detorsion group compared to control. In conclusion, spermatic cord torsion did not lead to impairment in nitric oxide-mediated relaxant responses of the rat isolated penile bulb.

Agmatine facilitates sympathetic neurotransmission in frog myocardium via an action on alfa 2-adrenergic receptors.

OBJECTIVE: In this study, the effect of agmatine was studied on sympathetic neurotransmission in the frog isolated ventricular strips. METHODS: Ventricular strips were prepared from the heart of the pitched frog. Each strip was mounted vertically in an organ bath. Muscle contractions were recorded isometrically by a force displacement transducer and displayed on a polygraph. RESULTS: Concentration-response relationships to noradrenaline were obtained on contractility of frog ventricular strips evoked by electrical stimulation. The responses of noradrenaline were re-obtained in presence of agmatine (3X10(-4) M). Agmatine was found to be ineffective on contractile responses of noradrenaline in electrically driven ventricular strips of frog heart. Transient additional stimulations (TAS) induced contractions. The contractions induced by TAS were re-obtained in presence of agmatine, idazoxan + agmatine and yohimbine + agmatine. Agmatine significantly increased the positive inotropic responses of TAS. The effect of agmatine on contractile responses of TAS was not changed by idazoxan, indicating that imidazoline receptors have not functions in this response. The effect of agmatine on the contractile responses to TAS was reversed by yohimbine, indicating involvement of alpha2 adrenoceptors in this response. Agmatine did not change the contractile responses of ventricular strips to exogenous noradrenaline, indicating that agmatine does not affect postjunctional adrenoceptors. CONCLUSION: These results suggest that agmatine facilitates sympathetic neurotransmission in frog myocardium via an action on prejunctional alpha2 adrenergic receptors located on sympathetic nerve terminals.

Effects of chronic l-DOPA administration on neurogenic and endothelium-dependent relaxation responses in rabbit corpus cavernosum.

BACKGROUND: Dopamine is a crucial central neurotransmitter that plays a fundamental role in the autonomic and somatic components of penile reflexes in animals and humans. Similar to the erectile responses of dopamine, systemic administration of l-DOPA induces yawning and penile erection in some species. The possible effects of l-DOPA on nitric oxide (NO)-dependent and -independent non-adrenergic non-cholinergic (NANC) relaxation responses mediated by electrical field stimulation (EFS) and endothelium-dependent relaxation were investigated in this study. METHODS: Thirty-two adult albino male rabbits, in two- and four-week-treatment groups, were divided into three subgroups: control group (saline-injected) (n=4), 3mg/kg/day (low dose) l-DOPA-injected groups (n=6) and 12mg/kg/day (high dose) l-DOPA-injected groups (n=6). After the intraperitoneal injection treatments, the corpus cavernosum tissues were placed in organ bath chambers. The EFS-mediated responses, and the concentration-response curve to carbachol, sodium nitroprusside (SNP), sildenafil were assessed. RESULTS: The two-week treatment with high-dose l-DOPA decreased the NO-dependent NANC relaxation responses, while there was no change in the low-dose two- and four-week treatment groups. The NO-independent NANC relaxation responses in the two-week groups decreased, and the responses in the four-week groups were unchanged when compared to the controls. The relaxation responses to carbachol showed no differences among all groups except for the high-dose four-week l-DOPA group. The relaxation responses of SNP and sildenafil were increased in all of the treatment groups when compared to the controls. CONCLUSIONS: The observed increases in SNP- and sildenafil-induced responses, along with the decreased EFS-mediated responses, suggest increased sensitivity in the NO-signalling pathway following l-DOPA administration.

The effects of hydrogen sulfide on electrical field stimulation-induced neurogenic contractile responses in isolated rabbit lower esophageal sphincter: Contribution of nitrergic and non-adrenergic non-cholinergic transmission.

