Amplitude Of Uterine Contractions Research Articles

The Role of TRPV4 Cation Channels in Smooth Muscle Contractile Activity in Rats

Although it was shown that transient receptor potential channels are expressed in the intestinal and myometrial smooth muscle cells and can control gastrointestinal motility and regulate uterine contractility the specific role of transient receptor potential vanilloid-type 4 channel in smooth muscle cells contraction remain largely unknown. The purpose of the study was to test the action of transient receptor potential vanilloid-type 4 selective agonist GSK1016790A on smooth muscle cells contraction in rat’s colon with experimental Parkinson`s disease and in the pregnant rat uterus (18-22 days of gestation). Material and methods. The Parkinson’s disease was induced by single unilateral stereotaxic injection of 12 μg 6-OHDA. The percentage of destroyed dopaminergic neurons was evaluated in apomorphine test (0.5 mg/kg, i.p.) at 1 and 2 weeks after surgery. The water content in faeces was evaluated on the 1st day, then at the 3rd week and 7th month of the experiment. The daily volume of water consumption and gastrointestinal transit time were evaluated at the 3rd week and 7th month after surgery. The action of transient receptor potential vanilloid-type 4 agonist GSK1016790A (0.3 mmol) on smooth muscle cells of colon and myometrium strips contraction was estimated by isometric tension recording. Results and discussion. The apomorphine test showed a progressive increase in the number of turns between the 1st and 2nd week after inducing 6-OHDA-PD. The water content in faeces was increased at the 3rd week (P<0.05) vs. 1st day of the experiment. The rats with 6-OHDA-PD drank less water vs. placebo and intact groups. We observed a 17% delayed GI transit time in 6-OHDA-PD rats (P<0.01) vs. intact and 21% vs. sham-lesioned group of rats 3 weeks after the 6-OHDA treatment. 7 months after the surgery GI transit time was increased more than twice in all studied groups. Transient receptor potential vanilloid-type 4 agonist action on smooth muscle cells of 6-OHDA-PD rats was reduced by 21% compared to intact group and by 46% in sham-lesioned group (P<0.05). After the application of GSK1016790A the rat myometrium strips a 28.4% (P<0.05) decrease of the contractile force was recorded. It was accompanied by a 30.7% (P<0.05) decline of the muscle work estimated as the area under the contractile curve. Suppression of the amplitude of uterine contraction was also followed by a 39.7% (P<0.05) decline of the rise time constant of peaks but unchanged peak duration at the half maximal amplitude. Conclusion. We conclude that pharmacological activation of transient receptor potential vanilloid-type 4 ion channels by their selective agonist GSK1016790A decreased the contractile activity of both colon smooth muscle cells in Parkinson’s disease rats’ model and the myometrium in pregnant rats

Salvia sclarea L. Essential Oil Extract and Its Antioxidative Phytochemical Sclareol Inhibit Oxytocin-Induced Uterine Hypercontraction Dysmenorrhea Model by Inhibiting the Ca2+-MLCK-MLC20 Signaling Cascade: An Ex Vivo and In Vivo Study.

Salvia sclarea essential oil is used as an aromatic therapy for dysmenorrhea. Sclareol—one of the natural products isolated from S. sclarea—displays anti-inflammatory and antioxidant activities; however, researchers have not yet evaluated the mechanism related to the pain-relieving effect of sclareol. In the present study, we aimed to investigate the potential effect of sclareol in ex vivo and in vivo dysmenorrhea models, as well as its possible mechanism. In the ex vivo study of uterine tissue from Sprague Dawley (SD) rats, the uterine contraction amplitude was observed and recorded. In the in vivo study, we measured the uterine contraction pressure of SD rats and performed writhing tests on mice. The uterine tissues from the writhing test subjects were collected and analyzed by Western blot. The results demonstrated that sclareol inhibited prostaglandin (PG) F2α-, oxytocin-, acetylcholine-, carbachol-, KCl-, and Bay K 8644-induced uterine contraction and possessed an analgesic effect in the writhing test. Sclareol affects the Ca2+ level and regulates oxytocin receptor (OTR), myosin light chain kinase (MLCK), extracellular signal-regulated kinase, p-p38, cyclooxygenase-2 (COX-2), and phospho-myosin light chain 20 (p-MLC20) protein expression. Integrating these results, we suggest that sclareol is a potential alternative supplement for dysmenorrhea.

Assessment of uterine activity during IVF by quantitative ultrasound imaging: a pilot study

Research questionDoes uterine activity differ in patients who have undergone successful IVF treatment compared with patients who have undergone unsuccessful IVF treatment? DesignProspective study of 16 women who underwent fresh single embryo transfer. All patients underwent transvaginal ultrasound in three phases of the IVF treatment: ovarian stimulation 1 h before embryo transfer (ET1) and 5–7 days after embryo transfer (ET5–7). Uterine motion analysis was implemented by a dedicated speckle tracking algorithm; frequency- and amplitude-related features were extracted from the derived signals to characterize the uterine activity in relation to ongoing implantation (positive HCG after 6 weeks) and ongoing pregnancy at 11 weeks. ResultsUterine activity in terms of frequency (ovarian stimulation ET1, P = 0.04; ovarian stimulation ET5–7, P = 0.002) and amplitude (ovarian stimulation ET1, P = 0.0003; ovarian stimulation ET5–7, P = 0.000008) is significantly higher in the ovarian stimulation phase compared with ET1 and ET5–7. Women with ongoing pregnancies showed significantly higher uterine contraction frequency compared with those with no ongoing pregnancies in all phases (ovarian stimulation, P = 0.006; ET1, P = 0.015; ET5–7, P = 0.007). Uterine contraction amplitude was significantly lower (P = 0.037) in women at ET5–7 in women with ongoing pregnancies. ConclusionsThis study is a first step towards assessing uterine activity during IVF objectively and non-invasively. It is an essential step to understanding the previously suggested effect of contractions on IVF failure. Uterine activity after embryo transfer characterized by high frequency and low amplitude may favour embryo implantation. Research with larger patient cohorts is needed to build on current evidence and knowledge of uterine contractions during IVF.

Effect of gasotransmitter H2S on adrenergic and cholinergic modulated spontaneous uterine contractions

Abstract Background: Hydrogen sulfide (H2S) is recognized as a gaseous transmitter in mammalian tissues. Several physiological roles for H2S including vasodilation, and smooth muscle relaxation have been documented. The exact mechanism explaining its role in uterine contractility remain to be elucidated. The proposed study was conducted to elucidate H2S role in uterine contractility in relation to adrenergic and cholinergic systems. Methods: Isolated uterus horn of adult virgin female sprage Dawely rats were used in vitro in physiological saline solution, the effects of H2S donor (NaHS), H2S blocker aminooxiacetic acid (AOAA) with or without adrenergic and cholinergic drugs and glibenclamide were determined. Results: It was revealed that, NaHS inhibited myometrial contractions as regard the tone and amplitude, whereas AOAA increased the tone of uterine contractility. The relaxant effect of H2S on uterine contractility was mediated by modulation of the endogenous adrenergic and cholinergic systems in the myometrium, which was demonstrated by dual interaction of NaHS or AOAA with Adrenaline, Propranolol, Prazosin, Acetylcholine and Atropine on the tone, peak, amplitude and frequency of uterine contractions. Glibencalmide (KATP channels blocker) after NaHS significantly increased the tone, peak and amplitude. However Glibencalmide after AOAA produced no significant changes in the tone, peak and amplitude of uterine contractions. Conclusion: H2S has a relaxant action in smooth muscles of myometrium. This inhibitory effect of H2S on uterine contractility could be through dual interaction and modulation of the endogenous adrenergic and cholinergic systems and activation of KATP channels.

Inhibitory effect of Bisphenol A on in vitro feline uterine contractions

Bisphenol A (BPA) is an environmental pollutant used as a plasticizer in the manufacture of many plastic products, such as packaging, containers, and water and beverage bottles. There are deleterious effects of BPA on metabolic, endocrine, nervous, and reproductive systems. This is the first study in which there was investigation of the in vitro effect of BPA on the spontaneous contractions of the cat uterus. The tubal uterine segments (1 cm) collected from queens in estrus were suspended in an isolated organ bath. Following tissue stabilization, spontaneous contractions were recorded for 10 min to constitute the control group. The effects of the solvent (alcohol) and BPA at different concentrations (1, 10, and 100 μM) on uterine contractions were subsequently evaluated at 10 min intervals in terms of frequency and mean amplitude variables. The ethanol vehicle did not alter the uterine contractions compared to the control group. All concentrations of BPA used in the study resulted in a reduction (P < 0.05) in amplitude of uterine contractions in a dose-dependent manner, while only the largest dose of BPA decreased the frequency of contractions (P < 0.05). In reproductive physiology, regular uterine contractions facilitate successful fertilization, migration, implantation, and maintenance of pregnancy, as well as fetus expulsion. The results of this study indicate BPA has an inhibitory effect on spontaneous contractions of the cat uterus. It is proposed that this suppressive effect of BPA on uterine contractions might lead to queen infertility.

