Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During a 1-yr period, we evaluated prospectively the use of nitroglycerin (NTG) to relieve severe intrapartum fetal distress related to uterine hyperactivity. Sixty to ninety micrograms of NTG were injected intravenously (i.v.) within 2-5 min after onset of severe fetal distress after oxygen administration, left lateral decubitus, and discontinuation of any ongoing oxytocin infusion (62%) had failed to resolve the fetal heart rate abnormality. A second dose (60 or 90 micrograms) was used 2-3 min later as required. NTG was completely effective in 22 cases (fetal distress resolution within 4-5 min with restoration of normal uterine activity) and partially but sufficiently effective in the remaining 2 cases (fetal distress resolution within 4-5 min with residual mild uterine hyperactivity). However, a second dose was required for nine parturients (38%). Six parturients (25%) developed hypotension 2 min after the first NTG injection, with a mean nadir of 93.2 mm Hg (minimum 85 mm Hg). Hypotension was always rapidly reversed with a small single dose of ephedrine (4.5-6 mg). In conclusion, we found small doses (60-180 micrograms) of IV NTG to be associated with resolution of severe fetal distress related to uterine hyperactivity along with negligible side effects.
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PMID:Intravenous nitroglycerin to relieve intrapartum fetal distress related to uterine hyperactivity: a prospective observational study. 914 42

In the present paper, we examined a mechanism of the papaverine induced relaxation in the smooth muscle of non-pregnant rat uterus. The hyperosmotic 65 mM KCl (H-65K+)-or oxytocin-induced contraction in the uterus was inhibited by an addition of papaverine in a concentration-dependent manner. Papaverine did not increase both cAMP and cGMP contents in the uterus in the presence of H-65K+ or oxytocin. In fura 2 loaded muscles, papaverine did not affect an increase of [Ca2+]i level by high K+ or oxytocin. In permeabilized muscles, papaverine had no effect on the Ca2+-induced contraction. H-65K+ and oxytocin increased the rate of oxygen consumption 1.8 and 1.5 times higher than that in the resting condition, respectively. The increase of oxygen consumption in the H-65K+ or oxytocin was significantly inhibited by papaverine (1-100 microM). These results suggested that papaverine inhibits smooth muscle contraction mainly by inhibition of mitochondrial respiration in rat uterus as well as guinea pig ileum, which shows a highly spontaneous activity and a highly metabolic dependency of a contraction.
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PMID:Mechanism of relaxant response to papaverine on the smooth muscle of non-pregnant rat uterus. 1108 80

Accumulating evidence indicates that gonadal steroids modulate functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which has been closely linked to the pathophysiology of anxiety and depression. However, the effect of the natural menstrual cycle on HPA axis responsivity to stress has not been clearly described. In nine healthy women, metabolic and hormonal responses to treadmill exercise stress during the early follicular phase of the menstrual cycle, when gonadal steroid levels are low, were compared with responses in the midluteal phase of the cycle, when both progesterone and estrogen levels are relatively high. Exercise intensity was gradually increased over 20 min to reach 90% of each subject's maximal oxygen consumption during the final 5 min of exercise. Basal plasma lactate, glucose, ACTH, vasopressin, oxytocin, and cortisol levels were similar in the two cycle phases. However, in response to exercise stress, women in the midluteal phase had enhanced ACTH (P < 0.0001), vasopressin (P < 0.01), and glucose (P < 0.001) secretion. These findings suggest that relatively low levels of gonadal steroids during the early follicular phase of the menstrual cycle provide protection from the impact of stress on the HPA axis.
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PMID:Increased vasopressin and adrenocorticotropin responses to stress in the midluteal phase of the menstrual cycle. 1139 50

