Mechanism of acitretin-induced relaxations in isolated rat thoracic aorta preparations.

Acitretin is a member of vitamin A-derived retinoids, and its effect on vascular smooth muscle had not yet been studied. The aim of this study is to investigate the effect of acitretin, a retinoid, on vascular smooth muscle contractility. Thoracic aorta preparations obtained from 34 male Sprague-Dawley rats (355 ± 15 g) were studied in isolated organ baths containing Krebs-Henseleit solution. The relaxation responses were obtained with acitretin (10-12-10-4 M) in endothelium-preserved and endothelium-denuded aorta preparations precontracted with submaximal concentration of phenylephrine (10-6 M). The role of retinoic acid receptors (RARs), nitric oxide, adenylyl, and guanylyl cyclase enzymes, and potassium channels in these relaxation responses were investigated. Acitretin produced concentration-dependent relaxations, which were independent of its solvent dimethylsulfoxide (DMSO), in endothelium-denuded phenylephrine-precontracted thoracic aorta preparations. While incubation with the RAR antagonist (AGN193109, 10-5 M) had no effect on these relaxations; nitric oxide synthase inhibitor (L-NG-Nitro arginine methyl ester (L-NAME), 10-4 M), adenylyl cyclase inhibitor (SQ2253, 10-5 M), guanylyl cyclase inhibitor (oxadiazolo [4,3-a] quinoxalin-1-one (ODQ), 10-6 M), and potassium channel blocker (tetraethylammonium (TEA), 10-2 M) significantly eliminated the relaxation responses induced by acitretin. Acitretin induces relaxation in rat isolated thoracic aorta preparations without endothelium, which may be mediated by nitric oxide, cyclic adenosine monophosphate, and cyclic guanosine monophosphate-dependent kinases and potassium channels.

Effects of ozone therapy and taurine on ischemia/reperfusion-induced testicular injury in a rat testicular torsion model.

BACKGROUND/AIM: To investigate the effect of ozone and/or taurine treatment comparatively on testicular damage due to ischemia/ reperfusion (I/R) injury in an experimental torsion model in rats. MATERIALS AND METHODS: Adult Wistar rats with and without torsion/detorsion were used. In order to monitor the effect of ozone and/or taurine treatment on testicular damage due to I/R injury, following histopathological investigation apoptotic indexes were scored by TUNEL method. Moreover, tumor necrosis factor receptor 1 (TNFR1), caspase 3, caspase 8, endothelial nitric oxide synthase (eNOS), tumor necrosis factor alpha (TNFα), and cytochrome C immunostainings were performed and the levels of malondialdehyde, glutathione peroxidase, superoxide dismutase, catalase, total sulfhydryl, and nitric oxide were determined in the testicular tissue. RESULTS: Intraperitoneal ozone and/or taurine treatment prevented both histopathological damage and increase in the apoptotic index. Torsion did not exert an effect on the levels of TNFα and cytochrome C. Ozone and/or taurine treatment prevented increases in TNFR1, caspase 3, and caspase 8. The level of oxidative stress markers was unchanged. The increases in NO level and eNOS expression were prevented by ozone and/or taurine treatment in I/R groups. CONCLUSION: Using ozone therapy and/or taurine before reperfusion may be a solution for germ cell degeneration resulting from testicular torsion and related infertility.

Apoptosis in testicular tissue of rats after vasectomy: evaluation of eNOS, iNOS immunoreactivities and the effects of ozone therapy.

OBJECTIVE: We aimed to investigate the changes in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression and apoptotic index in rat testicular tissue, as well as serum and seminal plasma sex hormone levels after vasectomy, and the effect of ozone therapy (OT). MATERIAL AND METHODS: Adult male Wistar rats were used (n=6 per group). Control (G1), sham for 4 weeks (G2) or 6 weeks (G3), orchiectomy at the 4(th) (G4) or 6(th) (G5) week after left vasectomy, orchiectomy at the 4(th) (G6) or 6(th) (G7) week after bilateral vasectomy, orchiectomy after 6 weeks OT following left (G8) or bilateral (G9) vasectomy, orchiectomy after 6 weeks OT (G10). RESULTS: In the left testes, while there were increases in eNOS and iNOS immunoreactivity and apoptotic indexes in G4 and G5, no changes were observed in contralateral testis. These values increased in G6 and G7, while OT inhibited these parameters in the left testis of G8 and both testes of G9. Sex hormone levels did not show any changes after vasectomy and ozone therapy. CONCLUSION: While OT was found to be protective against some parameters mentioned above under stress conditions, it seemed to cause some harmful effects when used in healthy conditions.

Effect of phototherapy on gastrointestinal smooth muscle activity and oxidative stress.

AIM: To evaluate the effect of phototherapy on gastrointestinal smooth muscle activity and oxidative stress. METHODS: Wistar albino rats (n = 18, in the first 7 days of life) weighing 7 ± 2 g with both sexes were included in the study. The animals were randomized into three groups. In control group (CG), median laparotomy was performed to obtain 1 cm of jejunum, terminal ileum and colonic segments. In the phototherapy group (PTG), led phototherapy with a wave density of 40 µw/cm(2)/nm were used (Bilitron 3006, Fanem, Brasil). The efficacy surface of phototherapy was 30-40 cm and the exposure distance was 30 cm. The duration of phototherapy was 24 h. Sham group (SG) received white light with the same wave density and exposure distance. The oxidative stress markers and contraction responses were investigated from intestinal segments obtained from experiments. RESULTS: The jejunum segments showed significantly lowered contraction response to carbachol in SG when compared to CG and PTG (p < 0.05). Decreased contractile response to KCl was detected in both SG and PTG in terminal ileum segments. MDA levels showed no difference between groups (p > 0.05). Total sulfhydryl (T-SH) levels were found significantly increased in PTG when compared to CG and SG (p < 0.05). When NO levels were evaluated, NO levels were found decreased in PTG and SG with respect to CG (p < 0.05). CONCLUSION: PT may cause various alterations in oxidant/antioxidant system in intestinal segments. Unlike to clinical findings, decreased contractile responses were detected in rat gastrointestinal smooth muscles after PT.

The effects of beta-blockers on endothelial nitric oxide synthase immunoreactivity in the rat corpus cavernosum.

OBJECTIVES: To explain the mechanism of the effects of beta-blockers on endothelial dysfunction and release of nitric oxide from the endothelium. METHODS: A total of 72 Sprague-Dawley rats were divided into 9 different groups as follows: group 1: control (n = 10), group 2: metoprolol (Beloc) 100 mg/kg/d (n = 7), group 3: carvedilol (Dilatrend) 50 mg/kg/d (n = 7), group 4: nebivolol (Vasoxen) 10 mg/kg/d (n = 6), group 5: estrogen receptor (ER) antagonist ICI 182.780 (Fluvestrant) 50 microg/g (n = 10), group 6: nebivolol+ER antagonist (n = 8), group 7: androgen receptor (AR) antagonist (flutamide) 20 mg/kg (n = 7), group 8: nebivolol+AR antagonist (n = 7), and group 9: DMSO (solvent for ER antagonist) (n = 10). All beta-blockers were applied with gastric gavage after dilution with 5 mL of serum physiological; ER and AR were both applied intraperitoneally (i.p.) for 14 days. In the isolated rat cavernous tissues, endothelial nitric oxide synthase (eNOS) and ER and AR immunoreactivity were analyzed quantitatively. One-way analysis of variance and Tukey test were used for statistical analysis. RESULTS: Although increased eNOS immunoreactivity was observed with nebivolol and nebivolol-flutamide in endothelial cells laying cavernous tissue, a lower score was observed after ICI-182.780 application, when compared with control cases. AR immunoreactivity in cavernosal endothelium was clearly higher with nebivolol. Higher H score and ER immunoreactivity were observed in the cavernous endothelium and smooth muscles in the nebivolol, carvedilol, and metoprolol groups when compared with control cases. CONCLUSIONS: We showed that eNOS activity was increased in the nebivolol and nebivolol-flutamide groups, whereas it was decreased in the ICI 182.780 group. We believe that an ER-dependent mechanism triggered by nebivolol played a role in nitric oxide formation.

Effect of whole gut irrigation solutions on gastrointestinal smooth muscle activity.