An empirical model for educational simulation of cervical dilation in first-stage labor

BackgroundSeveral models for educational simulation of labor and delivery were published in the literature and incorporated into a commercially available training simulator (CAE Healthcare Lucina). However, the engine of this simulator does not include a model for the clinically relevant indicators: uterine contraction amplitude and frequency, and cervical dilation. In this paper, such a model is presented for the primigravida in normal labor.MethodsThe conceptual and mathematical models represent oxytocin release by the hypothalamus, oxytocin pharmacokinetics, and oxytocin effect on uterine contractions, cervical dilation, and (positive) feedback from cervical dilation to oxytocin release by the hypothalamus.ResultsSimulation results for cervical dilation are presented, together with target data for a normal primigravida. Corresponding oxytocin concentrations and amplitude and frequency of uterine contractions are also presented.ConclusionAn original empirical model for educational simulation of oxytocin concentration, uterine contractions, and cervical dilation in first-stage labor is presented. Simulation results for cervical dilation match target data for a normal patient. The model forms a basis for taking into account more independent variables and patient profiles and can thereby considerably expand the range of training scenarios that can be simulated.

Lignocaine augments the in-vitro uterine contractions involving NO-guanylyl cyclase dependent mechanisms

AimsLignocaine is used during intrapartum and postpartum period but there are conflicting reports regarding the effect of lignocaine on uterine contractility. Therefore, this study was undertaken to delineate the effect of lignocaine on uterine contractility and the underlying mechanisms. Main methodsThe in vitro contractions were recorded from the uterine segments obtained from adult rats (in estrous phase) and also from human myometrial tissue. Effect of lignocaine on spontaneous uterine contractions was recorded in the absence or presence of antagonists. Effect of sodium nitroprusside (SNP, NO donor) on uterine contractility was assessed. The NO2− was assayed (indicator of NO activity) from the supernatant after exposing the myometrial tissue to lignocaine in the absence or the presence of L-NAME or hemoglobin. Key findingsLignocaine (100μM) increased the amplitude of uterine contractions by 75% with no alterations in frequency. Similar magnitude of increase was seen with human myometrial tissue also. The spontaneous activities were absent in Ca2+-free or in nifedipine (10μM) containing medium. Heparin (IP3 blocker, 10IU/ml), but not the indomethacin (10μM) blocked the lignocaine-induced augmentation. L-NAME (NOS inhibitor, 10μM) or methylene blue (guanylyl cyclase inhibitor, 100μM) partially blocked the lignocaine-induced augmentation. SNP (30μM) increased the amplitude of spontaneous uterine contractions. Lignocaine increased the NO2− content (indicator of NO activity) of uterine tissue and the increase was blocked by L-NAME or hemoglobin. SignificancePresent observations indicate that lignocaine augments the amplitude of uterine contractions via Ca2+-dependent mechanisms involving NO-G cyclase-dependent mechanisms.

Gebe ratlarda isradipinin uterus kontraksiyonları üzerine inhibitör etkileri

Objective: To investigate the effects of isradipine, which is a calcium channel blocker, on late pregnant rats’ myometrium under in vitro conditions. Methods: Stripes were obtained from the myometriums of pregnant rats which were decapitated on the 18 days of gestation. The effects of isradipine on myometrium were investigated in four groups and four cumulative doses: 1 ng/ml, 10 ng/ml, 0.1 μg/ml, 1 μg/ml. Group 1: spontaneous myometrial contractions, Group II: myometrial contractions induced by oxytocin, Group III: myometrial contractions induced by prostaglandin, Group IV: myometrial contractions induced by oxytocin in calcium-free medium. Wilcoxon signed ranks test was used for the statistical analysis and p<0.05 was considered statistically significant. Results: Group 1: compared to the control group, 10 ng/mL and 0.1 μg/mL isradipine decreased the amplitude of uterine contractions. Group II: 0.1 μg/mL isradipine decreased the frequency of contractions (p=0.02). Isradipine decreased the amplitudes of contractions in the doses of 10 ng/mL and 0.1 μg/mL (p=0.02 for each dose). Group III: 0.1 μg/mL isradipine decreased the frequency of contractions (p=0.02). Isradipine decreased the amplitudes of contractions in the doses of 10 ng/mL and 0.1 μg/mL (p=0.02 for each dose). One μg/mL isradipine completely removed all spontaneous and induced contractions. Group IV: when compared to mediums with calcium, both amplitudes and frequencies of the contractions were found lower in this group (p<0.001). Isradipine was only used in the dose of 1 μg/mL and it completely removed all contractions.

A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes

Traditionally, pregnancy was considered to have a positive effect on endometriosis and its painful symptoms due not only to blockage of ovulation preventing bleeding of endometriotic tissue but also to different metabolic, hormonal, immune and angiogenesis changes related to pregnancy. However, a growing literature is emerging on the role of endometriosis in affecting the development of pregnancy and its outcomes and also on the impact of pregnancy on endometriosis. The present article aims to underline the difficulty in diagnosing endometriotic lesions during pregnancy and discuss the options for the treatment of decidualized endometriosis in relation to imaging and symptomatology; to describe all the possible acute complications of pregnancy caused by pre-existing endometriosis and evaluate potential treatments of these complications; to assess whether endometriosis affects pregnancy outcome and hypothesize mechanisms to explain the underlying relationships. This systematic review is based on material searched and obtained via Pubmed and Medline between January 1950 and March 2015. Peer-reviewed, English-language journal articles examining the impact of endometriosis on pregnancy and vice versa were included in this article. Changes of the endometriotic lesions may occur during pregnancy caused by the modifications of the hormonal milieu, posing a clinical dilemma due to their atypical appearance. The management of these events is actually challenging as only few cases have been described and the review of available literature evidenced a lack of formal estimates of their incidence. Acute complications of endometriosis during pregnancy, such as spontaneous hemoperitoneum, bowel and ovarian complications, represent rare but life-threatening conditions that require, in most of the cases, surgical operations to be managed. Due to the unpredictability of these complications, no specific recommendation for additional interventions to the routinely monitoring of pregnancy of women with known history of endometriosis is advisable. Even if the results of the published studies are controversial, some evidence is suggestive of an association of endometriosis with spontaneous miscarriage, preterm birth and small for gestational age babies. A correlation of endometriosis with placenta previa (odds ratio from 1.67 to 15.1 according to various studies) has been demonstrated, possibly linked to the abnormal frequency and amplitude of uterine contractions observed in women affected. Finally, there is no evidence that prophylactic surgery would prevent the negative impact of endometriosis itself on pregnancy outcome. Complications of endometriosis during pregnancy are rare and there is no evidence that the disease has a major detrimental effect on pregnancy outcome. Therefore, pregnant women with endometriosis can be reassured on the course of their pregnancies although the physicians should be aware of the potential increased risk of placenta previa. Current evidence does not support any modification of conventional monitoring of pregnancy in patients with endometriosis.

Combining Sprague–Dawley rat uterus cell membrane chromatography with HPLC/MS to screen active components from Leonurus artemisia

Context: Leonurus artemisia (Lour.) S.Y.Hu (Lamiaceae) (YiMuCao in Chinese) is a traditional Chinese medicine. Leonurus artemisia has been shown to have many pharmacological effects such as increasing uterine contraction amplitude, and tension, but the active components are still unknown.Objective: The objective of this study is to determine active components of L. Artemisia that are responsible for the biological activity using HPLC and cell membrane-based system.Materials and methods: The whole L. artemisia ethanol extract and its eight fractions were screened using Sprague–Dawley rat uterus cell membrane chromatography (CMC) combined with the HPLC/MS system. Oxytocin was used to investigate the activity of CMC column. The effect of active components screened from L. artemisia was studied by tension measurement of isolated rat uterine strips in vitro at a dose of 10−7–10−4 mol/L with oxytocin as a control.Results: The acetone extract showed obvious activity when compared with the eight extracts of L. artemisia. From the acetone extract, in the negative ionization mode, the active compound was identified as genkwanin, with a molecular weight of 283. In vitro pharmacological experiments proved that genkwanin promoted uterine contractions at a dose from 10−7 to 10−4 mol/L. The EC50 value was 4.86 ± 4.21 μmol/L for genkwanin and 4.30 ± 3.65 μmol/L for oxytocin on the contractile amplitude of uterine strips isolated from rats.Discussion and conclusion: Genkwanin was identified as the active compound in L. artemisia by this method. In vitro pharmacological experiments proved that genkwanin promoted uterine contractions. Genkwanin may be used to uterine inertia and may have an effect on postpartum hemorrhage.