BACKGROUND: Hydrogen sulfide (H2S) is a gaseous signaling molecule that, similar to nitric oxide (NO), plays an important role as an inhibitor neurotransmitter in the digestive tract. This study aimed to investigate the effect of H2S and to identify neurogenic contraction responses dependent on the electrical field stimulation (EFS) in the isolated lower esophageal sphincters of rabbits. METHODS: An isolated lower esophageal sphincter was placed in an organ bath system and mechanical responses were recorded using a force transducer. The nerve-evoked contractile responses were obtained by EFS. The contractile responses were obtained as biphasic "on" and "off" phases seen at the beginning and end of EFS, respectively. RESULTS: Sodium hydrogen sulfide (NaHS) reduced the EFS-mediated "off" phase and the EFS-mediated non-adrenergic non-cholinergic (NANC) "off" phase. NaHS reduced the EFS-mediated "on" phase as well. l-Cysteine ​​reduced the EFS-mediated "off" phase and the EFS-mediated NANC "off" phase. l-Propargylglycine (PAG) did not affect the EFS-mediated "off" phase or the EFS-mediated NANC "off" phase. NaHS, l-cysteine, and PAG reduced the EFS-mediated, NO-independent "off" phase. The effect of NaHS in all of the experiments returned in time. Also, NaHS caused significant relaxation of 80-mM KCl-Krebs solution induced-contractions, while l-cysteine ​​and PAG did not cause a significant relaxation. CONCLUSION: These findings suggest that H2S has an inhibitory effect on the lower esophageal sphincter muscle. While the effect of H2S on EFS-mediated responses disappeared in time, the effect of H2S sustained the KCl-Krebs solution-induced contractions. This shows that H2S may have an effect on neurotransmission at the nerve terminal.

Enhancement of EFS-induced contractions, by agmatine, in guinea pig gallbladder smooth muscle strips.

BACKGROUND: Electrical field stimulation of gallbladder muscle strips produces frequency-dependent contractions by activating cholinergic nerves. The cholinergic motor function of the gallbladder and enteric system is also modulated by other mediators. The aim of this study was to investigate the role of agmatine, a ligand for alpha 2-adrenoceptors and imidazoline binding sites, in the cholinergic motor activity of guinea pig gallbladder smooth muscle. METHODS: Gallbladder muscle strips obtained from guinea pigs were subjected to electrical field stimulation (1-64 Hz, 100 V, 1-ms pulse width, and 10-s train duration). Frequency-response contractions of gallbladder muscle strips were traced before and after the addition of cumulative concentrations of agmatine (10(-5)-10(-3) M) to the tissue bath. The same set of experiments was repeated in the presence of different antagonists. RESULTS: Agmatine by itself did not produce any contractions in guinea pig gallbladder muscle strips, but significantly enhanced the contractile response produced by electrical field stimulation. Yohimbine (10(-6) M), a selective alpha 2-adrenergic blocker, neither decreased nor increased the enhancement induced by agmatine. However, idazoxan (10(-4) M), an alpha-receptor blocker and imidazoline receptor antagonist, abolished this enhanced contractile response. Pretreatment with N(W)-nitro L-arginine methyl ester (L-NAME; 30 microM), and indomethacin (10 microM) did not inhibit the effect of agmatine. CONCLUSIONS: Our findings indicate that agmatine has a modulator role in the electrical field stimulation-induced cholinergic contractions of guinea pig gallbladder smooth muscle strips, and this role could be mediated by imidazoline receptors. Receptor binding studies should be done to determine the presence of endogenous agmatine and imidazoline receptors in gallbladder smooth muscle.

The effects of melatonin on electrical field stimulation-evoked biphasic twitch responses in the ipsilateral and contralateral rat vasa deferentia after unilateral testicular torsion/detorsion.

It is not known whether there is an impairment in vas deferens motility after unilateral testicular torsion/detorsion. Therefore, we aimed to determine whether the electrical field stimulation (EFS)-evoked biphasic contractions are altered in ipsilateral and contralateral rat vasa deferentia obtained from animals exposed to the unilateral testicular torsion/detorsion procedure. We also evaluated the effects of melatonin (MLT), which is a strong antioxidant, on these contractile responses. Rats were subjected to torsion of the left testis for 2 h and then detorsion was performed. Contractility studies were carried out 2 h or 24 h after detorsion. Vas deferens strips were prepared from both the ipsilateral and the contralateral site 2 h or 24 h after the detorsion procedure to record EFS-evoked biphasic twitch responses. The same experimental protocol was repeated for the MLT-treated rats. Both phases of EFS-evoked contractions were decreased after torsion/detorsion in the ipsilateral vas deferens. MLT treatment increased torsion/detorsion-induced reduction of both phases of contractions after 2 h and 24 h. In the contralateral vas deferens, the first phase of EFS-evoked contractions was not changed, while the second phase of contractions was diminished 2 h and 24 h after detorsion. Although MLT decreased the second phase of contractions 2 h and 24 h after detorsion, it reduced the first phase of contractions only 2 h after detorsion. These results suggest that MLT produces an inhibition on EFS-evoked biphasic twitch responses in the ipsilateral and contralateral rat vasa deferentia following unilateral testicular torsion/detorsion in the rat.