Oxygen free radicals have been suggested to play important roles in atherogenesis and other pathological processes in the blood vessel wall. The vascular wall contains large amounts of extracellular superoxide dismutase (EC-SOD), which is produced and secreted to the extracellular space by smooth muscle cells. In this study, we investigated the influence of factors regulating tension and proliferation of vascular smooth muscle cells and of some interstitial matrix components on EC-SOD expression. The expression and secretion of EC-SOD were upregulated by histamine, vasopressin, oxytocin, endothelin-1, angiotensin II, serotonin, heparin, and heparan sulfate and were downregulated by platelet-derived growth factors-AA and -BB, acidic and basic fibroblast growth factors, and epidermal growth factor. The responses were slow and developed over several days. The findings suggest that various physiological and pathological conditions might markedly influence EC-SOD expression, significantly altering the susceptibility of the vascular wall to effects of the superoxide radical.
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PMID:Vasoactive factors and growth factors alter vascular smooth muscle cell EC-SOD expression. 1155 52

Erythromycin has a well-known dual effect on the contractility of the gastrointestinal system and recently has also been shown to inhibit contractions of the rat myometrium. The aim of the present study was to investigate the effects of clarithromycin on oxytocin, prostaglandin F2alpha (PGF2alpha) and KCl-induced contractions of human myometrium in vitro. Myometrial strips were obtained from pregnant women undergoing elective Cesarean section and the strips were suspended in a jacketed organ bath filled with Krebs solution at 37 degrees C (pH 7.4) and continuously aired with 95% oxygen and 5% carbon dioxide. Isometric contractions were measured using a force displacement transducer. Oxytocin, PGF2alpha, KCl and clarithromycin were applied to the tissue bath and the amplitude and frequency of contractions were evaluated at 20-min intervals. Freidmann analysis of variance, Kruskal Wallis and Wilcoxon Rank tests were used for statistical analysis of the data. Clarithromycin dose dependently inhibited the amplitude of contractions independent of the stimulus. Pre-treatment with apamin prevented clarithromycin-induced effects on amplitude and frequency of contractions. We conclude that the macrolide antibiotic clarithromycin may have a direct inhibitory effect on contractions of human myometrium.
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PMID:Clarithromycin inhibits myometrial contractions in isolated human myometrium independent of stimulus. 1223 15

The objective of this study was to establish an experimental model for extracorporeal perfusion of swine uterus. In order to validate this model, we examined some biochemical parameters and determined the effect of oxytocic drugs (Oxytoxin, Prostaglandin E (2)) on extracorporeal perfused swine uteri. Thirty swine uteri were perfused with Krebs-Ringer bicarbonate-glucose buffer for a period up to eleven hours with the aim to preserve a viable organ, which should be responsive to hormones. The intrauterine pressure was recorded after administration of various concentrations of oxytocin and prostaglandin E (2). Perfusate pH, perfusate lactate, partial oxygen and carbon dioxide tensions, oxygen saturation, and hydrogencarbonate levels in the perfusate, all indicators of tissue ischemia or cell necrosis, showed good preservation of the organ for up to seven hours. We examined the relation of intrauterine pressure to oxytocin and prostaglandin E (2). Both were able to induce contractions of the uterus, whereas prostaglandin E (2) produced rhythmical contractions of smaller amplitude and a higher frequency. We could demonstrate that our perfusion system was able to preserve the swine uterus in a functional condition appropriate for the study of physiological questions.
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PMID:The extracorporeal perfusion of swine uterus as an experimental model: the effect of oxytocic drugs. 1451 66

The paper presents a new theory on the physiological mechanism of initiation of luteolysis, function of endometrial cells and protection of corpus luteum. This theory is based on previous studies published by the authors and their coworkers on the retrograde transfer of PGF2alpha in the uterine broad ligament vasculature during the estrous cycle, early pregnancy and pseudopregnancy. The studies were focused on cyclic changes in uterine blood supply and the apoptosis of endometrial cells. Moreover, the results of many other authors are cited. The statements of the theory are as follows: 1. The initiation of luteolysis is a consequence of regressive changes in the endometrium which are due to the reduction of the uterine blood supply below the level necessary to provide for the extended needs of active endometrium. 2. During the luteal phase, both a considerable increase in uterine weight and a decrease in blood flow through the uterine artery, resulting from increasing progesterone concentration, reduce the uterine blood supply. In comparison to the volume of blood flowing to the porcine uterus during the estrus period, only 30-40% of the blood volume is determined on day 12 of the estrous cycle. The uterine weight at that time is 40-60% larger than that in the early luteal phase. Thus, due to the considerable constriction of uterine blood vessels, there is a discrepancy between the requirement for oxygen and other factors transported by blood and the possibility of supplying the uterus with these substances. After reaching the threshold of uterine blood supply level, which in pigs takes place around day 12 of the estrous cycle, regressive changes and PGF2alpha release from endometrial cells occurs. 3. Estrogens and progesterone are the major factors affecting blood flow in vessels supplying the uterus. The factors that modulate, complement and support vasodilation and vasoconstriction are: PGE2, LH, oxytocin, cytokines, neurotransmitters and other local blood flow regulators. In some animal species these modulators, especially those of embryonic origin, may be crucial for the status of uterine vasculature. 4. During early pregnancy, the action of embryo signals (estrogens, cytokines), endometrial PGE2 as well as LH results in the relaxation of the uterine artery (pigs: day 12) and, consequently, in an increase in uterine blood supply. This reaction of the maternal recognition of pregnancy effectively prevents regressive changes in well developed endometrial cells to occur. 5. Local uptake and retrograde transfer of PGF2alpha into the uterine lumen during early pregnancy protects corpus luteum from PGF2alpha luteolytic action. 6. During the period of regressive changes resulting from the limited uterine blood supply, endometrial cells restrain PGF2alpha synthesis. They are, however, still capable of releasing prostaglandin when uterine blood supply is improved after the embryo appears in the uterus. This potential capability for PGF2alpha synthesis was demonstrated in in vitro studies when endometrial cells collected during its regressive phase were incubated in medium and stimulated by LH and oxytocin. 7. Prostaglandin F2alpha pulses in venous blood flowing from the uterus do not confirm pulsatile secretion of PGF2alpha. The pulses may result from the pulsatile excretion of PGF2alpha with venous blood according to the rhythmic uterine contractions associated with oxytocin secretion. 8. The results supporting this concept are presented and discussed in due course. The critique of Bazer and Thatcher's theory on exocrine versus endocrine secretion of prostaglandin F2alpha during the estrous cycle is also depicted.
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PMID:Uterine blood supply as a main factor involved in the regulation of the estrous cycle--a new theory. 1466 52

The corpus luteum (CL) is a transient reproductive gland that produces progesterone (P), required for the establishment and maintenance of pregnancy. Although the regulation of bovine luteal function has been studied for several decades, many of the regulatory mechanisms involved are incompletely understood. We are far from understanding how these complex mechanisms function in unison. The purpose of this overview is to stress important steps of regulation during the lifetime of CL. In the first part, the importance and regulation of angiogenesis and blood flow during CL formation is described. The results underline the importance of growth factors especially of vascular endothelial growth factor A (VEGF A) and basic fibroblast growth factor (FGF-2) for development and completion of a dense network of capillaries. In the second part, the regulation of function by endocrine/paracrine- and autocrine-acting regulators is discussed. There is now more evidence that besides the main endocrine hormones LH and GH local regulators as growth factors, peptides, steroids and prostaglandins are important modulators of luteal function. During early CL development until mid-luteal stage oxytocin, prostaglandins and P itself stimulate luteal cell proliferation and function supported by the luteotropic action of a number of growth factors. The still high mRNA expression, protein concentration and localization of growth factors [VEGF, FGF-1, FGF-2, insulin-like growth factors (IGFs)] in the cytoplasm of luteal cells during mid-luteal stage suggest maintenance (survival) functions for growth factors. In the absence of pregnancy regression (luteolysis) of CL occurs. Progesterone itself regulates the length of the oestrous cycle by influencing the timing of the luteolytic signal prostaglandin F2alpha (PGF2alpha) from the endometrium. The cascade of mediators afterwards is very complex and still not well-elucidated. Evidence is given for participation of blood flow, inflammatory cytokines, vasoactive peptides (angiotensin II and endothelin-1), reactive oxygen species, angiogenic growth factors (VEGFs, FGFs, IGFs) and decrease of the classical luteotropic components as LH-R, GH-R, P450(scc) and 3beta-HSD. Despite of differences in methodology and interpretations, progress has been made and will continue to be made.
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PMID:Regulation of corpus luteum function in cattle--an overview. 1522 77