Computational modeling reveals key contributions of KCNQ and hERG currents to the malleability of uterine action potentials underpinning labor.

The electrical excitability of uterine smooth muscle cells is a key determinant of the contraction of the organ during labor and is manifested by spontaneous, periodic action potentials (APs). Near the end of term, APs vary in shape and size reflecting an ability to change the frequency, duration and amplitude of uterine contractions. A recent mathematical model quantified several ionic features of the electrical excitability in uterine smooth muscle cells. It replicated many of the experimentally recorded uterine AP configurations but its limitations were evident when trying to simulate the long-duration bursting APs characteristic of labor. A computational parameter search suggested that delayed rectifying K+ currents could be a key model component requiring improvement to produce the longer-lasting bursting APs. Of the delayed rectifying K+ currents family it is of interest that KCNQ and hERG channels have been reported to be gestationally regulated in the uterus. These currents exhibit features similar to the broadly defined uterine I K1 of the original mathematical model. We thus formulated new quantitative descriptions for several I KCNQ and I hERG. Incorporation of these currents into the uterine cell model enabled simulations of the long-lasting bursting APs. Moreover, we used this modified model to simulate the effects of different contributions of I KCNQ and I hERG on AP form. Our findings suggest that the alterations in expression of hERG and KCNQ channels can potentially provide a mechanism for fine tuning of AP forms that lends a malleability for changing between plateau-like and long-lasting bursting-type APs as uterine cells prepare for parturition.

The leaves of Ficus exasperata Vahl (Moraceae) generates uterine active chemical constituents

Ethnopharmacological RelevanceIn the search for new, safe and efficacious uterine active agents, the plant Ficus exasperata was subjected to phytochemical screening and pharmacological analysis. Materials and methodsEthyl acetate and methanolic leaf extracts of Ficus exasperata were fractionated and purified by a series of chromatographic techniques. The isolation process was guided by in vitro functional uterine assays involving the use of C57Bl/6 female mice. Identification of the active chemical constituents was performed by several spectroscopic techniques which included 1D and 2D nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS). The uterine effects of these compounds were investigated on spontaneous, oxytocin-induced and high KCl-induced contractions using isolated uterine segments of non-pregnant female mice. The activity of different compounds on the amplitude (maximum tension above basal force) and frequency of uterine contractions were simultaneously measured and then statistically analysed. The structure–activity relationships were also examined where possible. ResultsThese studies led to the identification of some new phytochemical derivatives. Pharmacological assay revealed the presence of both uterine stimulatory and inhibitory constituents. The new pheophytin/pheophorbide derivatives, flavonoids, fatty acids and glycerol derivatives significantly reduced the frequency and amplitude of uterine contraction, while KCl salt, pyrimidine and pheophorbide-b derivatives significantly augmented both spontaneous and agonist-induced contractions. ConclusionThis study has demonstrated that Ficus exasperata generates secondary metabolites which have proven effective in the significant inhibition of uterine contractions and thus a potential source of new tocolytic agents. Additionally, uterine stimulatory constituents were also generated some of which may be potential drugs for contraception and/or labour facilitation. Lead compounds generated from this study are the pheophytin/pheophorbide derivatives, pyrimidine derivatives and flavonoid derivatives.

Inhibitory effects of aqueous extract of Hibiscus sabdariffa on contractility of the rat bladder and uterus

We examined an aqueous extract of Hibiscus sabdariffa calyces extracts (HSE) by close-arterial injection on micturition thresholds (MTs) and on uterine contractions (rate and amplitude). Five doses of HSE were examined (1, 5, 10, 50, and 100 mg/kg) in 3 groups of rats: controls, after bladder inflammation, and after bilateral hypogastric neurectomy. In some rats, uterine contractions were induced by injection of oxytocin (OT) and the effect of HSE was compared with that of nifedipine. HSE increased MTs in a dose-dependent manner in all groups. Neither atropine (0.1 mg/kg) nor propranolol (0.4 mg/kg) had significant effects on cystometric parameters. They also did not affect the responses obtained by HSE on cystometric parameters. As with bladder response, HSE inhibited both the rate and amplitude of uterine contractions in all groups in a dose-dependent manner. The uterine response to HSE was not affected by administration of either atropine or propranolol. A slight, but significant, reduction of contraction amplitude by HSE in the OT precontracted uteri was only noted at a dose of 500 mg/kg. Nifedipine was more potent than HSE in reducing uterine contraction amplitude. The present work documents inhibition by HSE of the rat bladder and uterine contractility in a dose-dependent manner via a mechanism unrelated to local or remote autonomic receptors or calcium channels. However, further investigation is needed to establish the exact mechanism of action.

Term-dependency of P2 receptor-mediated contractile responses of isolated human pregnant uterus

Objective The aim of the study was to test the hypothesis that in the human uterus, the effectiveness of P2 receptor-mediated contractile responses is up-regulated during pregnancy. Study design Experiments were performed on myometrial samples obtained from women undergoing caesarean section at 28–30 weeks of pregnancy (3 women, Group 1), 32–34 weeks of pregnancy (6 women, Group 2) and 38–41 weeks of pregnancy (16 women, Group 3). Concentration–response relationships for a non-selective P2 receptor agonist, adenosine 5′-triphosphate (ATP), a selective P2X receptor agonist, α,β-methylene-ATP (α,β-meATP), and a frequency–response relationship for non-adrenergic non-cholinergic (NANC) electrical field stimulation (EFS) were obtained using routine pharmacological organ bath technique. Effects of pyridoxalphosphate azophenyl-2′,4′-disulphonic acid (PPADS, 10 −5 M), a P2 receptor antagonist, were also evaluated. Parametric Student's t-test, non-parametric Wilcoxon T-test, Mann–Whitney U-test, two-way analysis of variance (ANOVA) and Krushkal–Wallis tests were used for statistical analysis. Results ATP (10 −6 to 3 × 10 −4 M), α,β-meATP (10 −7 to 3 × 10 −5 M) and EFS (2–32 Hz) evoked contractions of isolated pregnant uterus in all three groups. Uterus responses to ATP were not correlated with the term of pregnancy while the amplitude of uterine contractions to α,β-meATP and EFS was higher in full term pregnancy than in earlier pregnancy. PPADS antagonized uterus responses to α,β-meATP and EFS, but not to ATP, in all three groups. Conclusion P2X receptor-mediated contractions of human pregnant uterus to α,β-meATP and EFS, but not to ATP, are increased with the progression of pregnancy.

Possible neural mediation of the central effects of oxytocin on uterine motility

The central nervous system contains the nuclei at the origin of autonomic and neuroendocrine pathways to the uterus. Although the anatomical basis of these pathways is known, the conditions of their recruitment and their interactions in the context of copulation remain to be explored. We tested the hypothesis that some central mechanisms could simultaneously recruit both pathways to the uterus. In this aim, we recorded intrauterine pressure changes in anesthetized female rats at the estrus stage after intracerebroventricular (ICV) administration of oxytocin (OT). Doses of 0.3-300 ng elicited increases of frequency and amplitude of uterine contractions. These effects were partly mimicked by the OT agonist [Thr(4),Gly(7)]OT but not by arginine vasopressin. They were blocked by the OT receptor antagonist atosiban delivered either ICV or intravenously. The latter suggests that ICV OT activated the systemic release of OT. The effects of OT were also blocked by hexamethonium, a ganglionic blocking agent, by atropine, a muscarinic receptor antagonist, and by N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis. The results reveal that ICV OT recruits autonomic efferent pathways to the uterus. These results support our hypothesis that the activation of central nuclei can promote uterine contractility, and that OT may be a central coordinator of autonomic and neuroendocrine pathways. The hypothalamus, the source of direct OT-ergic projections to the pituitary, the brain stem, and the spinal cord, may be a target of central OT.

Uterine contractility and directed sperm transport assessed by hysterosalpingoscintigraphy (HSSG) and intrauterine pressure (IUP) measurement.

Uterine peristalsis sustains sperm transport and can be detected by hysterosalpingoscintigraphy (HSSG). This study is the first to be designed to investigate utero-tubal transport function by HSSG and uterine contractility by intrauterine pressure measurement (IUP) consecutively on the same day in the periovulatory phase. Twenty-one female subjects (mean age 28.4 years) without a gynecologic history were examined sequentially by HSSG and IUP on the same day to evaluate uterine contractility in relation to the utero-tubal transport function. In HSSG, intact transport function was visualized by the rapid uptake of 99m-technetium-marked albumin aggregates through the female genital tract. In IUP, the frequency of uterine contractions (UC/min), amplitude of uterine contractions and basal pressure tone were detected via a intrauterine catheter. HSSG and IUP were embedded in cycle monitoring with measurement of LH and estradiol. In HSSG, a positive transport of inert particles was assessed in 20 of 21 subjects, in 76% to the side of the dominant follicle or on both sides of the oviduct, and in 19% a strict contralateral transport could be observed. In only one subject (5%), no transport was assessed. The mean value of uterine contractions was 3.4 UC/min (SD +/- 0.7), the mean amplitude was 12.0 mmHg (SD +/- 4.25 mmHg). Basal pressure tone was 70.7 mmHg. There was a statistically significant correlation with estradiol levels: none of the subjects with less than 3 UC/min showed an estradiol level higher than 100 pg/mL; nearly every patient (one exception) with more than 3 UC/min had an estradiol level higher than 100 pg/mL (p < 0.0001, Fisher's exact test). Intact periovulatory utero-tubal transport function can be documented by HSSG and is caused by directed uterine contractility, measured consecutively by IUP. Uterine contractility is influenced by rising estradiol levels. Directed uterine contractility and intact utero-tubal transport function are considered necessary for intact sperm transport, mainly to the side bearing the dominant follicle to maximize fertility.

Role of Capsaicin-Sensitive Nerve Fibers in Uterine Contractility in the Rat1

The possible participation of capsaicin-sensitive sensory nerves in the modulation of neurogenic contractions was studied in nonpregnant and term pregnant rat uteri. Neurogenic contractions were elicited by electric field stimulation (40 V, 1-70 Hz, 0.6 msec) in intact uteri and uteri that were previously exposed to capsaicin in vitro. In capsaicin pretreated preparations obtained both from nonpregnant and term pregnant rats, a dose-dependent increase in the amplitude of uterine contractions was detected. Prior systemic treatment of the rats with capsaicin (130 mg/kg, s.c.) abolished the effect of in vitro capsaicin administration on the amplitude of neurogenic contractions. Use of a specific antagonist of calcitonin gene-related peptide revealed that depletion of this peptide, which normally elicits uterine smooth muscle relaxation, may be responsible for the increased responsiveness of the uterus to low-frequency stimulation. Experiments on the localization of calcitonin gene-related peptide in uterine tissue specimens exposed to capsaicin revealed dose-dependent depletion of calcitonin-gene related peptide-immunoreactive nerves innervating blood vessels and the myometrium. The findings indicate that capsaicin-sensitive afferent nerves, by the release of sensory neuropeptides, significantly contribute to the modulation of uterine contractility both in nonpregnant and term pregnant rats. It is suggested that uterine sensory nerve activation may be part of a trigger mechanism leading to preterm contractions evoked by, for example, inflammation.

Uterine contractility and directed sperm transport assessed by hysterosalpingoscintigraphy (HSSG) and intrauterine pressure (IUP) measurement

Background. Uterine peristalsis sustains sperm transport and can be detected by hysterosalpingoscintigraphy (HSSG). This study is the first to be designed to investigate utero-tubal transport function by HSSG and uterine contractility by intrauterine pressure measurement (IUP) consecutively on the same day in the periovulatory phase. Methods. Twenty-one female subjects (mean age 28.4 years) without a gynecologic history were examined sequentially by HSSG and IUP on the same day to evaluate uterine contractility in relation to the utero-tubal transport function. In HSSG, intact transport function was visualized by the rapid uptake of 99m-technetium-marked albumin aggregates through the female genital tract. In IUP, the frequency of uterine contractions (UC/min), amplitude of uterine contractions and basal pressure tone were detected via a intrauterine catheter. HSSG and IUP were embedded in cycle monitoring with measurement of LH and estradiol. Results. In HSSG, a positive transport of inert particles was assessed in 20 of 21 subjects, in 76% to the side of the dominant follicle or on both sides of the oviduct, and in 19% a strict contralateral transport could be observed. In only one subject (5%), no transport was assessed. The mean value of uterine contractions was 3.4 UC/min (SD ± 0.7), the mean amplitude was 12.0 mmHg (SD ± 4.25 mmHg). Basal pressure tone was 70.7 mmHg. There was a statistically significant correlation with estradiol levels: none of the subjects with less than 3 UC/min showed an estradiol level higher than 100 pg/mL; nearly every patient (one exception) with more than 3 UC/min had an estradiol level higher than 100 pg/mL (p < 0.0001, Fisher's exact test). Conclusions. Intact periovulatory utero-tubal transport function can be documented by HSSG and is caused by directed uterine contractility, measured consecutively by IUP. Uterine contractility is influenced by rising estradiol levels. Directed uterine contractility and intact utero-tubal transport function are considered necessary for intact sperm transport, mainly to the side bearing the dominant follicle to maximize fertility.

Contrasting effects of WIN 55212-2 on motility of the rat bladder and uterus.

Both the uterus and bladder contain cannabinoid (CB) receptors whose functions are poorly understood. Here, in urethane-anesthetized female rats in metestrus, we simultaneously compared the effects of close-arterial injections of the cannabinoid receptor agonist WIN 55,212-2 (WIN2) on uterine contractions (amplitude and rate) and micturition thresholds (MT) assessed by cystometry. Five doses of WIN2 were delivered (0.01, 0.1, 0.5, 1, and 1.5 micromol/kg) in three groups: (1) controls; (2) after bladder inflammation with intravesicular turpentine; and (3) after bilateral hypogastric neurectomy (HYPX). In some rats, drugs were delivered via the tail vein. Regarding bladder, WIN2 dose-dependently reduced MTs in all groups. Both bladder inflammation and HYPX significantly increased this effect. Regarding uterus, WIN2 dose-dependently increased uterine contraction amplitude. Bladder inflammation or HYPX significantly decreased this effect. Coinjection of the CB1 antagonist SR141716A (SR) (1.5 micromol/kg) and WIN2 (0.5 micromol/kg) abolished or reduced the effects of WIN2 in both organs. SR alone had significant effects only after HYPX, reducing both MT and uterine contraction amplitude. The vehicle (0.4% DMSO) and inactive enantiomer S(-)-WIN 55,212-3 were both ineffective. Close-arterial injections of WIN2 (0.5 micromol/kg) produced significantly larger effects in both organs than tail vein injections. These results indicate that, whereas WIN2 reduces bladder motility, it mainly increases uterine motility, likely via CB1 receptors located in the two organs. The opposing effects of bladder inflammation and HYPX on the potency of WIN in the two organs suggest a neurally mediated viscero-visceral interaction in which bladder inflammation influences uterine CB1 sensitivity, possibly by inhibiting adrenergic input to the uterus.

Contrasting Effects of WIN 55212–2 on Motility of the Rat Bladder and Uterus

Both the uterus and bladder contain cannabinoid (CB) receptors whose functions are poorly understood. Here, in urethane-anesthetized female rats in metestrus, we simultaneously compared the effects of close-arterial injections of the cannabinoid receptor agonist WIN 55,212–2 (WIN2) on uterine contractions (amplitude and rate) and micturition thresholds (MT) assessed by cystometry. Five doses of WIN2 were delivered (0.01, 0.1, 0.5, 1, and 1.5 μmol/kg) in three groups: (1) controls; (2) after bladder inflammation with intravesicular turpentine; and (3) after bilateral hypogastric neurectomy (HYPX). In some rats, drugs were delivered via the tail vein. Regarding bladder, WIN2 dose-dependently reduced MTs in all groups. Both bladder inflammation and HYPX significantly increased this effect. Regarding uterus, WIN2 dose-dependently increased uterine contraction amplitude. Bladder inflammation or HYPX significantly decreased this effect. Coinjection of the CB1 antagonist SR141716A (SR) (1.5 μmol/kg) and WIN2 (0.5 μmol/kg) abolished or reduced the effects of WIN2 in both organs. SR alone had significant effects only after HYPX, reducing both MT and uterine contraction amplitude. The vehicle (0.4% DMSO) and inactive enantiomerS(−)-WIN 55,212–3 were both ineffective. Close-arterial injections of WIN2 (0.5 μmol/kg) produced significantly larger effects in both organs than tail vein injections. These results indicate that, whereas WIN2 reduces bladder motility, it mainly increases uterine motility, likely via CB1 receptors located in the two organs. The opposing effects of bladder inflammation and HYPX on the potency of WIN in the two organs suggest a neurally mediated viscero-visceral interaction in which bladder inflammation influences uterine CB1 sensitivity, possibly by inhibiting adrenergic input to the uterus.