scholarly journals Progesterone decreases the relaxing effect of the β3-adrenergic receptor agonist BRL 37344 in the pregnant rat myometrium

Reproduction ◽  
2009 ◽  
Vol 138 (2) ◽  
pp. 383-390 ◽  
Author(s):  
Renáta Minorics ◽  
Róbert Gáspár ◽  
Adrienn Gál ◽  
Anna Klukovits ◽  
George Falkay
Keyword(s):  
Functional Activity ◽  
Contractile Activity ◽  
Relaxation Effect ◽  
Inhibitory Effect ◽  
Uterine Contractility ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
The Right ◽  
Brl 37344 ◽  
Relaxing Effect

Although the published results regarding the function of the β3-adrenergic receptors (β3-ARs) in the regulation of smooth muscle activity are very promising, the question of the mechanism of β3-ARs' action in the pregnant myometrium cannot be fully answered by human investigations. To assess whether it possesses an essential role in the regulation of uterine contractility in pregnant rats, as in humans, we performed functional, western blotting and molecular biology experiments on the late-pregnant rat myometrium. The influence of progesterone on the function of the β3-ARs was also investigated. We demonstrated the presence and the functional activity of the β3-ARs in the late-pregnant rat myometrium. The maximum dose-dependent uterus-relaxing effect of the selective β3-agonist BRL 37344 was recorded at the end of pregnancy in rats, similarly as in humans. The extent of its relaxing action was regarded as moderate. The expression of β3-AR protein and mRNA remained unchanged during the investigated period. The administration of progesterone had no effect on the β3-AR mRNA and protein expression or the maximum relaxation effect of BRL 37344, but shifted the dose–response curve to the right and decreased the synthesis of the second messenger, cAMP. It can be concluded that the β3-ARs play an additional role in the regulation of the contractile activity of the pregnant rat uterus. The inhibitory effect of progesterone on the functional activity of the β3-ARs may have important consequences in the case of human application if this effect is also demonstrated in pregnant human myometrial tissue.

PLASMA PROLACTIN AND PROGESTERONE RESPONSES TO MATING ARE ALTERED IN AGED RATS

1981 ◽  
Vol 90 (2) ◽  
pp. 179-191 ◽  
Author(s):  
S. HENDRICKS ◽  
C. A. BLAKE
Keyword(s):  
Plasma Concentrations ◽  
External Jugular Vein ◽  
Female Rats ◽  
Plasma Prolactin ◽  
Aged Rats ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Plasma Progesterone ◽  
The One ◽  
The Right

The effects of varying amounts of copulatory stimulation on patterns of plasma concentrations of prolactin and progesterone were evaluated in 3- and 12-month-old female rats. The 12-month-old group included rats which still exhibited oestrous cycles and rats in persistent vaginal oestrus (PVO). The extent of copulatory stimulation was defined by the number of intromissions received during mating: ≤5,15 or > 50. Blood samples were drawn over the 8 days after mating through a cannula inserted into the right external jugular vein. Plasma from the samples was assayed for prolactin and progesterone. In aged but still cyclic rats, pregnancy rates were positively correlated with the number of intromissions received during mating. Only one rat in PVO became pregnant. All animals which became pregnant and rats in PVO which, after mating, exhibited a disruption of the pattern of PVO, showed the nocturnal surge of plasma prolactin characteristic of pregnant and pseudopregnant rats. While these surges persisted until day 8 after mating in pregnant animals, they were absent by this time in the rats in PVO. Prolactin surges were present in some but not all of the aged rats which did not become pregnant. