Contractility Of Myometrial Strips Research Articles

β- and β-adrenergic receptors stimulation relaxes porcine myometrium in the peri-implantation period.

These studies were to demonstrate whether the β-receptor is involved in regulating the contractility of the swine myometrium in the peri-implantation period and to compare a relaxing activity of selective β- and β-adrenergic agonists (salbutamol and BRL 37344, respectively). Myometrial strips were collected form the gilts ( = 8) on d 12 to 14 of pregnancy. Changes in the contractility of myometrial strips were assessed further to the administration of increasing concentrations of the agonists (10 to 10 ) with and without β-adrenergic receptor antagonists: butoxamine, propranolol, and bupranolol at 10 . Moreover, the -log EC (pD) of the agonists were compared. Following the incubation of myometrial strips with salbutamol and BRL 37344, a significant ( < 0.05 to 0.001) reduction in the contractility, seen as decreased tension, amplitude, and frequency of contractions, as compared to the pretreatment period was noted, although salbutamol induced these changes at a concentration of 10 to 10 , whereas BRL 37344 induced them at 10 to 10 . Salbutamol exerted a significantly ( < 0.001) more potent reduction of the tension (pD = 6.98 ± 0.93 [SD]) than BRL 37344 (pD = 3.41 ± 0.1.61). The impact of salbutamol was neutralized by all administered antagonists, while a relaxing effect of BRL 37344 was completely inhibited by bupranolol and partially by propranolol. The data indicate that the β-adenergic receptor is involved in the regulation of smooth muscle contractility in the swine uterus in the peri-implantation period and its activation triggers relaxation of the myometrium to a lesser degree than the activation of the β-adrenergic receptor.

Effects of levobupivacaine and bupivacaine on rat myometrium

To study the effect of levobupivacaine and bupivacaine on the contractility of isolated uterine muscle strips from pregnant and non-pregnant female rats. Full-thick myometrial strips were prepared from 18- to 21-day pregnant (n=8) and non-pregnant rats (n=7). After contractions became regular, strips were exposed to cumulative concentrations of the two drugs from 10(-8) to 10(-4) mol/L, amplitude and frequency of the uterine contraction was recorded. Two local anesthetics caused a concentration dependent inhibition on contractility of myometrial strips from pregnant and non-pregnant rats. In the myometrium from non-pregnant rats, -logIC(50) of levobupivacaine and bupivacaine were 4.85 and 4.25 respectively. In the myometrium from pregnant rats, similar concentrations of levobupivacaine and bupivacaine were observed, -logIC(50) were 2.7 and 2.9 respectively. Levobupivacaine produced an increase in amplitude of contractions, while bupivacaine showed an increased trend in frequency. These results demonstrate that levobupivacaine and bupivacaine may inhibit myometrium contractility. The inhibitory effect of levobupivacaine or bupivacaine is not enhanced by gestation in rat. Levobupivacaine may have more positive influence than bupivacaine in pregnant myometrium.

A role for voltage‐gated, but not Ca2+‐activated, K+ channels in regulating spontaneous contractile activity in myometrium from virgin and pregnant rats

The roles of voltage-gated (K(V)) and large conductance Ca2+-activated K+ (BK(Ca)) channels in regulating basal contractility in myometrial smooth muscle are unresolved. The aim of this study was to determine the effects of inhibition of these channels on spontaneous rhythmic contraction in myometrial strips from four groups of rats: nonpregnant and during early (day 7), mid- (day 14), and late (day 21) pregnancy. BK(Ca) channels were inhibited using iberiotoxin (1-100 nM), paxilline (1-10 microM) or penitrem A (1-500, or 3000 nM); K(V) channels were inhibited using tetraethylammonium (TEA; 1-10 mM) and/or 4-aminopyridine (4-AP; 1-5 mM). Contractility was assessed as mean integral tension (MIT). Time/vehicle controls were also performed. None of the selective BK(Ca) channel inhibitors significantly affected contractility in myometrial strips from either nonpregnant or pregnant animals. 4-AP caused concentration-dependent increases in MIT in myometrium in all four groups. TEA (5 and 10 mM) significantly increased MIT in myometrium from nonpregnant, and mid- and late pregnant rats, but not in myometrium from early pregnant rats. TEA and 4-AP still caused an increase in MIT following treatment with 3000 nM penitrem A or a combination of propranolol, phentolamine, atropine (all 1 microM) and capsaicin (10 microM) in myometrial strips from nonpregnant rats. These results indicate that whereas BK(Ca) channels play little or no part in controlling basal rhythmicity in rat myometrium, K(V) channels appear to play a crucial role in this regard, especially during mid- and late pregnancy.

