Interaction between oxytocin and 'sidaverin' on the gravid and non-gravid rat uterus

Sidaverin, a crystalline compound extracted from a polar fraction of Sida veronicaefolia (Lam), elicited oxytocin-like contractions in the non-gravid rat isolated uterus preparation with a concentration-response relationship. Equipotent concentrations of oxytocin and sidaverin, using matched responses, were approximately 0.16 U and 0.4 micrograms ml-1, respectively. Sidaverin-induced contractile response was atropine reversible. The concentration-response curves for sidaverin and oxytocin were parallel, and both responses were inhibited by the specific oxytocin antagonist, Atosiban, indicating possible involvement of oxytocin receptors in the action of sidaverin. There were potentiation of action of one drug to that of the other, irrespective of the order of administration and even after washing off the first before introducing the second drug. In the gravid uterus, sidaverin produced contractions in preparations from day 1 to day 6 or 7, caused relaxation in days 7-11, and elicited contractions in day 11 through term, the sensitivity of the preparations increasing exponentially toward term with strong sustained contractions. With the exception of days 7-11, when sidaverin antagonized oxytocin action, it potentiated action of oxytocin on the gravid uterus.     

Nitric oxide synthase activity in the gravid rat uterus decreases a day before the onset of parturition

OBJECTIVE: Our purpose was to determine the timing, tissue location, and isoform of the uterine nitric oxide synthase activity decrease at term in gravid rat uteri. STUDY DESIGN: Nitric oxide synthase specific activity was assayed in rat uteri 11 through 22 days' gestation by the difference in radiolabeled arginine to citrulline conversion with and without the cofactor reduced nicotinamide adenine dinucleotide phosphate. Nitric oxide synthase isoform was assessed by calcium sensitivity and subcellular location. RESULTS: Rat uterine nitric oxide synthase activity decreased between days 15 and 21 of gestation but did not decrease further at term (day 22), before and after the onset of labor. Decidual nitric oxide synthase activity exceeded the myometrial activity at 15 days' gestation, but then the two were equal at 18 through 22 days' gestation. The nitric oxide synthase activity was calcium insensitive except for half the decidual cytosolic activity on day 15. CONCLUSION: The decrease in pregnant rat uterine nitric oxide synthase activity coincides with the preparation of the uterus for parturition rather than the final activation of labor.     

Sacculation and retroversion of the gravid uterus in the third trimester

Primary retroperitoneal mucinous cystic tumors are extremely rare, and although their histogenesis is still uncertain, several theories have been proposed. Traditionally, transabdominal laparotomy and enucleation of the cyst is the treatment of choice and laparoscopic resection has not previously been reported. This paper presents the case of a 48-year-old woman in whom a primary retroperitoneal cystic mass, 15 x 13 x 9 cm in size, was successfully resected through the laparoscope. Pathological examination revealed a mucinous cystadenoma with borderline malignancy. The patient had a prompt recovery and there was no evidence of recurrence at her 8-month follow-up. However, the prevention of cystic fluid spillage during laparoscopic manipulation is important, especially when the pathology of the retroperitoneal cyst is unclear.     

Ultrastructure of the gravid uterus of Hymenolepis diminuta (Platyhelminthes: Cestoda)

The fine structure of the uterus in gravid proglottids of Hymenolepis diminuta was examined by standard techniques for scanning and transmission electron microscopy. The uterus consisted of a syncytial uterine epithelium attached to the medullary parenchyma through a thin extracellular basal matrix. The epithelium contained prominent nuclei in the juxtalumenal cytoplasm. The cytoplasm was dominated by extensive granular endoplasmic reticulum, with dilated cisternae containing an electron-lucent material and widely scattered electron-dense spherical bodies. No Golgi body or other agranular endomembrane component was observed, but the epithelium contained numerous free ribosomes and a few mitochondria. The apical plasma membrane was folded into long microlamellae. Epithelial and epitheliomesenchymal folds and villi resulted in a compartmentalized uterine lumen, with each chamber containing 1 to several eggs. These data suggest a high level of synthetic activity within the uterine epithelium, but the chemical products and functional significance of this activity are not yet known.     

The effect of ageing on the histochemically demonstrable catecholamines in the hypogastric (main pelvic) ganglion of the rat

The effect of ageing on adrenergic neurons was studied in the hypogastric ganglion of the male rat using the formaldehyde-induced fluorescence method. With age, two changes were obvious. Firstly, the fluorescence intensity of the neurons decreased throughout postnatal life and the number of completely non-fluorescent adrenergic neurons increased. Secondly, the amount of non-specific fluorescence due to lipofuscin pigment increased. The pigment fluorescence was also found around the neurons in satellite cells.     

