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.

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.

Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds.

This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to affect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profile of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photo-product. Pharmacological tests on the molecules showed a good muscle relaxing effect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.

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.

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.

Microwave-assisted synthesis and myorelaxant activity of 9-indolyl-1,8-acridinedione derivatives.

In this study a microwave-assisted method was applied for the synthesis of novel 9-(substituted indolyl)-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione derivatives. The structures of the compounds were confirmed by spectral methods including X-ray studies and elemental analysis. The Emax and pD2 values of the compounds and pinacidil were determined on noradrenaline precontracted tissues of isolated strips of rabbit gastric fundus smooth muscle. The obtained results indicated that some compounds and pinacidil produced concentration-dependent relaxation on the strips. The efficacy of compound 9 was higher than pinacidil. Docking studies were carried out to understand the interactions of the compounds with the active site of potassium channel. Methyl substituents on the acridine backbone and bromine atom on the indole ring led to more active compounds.