Effects of the Oxytocin Hormone on Pelvic Floor Muscles in Pregnant Rats.

Background and Objectives: Oxytocin induction is a known risk factor for pelvic floor disorders (PFDs). The aim of the study was to investigate the effects of oxytocin induction on pelvic floor muscles in pregnant rats. Methods: Thirty-two female Wistar rats were included and divided into four groups (n = 8). The groups were as follows: virgin group (group I)-from which muscles were dissected at the beginning of the experiment; spontaneous vaginal delivery (group II) which has delivery spontaneously; saline control group (group III) and oxytocin group (group IV). In groups III and IV, pregnancy was induced on d 21 of pregnancy, with 2.5 mU saline solution or iv oxytocin, respectively, delivered by the intravenous (iv) route in pulses at 10-min intervals for 8 h. Then, the rats were euthanized, the m. coccygeus, m. iliocaudalis and m. pubocaudalis muscles were excised and tissue samples were taken. After histological processing, the vertical and horizontal dimensions of the muscles were analyzed under a light microscope. Results: In group IV; the measurement of the horizontal dimension of the m. pubocaudalis muscles was 50.1 ± 5.4 µm and it was significantly higher than other groups (p < 0.001). In group III; the mean value of the horizontal dimension of m. coccygeus muscle was found to be 49.5 ± 10.9 µm and it was significantly higher than other groups (p < 0.009). Between-group comparisons revealed no difference in mean m. iliocaudalis muscle dimension (p > 0.05). Conclusions: As a result of our study it can say that whether oxytocin induced or not, vaginal birth is a process that affects the pelvic muscles.

BK channel openers NS1619 and NS11021 reverse hydrogen peroxide-induced membrane potential changes in skeletal muscle.

Large conductance calcium-activated potassium (BK) channels play a crucial role in the repolarization and after-hyperpolarization phases of the cell membrane. The channel openers are also used in treatment of some diseases, including hypo/hyperkalemic periodic paralysis. However, little is known about the effects of BK channels and the channel activators on membrane potentials in skeletal muscle. In addition, the effects of reactive oxygen species (ROS) on BK channels in skeletal muscle are also unknown. Therefore, the aim of this study was to determine the effects of BK channel openers and ROS on membrane potentials in skeletal muscle fibers. For this purpose, resting membrane potentials and action potentials (AP) of frog gastrocnemius muscles were recorded in the presence of commonly used BK channel openers NS1619 and NS11021, H2O2 (a type of ROS), and both using intracellular microelectrode technique. The channel activators significantly and dose-dependently decreased amplitude and increased rise time of AP but did not impact repolarization. The presence of H2O2 plus NS1619 or NS11021 resulted in significant change because the channel openers completely reversed the deleterious effects of hydrogen peroxide on the repolarization phase of AP in skeletal muscle fibers. In the present study, the contributions of BK channel activation and the modulatory role of H2O2 on membrane potentials was demonstrated in skeletal muscle fibers, for the first time. Moreover, it should be noted that BK channel openers should be used in the treatment of reactive oxygen species-induced skeletal muscle diseases.

The effect of Ferula elaeochytris root extract on erectile dysfunction in streptozotocin-induced diabetic rat.

Erectile dysfunction (ED) is an important complication of diabetes. The aim of our study was to determine whether Ferula elaeochytris (FE) root extract could affect ED in streptozotocin (STZ)-induced diabetic rats. Seventy-five adult male Wistar albino rats were equally divided into five groups; control (C), FE (40 mg/kg-d), STZ-induced diabetes (60 mg/kg) (DM), diabetes + F. elaeochytris (DM + FE), and ethanol (EtOH). After 8 weeks, in vitro and in vivo parameters (intracavernosal pressure [ICP]), testicle and body weight, serum glucose levels, and histopathology were assessed. In the STZ-induced diabetic group, acetylcholine-induced endothelium-dependent relaxation responses, and electrical field stimulation-induced neurogenic and nitrergic relaxation responses were decreased significantly, while FE administration to diabetic rats reversed the decreased nitrergic and neurogenic responses. In the diabetic group, ICP/MAP (0.1375 ± 0.02 cm/H2O), spermatogenesis in testicles (53.73 ± 0.81), and testicle weights (257.8 ± 20.63) were decreased significantly; however, FE administration to diabetic rats restored the decreased values (0.350 ± 0.019 cm/H2O, 75.07 ± 0.35, and 416 ± 24.11, respectively). In the DM group, blood glucose levels were increased (411.7 ± 18.30) compared to the C group. However, FE administration to diabetic rats reduced glucose levels (230.6 ± 25.60 mg/dL) compared to the DM group. In conclusion, FE recovered neurogenic and endothelial dysfunction and decreased glucose levels in diabetic rats.

Early propranolol treatment ameliorates endothelial dysfunction in experimental septic lung.

BACKGROUND: Recent reports have indicated an improved prognosis in sepsis with ß-blocker agents; however, the underlying action mechanism is still under debate. OBJECTIVES: The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats. MATERIAL AND METHODS: The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation. RESULTS: Serum tumor necrosis factor alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the preand post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells. CONCLUSIONS: These results suggest that the improved outcome with ß-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of ß-blockers on the endothelium may lead to a better understanding of sepsis.

Pharmacological profile of a nitric oxide donor spermine NONOate in the mouse corpus cavernosum.

BACKGROUND/AIM: To investigate the effects of spermine NONOate in the cavernous tissue obtained from mice treated or untreated with sildenafil. MATERIALS AND METHODS: We studied the effects of spermine NONOate on the tone and nitrergic relaxation responses of isolated mouse corpus cavernosum and compared them with sodium nitroprusside in the absence or presence of L-nitroarginine, hydroxocobalamin, pyrogallol, diethyldithiocarbamate (DETCA), or 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The neurogenic contractions and relaxations of the tissues were induced by electrical field stimulation. Some mice received a single oral dose of sildenafil and after 1 h the effects of spermine NONOate were evaluated by in vitro studies. RESULTS: Spermine NONOate relaxed mouse corpus cavernosum in a concentration-dependent manner. Spermine-NONOate-induced relaxation was relatively slow to develop and it was reversible and reproducible. These relaxations were significantly suppressed by hydroxocobalamin, diethyldithiocarbamate, or ODQ, but not by L-nitroarginine or pyrogallol. Spermine NONOate potentiated the nitrergic relaxations to electrical field stimulation (EFS), whereas it significantly reduced EFS-induced contractions. Sildenafil treatment can enhance the relaxant responses to spermine NONOate and EFS. CONCLUSION: These findings suggest that spermine NONOate has a potent relaxant action in cavernous tissue and this effect can be potentiated by oral sildenafil treatments. Spermine NONOate may be considered an attractive treatment for erectile dysfunction in pathologic disorders with a lack of endogenous NO production.

Effect of silymarin on bladder overactivity in cyclophosphamide-induced cystitis rat model.

The purpose of this study was to investigate the effects of silymarin, a phytotherapeutic agent, on bladder overactivity in a cyclophosphamide (CYP)-induced cystitis rat model. Female Wistar Albino rats received a single intraperitoneal injection of CYP (150 mg/kg) or saline and after 72 h, bladder function was evaluated by in vitro preparations of whole bladders and cystometry with continuous saline infusion under urethane anesthesia. Silymarin or a vehicle was orally given for 7 days in rats. CYP was injected on the 5th day of silymarin or vehicle treatment and then the animals were killed on the 8th day. CYP-treatment dramatically potentiated the basal spontaneous contractions of isolated whole bladders compared to control rats. In anesthetized rats, during continuous infusion cystometry, intercontraction interval (ICI) was significantly shorter, but bladder voiding pressure was not significantly changed in CYP-injected rats compared to control rats. In the CYP-injected group, silymarin treatment significantly decreased the amplitude, frequency (contractions/min) and area under the curve of spontaneous contractions, but failed to change carbachol-induced contraction in isolated whole bladder. Also, silymarin treatment significantly increased the ICI in comparison to the vehicle treatment. In the saline-injected group, no significant changes in the bladder function were observed between the silymarin and vehicle-treated groups. Histopathological examination showed that CYP-induced bladder inflammation tended to be lower in the silymarin+CYP-treated group. In conclusion, the oral administration of silymarin suppressed CYP-induced bladder overactivity. Silymarin may be considered as an attractive treatment for CYP-induced bladder overactivity.

Effects of vitamin E and sodium selenate on impaired contractile activity by bacterial lipopolysaccharide in the rat vas deferens.

We investigated whether bacterial lipopolysaccharide (LPS) treatment causes any hyporeactivity in rat vas deferens tissue and also whether vitamin E or sodium selenate has any restorative effect on this possible hyporesponsiveness. LPS treatment attenuated contractions to electrical field stimulation (EFS), phenylephrine, or ATP at the prostatic and epididymal ends. Treatment with the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine or vitamin E could prevent the impairment in contractile responses of both ends to EFS and phenylephrine but sodium selenate could restore these impaired contractions at only the epididymal end. LPS treatment also caused a similar significantly impairment on purinergic or adrenergic component of nerve-evoked contractions in the presence of prazosin or suramin, respectively, and vitamin E or sodium selenate could restored this impairment at both ends. On the other hand, both antioxidant agents failed to restore the impaired ATP-induced contractions in LPS-treated rats at both ends. In conclusion, LPS-treatment caused a hyporeactivity in the rat vas deferens. A possible increased oxidative activity in the vas deferens may be a major reason for the impairment of contractile responses. The restorative effects of vitamin E and/or sodium selenate on this hypocontractility may depend on their antioxidant properties or their inhibitory action on the iNOS.

Differential effect of neocuproine, a copper(I) chelator, on contractile activity in isolated ovariectomized non-pregnant rat, pregnant rat and pregnant human uterus.

The study was conducted to examine effects of a selective copper(I) chelator, neocuproine on the spontaneous or oxytocin-induced contractions in isolated ovariectomized non-pregnant rat, pregnant rat and pregnant human uterus. Uterus activity was evaluated in tissues obtained from bilaterally ovariectomized non-pregnant rats on the 21st day of the operation (n = 24), pregnant rats on the 19-21st day of gestation (n = 24) and women undergoing caesarean section at 38-42 weeks of pregnancy (n = 15). Neocuproine (100 microM) significantly suppressed the amplitude and frequency of the spontaneous contractions in the ovariectomized non-pregnant rat uterus while this agent facilitated the frequency of the spontaneous or oxytocin-induced contractions in the pregnant rat and human uterus without altering the amplitude of these contractions. At high concentration of 200 microM, neocuproine could enhance the amplitude of the contractions in the pregnant uterus. These effects were blocked by a purinergic receptor antagonist, suramin (100 microM) and did not occur following the administration of neocuproine-copper(I) complex or copper(II) chelator cuprizone. alpha, beta-methylene ATP increased the amplitude and frequency of contractions in the pregnant uterus, but not affected the contractions in the ovariectomized non-pregnant rat uterus, and neocuproine potentiated this facilitation effect. However, the suppressive effect of neocuproine on the ovariectomized non-pregnant rat uterus increased in the presence of alpha,beta-methylene ATP. Beta-adrenoceptor blocker, propranolol or nitric oxide synthase inhibitor, L-nitroarginine did not affect the responses to neocuproine. These findings suggest that neocuproine can affect the uterus contractile activity by modulation purinergic excitatory responses and that copper(I)-sensitive mechanisms may play a role in this effect.

Effect of phosphodiesterase type 4 inhibitor rolipram on cyclophosphamide-induced cystitis in rats.

Cyclophosphamide induces a severe haemorrhagic cystitis characterized by bladder overactivity. The study was conducted to examine effects of a phosphodiesterase 4 (PDE4) inhibitor rolipram on bladder overactivity in rats with cyclophosphamide treatment. 42 female Wistar rats were used. 30 rats received a single i.p. injection of cyclophosphamide, and after 72 h, bladder function was evaluated by (1) in vitro preparations of whole bladders and (2) cystometry with continuous saline infusion under urethane anesthesia. Cyclophosphamide-treatment dramatically potentiated the basal spontaneous contractions of isolated whole bladders compared to control rats. Atropine, guanethidine or suramin was ineffective on the spontaneous contractions whereas nifedipine completely abolished. Rolipram (5-80 microM) induced a significant concentration-dependent decrease on the amplitude, frequency (contractions/min) and area under the curve of spontaneous contractions. Carbachol elicited phasic contractions superimposed on a tonic contraction. Rolipram caused a relaxation on the tonic contraction whereas it could not affect the phasic contractions induced by carbachol. In anesthetized rats, during continuous infusion cystometry, intercontraction interval was significantly shorter in cyclophosphamide-injected rats than in control rats. Rolipram at 5-40 microM has no significant effect on the intercontraction interval and contraction pressure while it significantly decreased pressure threshold. At 80 microM, it significantly decreased the intercontraction interval and contraction pressure. In conclusion, PDE4 inhibitor rolipram caused a significant decrease on the amplitude, frequency and area under the curve of basal spontaneous contractions in cyclophosphamide-treated rats, at doses that have no effect on the carbachol-induced phasic contractions and cystometric parameters. PDE4 inhibitors may be considered as an attractive strategy for the treatment of cyclophosphamide-induced bladder overactivity.