BACKGROUND/PURPOSE: It has been suggested that whole gut irrigation (WGI), which is a preparation method for large bowel surgery or colonoscopy, increases gastrointestinal motility by creating a gastrocolic reflex. An experimental study was performed to evaluate the effect of different WGI solutions on gastrointestinal smooth muscle activity. MATERIALS AND METHODS: Thirty Wistar albino rats weighing 200 to 250 g were enrolled in the study. After anesthetization with thiopental sodium (50 mg/kg), proximal ileum, terminal ileum, and colon segments were removed via median laparotomy to obtain a control group. Four different groups (n = 6) were designated as having WGI with saline solution (SS), lactated Ringer's solution (RL), polyethylene glycol (PEG), and dibasic sodium phosphate (DNP). Bowel cleaning was performed by infusing solutions at a rate of 2 mL/min via gastric tube, until the stool was cleared. After completing the bowel cleaning, 2 cm of tissues were removed and suspended in Tyrode solution in an isolated organ bath with a resting tension of 1 g, to obtain carbachol and potassium chloride (KCl) responses. RESULTS: The mean bowel cleaning times were 87.5 +/- 9.35, 81.6 +/- 9.83, 86.6 +/- 11.6, and 85.0 +/- 0.0 minutes in SS, RL, PEG, and DNP groups, respectively. The total amounts of solutions needed for cleaning were 156.67 +/- 21.6, 195.0 +/- 20.0, 197.5 +/- 32.8, and 70.0 +/- 0.0 mL, respectively. Although there was no difference in cleaning time between the groups, the amount of solution required was significantly less in the DNP group (P = .02). In the proximal ileum segments, though there was no difference in carbachol responses between groups, KCl responses were significantly increased in the RL group (P < .05). When we evaluated the terminal ileum responses, carbachol responses were significantly increased in RL and PEG groups (P = .011) and decreased in the DNP group (P = .049). The KCl responses were also significantly increased in the RL group with respect to the other groups (P < .05). Colon segments showed no difference in contractile responses with respect to different WGI solutions (P > .05, analysis of variance, post hoc Dunn's test). CONCLUSION: The different WGI solutions demonstrated no significant differences in colon contractions. The increased contractile responses in the proximal and terminal ileum segments after WGI with RL may be related to the electrolyte composition of RL. Although the lower amount of DNP solution required to achieve bowel cleaning seems to be an advantage, the decreased ileal contractions can be assessed as a disadvantage of DNP irrigations.

In vitro sensitivity of mouse esophagus to agonists in different pH medium values.

AIM: The aim of this study is to determine the in vitro sensitivity of mouse esophagus to contracting and relaxing agonists in different pH medium values. MATERIALS AND METHODS: Forty-eight Swiss albino mice (30-40 g) of both sexes were anesthetized with tiopental sodium (30 mg/kg). After exsanguinations from abdominal artery, esophagi were removed and suspended under 0.6 g of resting tension in a tissue bath containing 10 mL of Krebs solution at 37 degrees C. The experiments were performed in different pH mediums 7.4, 6.4, 4, and 2. Carbachol and acetylcholine were used as contractile agonists, and noradrenalin and isoproterenol to evaluate relaxation responses. Data concerning similar concentrations of contractile agonists obtained from different pH mediums were analyzed using Kruskal-Wallis nonparametric analysis of variance and post hoc Dunn test. Relaxation responses were compared with Student t test. A P value less than .05 was considered significant. The study was approved by Local Ethical Committee of Kirikkale University. RESULTS: Carbachol and acetylcholine caused concentration-dependent contractility in pH 7.4, 6.4, and 4, but contractile responses were inhibited in pH 2. In carbachol and acetylcholine experiments, there was a significant decrease in contractile responses to all concentrations in conjunction with a decreased in pH value. Relaxation responses in pH 2 and 4 could not be obtained because precontraction of tissues was not possible. Noradrenalin and isoproterenol produced concentration-dependent relaxations in pH 7.4 and 6.4. Although noradrenalin responses showed no significant difference according to pH, isoproterenol caused better relaxations in pH 6.4 (between 10(-8) and 10(-6) mol/L) when compared to pH 7.4 studies. CONCLUSION: The mouse esophagus has impaired contractile responses to carbachol and acetylcholine in decreased pH values. Contraction responses did not occur in pH medium of 2. In contrast, esophagus segments showed better relaxations in lower pH values with isoproterenol.