The effect of local chemical sympathectomy of the rat uterus on its sensitivity to sex hormones

Chemical sympathectomy of the rat uterus did not alter the main metabolic processes maintaining the uterus weight even though it changed its response to sex steroids. Sensitivity of endo- and myometrium to progesterone significantly decreased thus inducing a relative increase in the estradiol action.     

Cholinergic receptors in the rat uterus

Natural anti-tumor antibodies (NAA) were revealed, by a complement-dependent cytotoxicity test on el4 lymphoma cells, in the serum of C3Hf but not of C57BL mice. Hybrids between the positive C3Hf and the negative C57Bl mice were NAA producers. Individual variability of NAA level was found in C3Hf and in the hybrids. The study of mice housed in the same or in different cages and of mice belonging to the same or to different litters demonstrated a randomly distributed variability. These observations seem to exclude environmental influences on the natural immune response or genetic mutations in the C3Hf strain with the appearance of variants with different NAA content. The NAA level was age-dependent with a peak around 20-24 weeks of age. Inoculum of lymphoma cells induced an increase in the NAA level both in C3Hf and in the hybrids but not in C57Bl mice which seem therefore incapable of making guinea-pig complement-fixing NAA. The individual variability of NAA level and the stimulating effect of tumor cells support a potential role of NAA in immunosurveillance of oncogenesis.     

Protein requirements of sheep in late pregnancy: partitioning of nitrogen between gravid uterus and maternal tissues

The objective of this study was to quantify effects of maternal protein nutrition on N accretion or loss in conceptus and maternal tissues of ewes during late pregnancy. Ewes, pregnant with twins, were fed low (LP, 79 g CP/kg DM), medium (MP, 116 g CP/kg DM), or high (HP, 157 g CP/kg DM) protein diets, each with an estimated ME concentration of 2.7 Mcal/kg DM, between d 111 and 140 of pregnancy; all ewes had been fed the same diet (2.7 Mcal ME, 120 g CP/kg DM) for the previous 30 d (d 80 to 110). Dry matter intakes were varied (LP = 1.0, MP = 1.2, and HP = 1.4 kg/d) according to predicted energy costs of protein deposition for each diet. Nitrogen accretion was estimated by comparative slaughter (d 140 minus d 110) and by collection of excreta between d 120 and 130. Fresh weights of maternal and gravid uterine tissues were measured at slaughter, before proximate analysis of these components. Whole-body N retention was directly and linearly related to N intake, but efficiency of deposition of apparently absorbed N decreased linearly with increasing N intake (LP, .79; MP, .70; HP, .62). Nitrogen accretion in the gravid uterus, maternal viscera, and mammary gland was significantly less in LP than in MP or HP ewes. Nitrogen balance in maternal carcass tissues was linearly related to N intake, ranging from a negative value in LP ewes to a positive value in HP ewes (LP, -63 g; MP -39 g; HP, 55 g). These data provide the basis for estimating N requirements for protein accretion in the conceptus and in maternal tissues during late pregnancy. They also highlight the capacity of maternal carcass tissues to mobilize or deposit amino acids in response to variations in dietary protein supply.     

Unspecific binding capacity of androgen receptors in the rat uterus

Plasma levels of cAMP and serum concentrations of IgE have been determined in children with acute atopic dermatitis (AD) and in a healthy control group, to illuminate the pathophysiological mechanisms that cause AD. There were significantly lower plasma levels of cAMP (P < 0.001) and significantly higher levels of serum IgE (P < 0.004) in children with AD, in comparison with a healthy control group. It is possible that defective control of c-AMP levels could contribute to the immunopathogenesis of AD and monitoring levels may be of value in the clinical evaluation of the disease.     

The effects of oxytocin on the pattern of electrical propagation in the isolated pregnant uterus of the rat