Shortening increases spontaneous contractility in myometrium from pregnant women at term

The purpose of this study was to determine whether shortening alters spontaneous contractility in myometrial strips that are obtained from pregnant women. Isometric contractions were measured in myometrial strips that were obtained at cesarean delivery from 14 pregnant women at term. After 2 hours of stretching, the strip lengths were decreased by 4%, 6%, or 8%. Spontaneous contractility was measured for 120 minutes with or without prostaglandin synthase inhibitor indomethacin (10 -5 mol/L), and the cumulative concentration response to oxytocin was determined. Contractility was increased by 29% and 34% in strips that shortened by 4% and 6%, respectively. Preincubation with indomethacin increased contractility by 15% in stretched strips and decreased contractility by 30% and 19% in 4% and 6% strips, respectively. Contraction frequency was increased by 26% and 53% for the strips that were shortened to 6% and 8%, respectively. These increases were prevented by indomethacin. The oxytocin responses were similar at all lengths. Shortening of myometrial strips from pregnant women at term increases spontaneous contractility by a mechanism that apparently involves prostaglandins.

ETA and ETB endothelin receptors in human myometrium characterized by the subtype selective ligands BQ123, BQ3020, FR139317 and PD151242.

ETA selective (BQ123, FR139317, PD151242) and ETB selective (BQ3020) ligands were used to define the binding characteristics and contractile function of endothelin receptor subtypes in human myometrium. In saturation binding assays with 10 microns-thick tissue sections [125I]endothelin-1 (ET-1) bound with a single affinity to receptors in the myometrium (Kd, 1.19 +/- 0.17 nM) and adjacent endometrium (Kd, 1.39 +/- 0.51 nM). Competition binding assays in myometrium revealed a heterogeneous population of receptors with BQ123 (Kd ETA, 1.43 +/- 0.33 nM; Kd ETB, 39.91 +/- 9.06 microM), FR139317 (Kd ETA, 2.54 +/- 0.87 nM; Kd ETB, 89.79 +/- 24.34 microM) and BQ3020 (Kd ETA, 4.57 +/- 0.58 microM; Kd ETB, 90.07 +/- 19.53 nM). The presence of these receptors in myometrium was confirmed by saturation assays with the new ETA selective ligand [125I]PD151242 (Kd, 0.93 +/- 0.08 nM; Bmax 138.7 +/- 1.0 fmol/mg protein) and the ETB selective [125I]BQ3020 (Kd, 0.62 +/- 0.07; Bmax 44.5 +/- 1.1 fmol/mg protein). Reverse-transcriptase PCR assays detected mRNA encoding both receptor subtypes in myometrium. Autoradiography with radiolabelled PD151242 and BQ3020 demonstrated that ETA receptors were the predominant subtype in the myometrium and identified a population of ETB receptors in the endometrium. In tissue bath experiments, an ET-1-induced increase in contractility of myometrial strips was antagonized by 10 microM FR139317 but not by BQ123 at the same concentration. The ETB agonist BQ3020, which is a potent agonist in animal tissue, did not increase contractility when tested at concentrations up to 2 microM.

Platelet-activating factor in human decidua: Its role in parturition

Platelet-activating factor (PAF) has been shown to play an important role in both fetal lung maturation and in parturition and it has been demonstrated that part of the PAF present in the amniotic fluid is associated with surfactant and, therefore, of lung origin. PAF receptors are present in type II pneumonocytes and the addition of the autacoid promotes both glycogenolysis and increased surfactant secretion from these cells. Moreover, type II pneumonocytes and a human amnion-derived cell line (WISH) have the capability of metabolizing PAF to ethanolamine phospholipids. It has also been established that PAF will cause intracellular Ca2+ mobilization and promote myosin phosphorylation and increased contractility in myometrial strips. Increased PAF biosynthesis in fetal tissues takes place during the latter stages of pregnancy, simultaneously with a decrease in the activity of PAF-acetylhydrolase (PAF-AH) in maternal plasma. The activity of PAF-AH is decreased by the administration of estrogens in vivo and is increased by glucocorticoids and progestins. A number of agents lower the secretion of PAF-AH by decidual macrophages, including 1,25-(OH)2D3, bacterial lipopolysaccharides, and some cytokines (IL1, TNF-α). This inhibitory action may result in higher levels of PAF and increased myometrial contractility as a consequence of infectious processes. PAF causes a profound intestinal necrosis when administered to rats by intravenous injection. Pretreatment with dexamethasone protects against this disease. The presence of PAF-AH in human milk may explain the protective effect of mother's milk against necrotizing enterocolitis.

The effects of lipoxygenase metabolites of arachidonic acid on human myometrial contractility

The effects of the lipoxygenase products of arachidonic acid, 5- and 12-hydroxyeicosatetraenoic acid (5- and 12-HETE) and leukotriene B 4 (LTB 4), on the spontaneous contractility of lower uterine segment human myometrial strips obtained prior to labour have been studied in vitro . 5-HETE gave a dose- dependent (10–500ng) increase in both the rate of contractions and overall contractility of myometrial strips while 12-HETE and LTB 4 had no effect at the same concentrations. Prostaglandin F 2 ▪ (50ng) contracted all myometrial strips in a similar pattern to 5-HETE but was approximately 10 times more potent. The effect of 5-HETE may be direct or perhaps indirect via interaction with the cyclo-oxygenase pathway. The findings do not disprove the contention that the onset of parturition may be characterized by a switch in arachidonic acid metabolism in intra-uterine tissues from lipoxygenase to cyclo-oxygenase products.