Gentamicin sulfate, an aminoglycoside antibiotic known to cause depression of neuromuscular function, is a drug of choice in intrauterine antibiotic treatment of bovine chronical or subclinical uterine infections but its effects on the contractility of the cow uterus have not been studied. The aim of this study was to characterize, in vitro, the effect of gentamicin sulfate on spontaneous as well as prostaglandin F2alpha (PGF2alpha) and oxytocin-induced contractility of the non-pregnant cow uterus. Myometrial strips were isolated from non-pregnant cows in follicular phase and suspended in a jacketed organ bath filled with Krebs solution at 37 degrees C (pH 7.4) continuously bubbled with 95% oxygen and 5% carbon dioxide and isometric contractions were recorded using isometric force displacement transducer. After manifestation of the spontaneous contractions during equilibration period the test substances PGF2alpha (1 microM), oxytocin (2.5 mIU/ml bath fluid) and gentamicin sulfate (150-600 microm) were added to the bath. The effects of gentamicin sulfate on amplitude (g) and frequency of spontaneous and the agonist-induced contractions were evaluated by 20 min intervals. Data were statistically analyzed using the Student's t-test and Wilcoxon signed-rank test where appropriate. P <0.05 was considered to be significant. Gentamicin sulfate inhibited spontaneous, as well as oxytocin or PGF2alpha-induced contractions in a dose-dependent manner. Although both the frequency and amplitude of contractions were significantly inhibited by gentamicin sulfate, the effect on the frequency of the spontaneous and agonist-induced contractions were more prominent than on the amplitude. The result from this in vitro study indicated that gentamicin sulfate inhibits spontaneous as well as oxytocin and PGF2alpha-induced contractions of myometrium isolated from non-pregnant cows. This may be of importance considering the potentially negative effect of gentamicin sulfate on uterine involution in cows with puerperal endometritis, resulting in impairment of fertility performance.
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PMID:Effects of gentamicin sulfate on the contractility of myometrium isolated from non-pregnant cows. 1530 70

In this paper, we review our current understanding of the medicinal chemistry of the major peptide systems, which influence body fluid homeostasis. Electrolytes play pivotal roles in intra- and intercellular communication, acid-base equilibrium and, when bound to several macromolecules, they regulate a myriad of enzymatic proteins, receptors and transcription factors. Cell turgor influences the plasma membrane, which activates mechanically-gated ion channels or mechanoreceptors, and the expression of a number of genes which underlie long-term metabolic responses to hormones, substrates and reactive oxygen intermediates. The altered kinetics and enzymatic cleavage of peptides during water-electrolyte imbalance can contribute to cardiac and renal damage associated with elevated blood pressure. Identification of the enzymes which are responsible for cleavage, together with emerging information about the mechanisms of action and structures of regulatory and effector peptides, has laid a foundation for the discovery of novel drugs, some of which are in use or are now undergoing evaluation in experimental trials. The development of models of hydrosaline challenge with relative efficiency to induce selective water-electrolyte imbalance has permitted the identification of kallikrein-kinin, renin-angiotensin-aldosterone, vasopressin-oxytocin, thyrotropin-releasing hormone and luteinizing hormone-releasing hormone as susceptible substrates. At present, the angiotensin-I converting enzyme inhibitors are well-known efficacious, orally active, blood pressure-lowering agents which have been used in hypertensive patients. In addition to several new analogues of this class of drug, some selective dual inhibitors of angiotensin-I converting enzyme and neutral endopeptidase and inhibitors of aminopeptidases are now also being rationally assayed and their beneficial effects on hypertension and hydromineral balance indicate that this type of drug may have powerful therapeutic effects for disorders of body fluid homeostasis.
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PMID:Peptide metabolism and the control of body fluid homeostasis. 1532 Jul 88


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