Prior work from mammals suggests that load experienced by extensor muscles of the hindlimbs (i.e. Duysens and Pearson 1980; Pearson and Collins 1993; Fouad and Pearson 1997) or cutaneous afferents from the plantar surface of the foot (Duysens and Pearson 1976; Guertin et al. 1995) enhances activity in extensor muscles during the stance phase, and delays the onset of flexor activity associated with the swing phase. The presumed functional significance of this phenomenon is that extensor activity of the supporting limb during walking can: (a) reinforce the supporting function in proportion to the load experienced, and (b) prolong the stance phase until unloading of the limb has occurred. Whether a similar functional role exists for load-sensitive afferents during walking in the human is unknown. In this study, the effect of adding or removing a substantial load (30% of body weight) at the centre of mass was studied in healthy adult human subjects. Loads were applied near the centre of mass to avoid the need for postural adjustments which might confound the interpretation of the results. Subjects walked on a treadmill with either: (a) a sustained increase or decrease in load, or (b) a sudden unexpected increase or decrease in load. In general, subjects responded to the changes in load by changing the amplitude of the extensor electromyographic (EMG) bursts. For example, with sudden unexpected additions in load, the average increase in amplitude was 40% for the soleus across the stance phase, and 134% for the quadriceps during the early part of the stance phase. Extensor EMGs increased with both sustained and sudden increases in load. Extensor EMG durations also increased (average increase in duration of 4% for soleus with sudden loading, and 7% for sustained loading). Cycle duration hardly changed (average increase of 0.5% with both sudden and sustained loading). These results differ from those of infants subjected to a similar perturbation during supported walking. A large change in timing (i.e. an increase in the duration of the stance phase by 30% and the step cycle by 28%) was seen in the infants, with no change in the amplitude of the EMG burst (Yang et al. 1998). These results suggest that the central nervous system can control the timing and amplitude of extensor EMG activity in response to loading independently. Maturation of the two components most likely occurs independently. In the adult, independent control of the two components may provide greater flexibility of the response.     

Acute effects of catecholamines on function of the rat right heart

OBJECTIVE: Although the haemodynamic effects of catecholamines on the rat left ventricle have been investigated extensively, only few systematic in vivo studies have been performed on the right ventricle. The aim was to examine the acute effects of noradrenaline and isoproterenol on rat right ventricular function. METHODS: Haemodynamic variables were measured during acute, 20 minute infusion of noradrenaline (0.1 mg.kg-1 x h-1) or isoproterenol (12 micrograms.kg-1 x h-1) in female Sprague Dawley rats. To estimate the contribution of alpha and beta receptor stimulation to these effects, eight rats each were infused with prazosin (0.1 mg.kg-1 x h-1), metoprolol (1.0 mg.kg-1 x h-1), or the alpha and beta antagonist carvedilol (0.5 and 1.0 mg.kg-1 x h-1) alone and in combination with noradrenaline or isoproterenol. RESULTS: Noradrenaline and isoproterenol increased right ventricular systolic pressure (RVSP) from 30.3 (SEM 0.5) (n = 32) to 72.7(2.7) (n = 24) and 72.3(4.4) (n = 8) mm Hg, right ventricular (RV) dP/dtmax from 1848(70.3) to 4058(301) and 3612(366) mm Hg.s-1, and heart rate from 329(6) to 371(6) and 420(8) beats.min-1, respectively. Metoprolol completely prevented the isoproterenol induced haemodynamic changes, but neither metoprolol nor prazosin was able to significantly affect the pressure effect of noradrenaline (noradrenaline + metoprolol: 67.3(6.9) mm Hg, noradrenaline + prazosin: 67.0(3.8) mm Hg). The combination of both blockers, however, prevented the noradrenaline induced rise in RVSP (noradrenaline + metoprolol + prazosin: 36.5(5.1), and noradrenaline + prazosin + metoprolol: 30.0(1.2) mm Hg). Carvedilol (1.0 mg.kg-1 x h-1) significantly attenuated the noradrenaline induced RVSP increase (39.1(3.0) mm Hg), but not to the control range. Metoprolol or carvedilol completely prevented the noradrenaline elicited increases in heart rate (254(7) and 287(20) min-1) and RVdP/dtmax, but prazosin alone had no effect on the heart rate and RVdP/dtmax increase. Thus beta receptor blockade alone failed to significantly influence the noradrenaline induced increase of RVSP despite prevention of the increase in heart rate and RVdP/dtmax. Prazosin had a significant effect on RVSP only in combination with metoprolol. CONCLUSIONS: The combined effect of both alpha and beta blockade exceeds the pure addition of the single effects in the rat right ventricle. Moreover, we speculate that the failure to reduce the noradrenaline induced increase in RVSP by either alpha or beta blockade alone is due to the stimulation of the receptor that is not affected by the respective blocker.     

The influence of metyrapone on the synthesis and release of prostaglandins from the pregnant rat uterus in vitro

1 Metyrapone (150 mg/kg, s.c. or i.p.) an inhibitor of corticosteroid biosynthesis, significantly reduced the release of prostaglandins of the F-type from isolated preparations of pregnant rat uteri in vitro, on day 22 - the expected day of delivery. 2 Metyrapone and indomethacin administered in vitro both inhibited the conversion of 14C-arachidonic acid to prostaglandin E2 by homogenates of day 22 pregnant rat uteri. Metyrapone was approximately 150 times less potent than indomethacin. Although indomethacin also inhibited prostaglandin F2alpha production, metyrapone stimulated synthesis of this prostaglandin. The differential inhibition of prostaglandin synthesis by metyrapone may reflect sensitivity of the inhibitor to changes in experimental conditions. 3 Inhibition of prostaglandin synthesis may explain the effects of metyrapone on parturition in the rat.     

The in vivo relationship between blood flow, contractions, pH and metabolites in the rat uterus

Little is known about the relationship between smooth muscle contractile activity and its blood supply. We have therefore investigated this in the rat uterus, using laser-Doppler flow measurement and intra-uterine pressure recordings. We found an inverse linear relationship between flow and contractile activity. There was no evidence for a critical level of flow, above which function is maintained and below which it declines; even small reductions in blood flow decreased uterine force. Force was rapidly restored upon reperfusion. Reactive hyperaemia was absent from all but 6 of the 41 preparations studied. We used 31P nuclear magnetic resonance (NMR) spectroscopy to measure concentrations of adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi) and intracellular pH (pHi) simultaneously with force and flow. Reductions in flow were associated with significant reductions in [ATP], [PCr] and pHi, and an increase in [Pi]. These changes were related to flow significantly and linearly and their effects on force may be additive. These data show that uterine smooth muscle is closely dependent upon its blood supply for maintaining both normal force production and metabolite levels. Consequently, even small decrements in flow may have deleterious functional effects.     

The hypotensive effect of cisapride in rat

1. Cisapride is a prokinetic agent believed to facilitate acetylcholine release from the myenteric plexus of the gut. The aim of the present study was to investigate the effect of cisapride on blood pressure and the effects of muscarinic receptor antagonists on the cisapride-induced blood pressure changes. 2. Cisapride was given i.v. alone or 10 min after muscarinic receptor antagonists. Cisapride given i.v. produced a significant decrease in blood pressure in a dose-related manner. Atropine, AF-DX 116 and 4-DAMP given 10 min before cisapride injection, partially inhibited the hypotensive response to cisapride. In pithed rat, the effect of cisapride on blood pressure remained unaltered. 3. This study indicates that the action of cisapride is not through central mechanisms and part of cisapride's effect is through the cholinergic system.     

Metabolism of oxytocin in rat uterus and placenta in late gestation

Concentrations of oxytocin (OT) peptide increase in rat uterine tissues at the time of parturition. We have measured the rate of OT metabolism in these tissues in late gestation to determine whether a decrease in OT catabolism is responsible for the increase in OT concentrations. Uterine and placental tissues were obtained from groups of rats at Days 16, 19, 21, 21.5, 22, and after delivery of the first pup. Delivery usually occurs in the early afternoon of Day 22. Some animals were treated with the estrogen receptor blocker tamoxifen, which will delay parturition by approximately 24 h. Cytosolic and microsomal preparations obtained using ultracentrifugation were incubated with radiolabeled OT. Metabolites were separated using HPLC, and enzyme kinetic parameters were calculated. OT was actively metabolized in both uterine and placental tissues. Total oxytocinase activity was similar in the two tissues. In uterine tissues, activity was greater in the cytosolic fractions. In placenta, activity was evenly distributed between the cytosolic and microsomal fractions. The cytosolic fractions of each tissue contained predominantly post-proline endopeptidase activity, whereas the microsomes contained predominantly aminopeptidase activity. There was a slight trend to decreasing oxytocinase activity with advancing gestation in both subcellular fractions, but this was statistically significant only in the microsomal fraction. The maximal decline in activity was only 25-50%. Tamoxifen treatment had no effect on oxytocinase activity. We conclude that rat uterine and placental tissues contain post-proline endopeptidase and aminopeptidase activities that metabolize OT. It is doubtful that changes in these activities are major factors in regulating the increase in OT concentrations measured in rat intrauterine tissues at the time of parturition.     

Ontogeny of estrogen receptor messenger ribonucleic acid expression in the postnatal rat uterus

During the first 2 wk of postnatal life, the rodent uterus undergoes a period of marked growth and differentiation. To further examine the role of the estrogen receptor (ER) in the mediation of uterine development, we analyzed the ontogeny of ER mRNA expression in the postnatal rat uterus using in situ hybridization. ER mRNA was present in the uterine stroma on the day of birth and progressively increased in abundance during the first 2 wk of postnatal life. In contrast, ER mRNA was not detectable in the luminal epithelium at birth and did not become abundant in this region until postnatal day (P) 7. ER mRNA abundance increased in the luminal epithelium and in the invaginating and fully formed glandular epithelium during the second week of life. At P21 ER mRNA was more abundant in the glandular epithelium than in any other uterine cell type. These results are consistent with, and extend the findings of, previous studies using uterine homogenate binding assays and immunohistochemistry to define ER ontogeny in rodents. Delineation of the temporal and cell-type specific pattern of ER mRNA ontogeny in the postnatal rat uterus furthers our understanding of the molecular basis of both endogenous and exogenous estrogen effects on uterine growth and development.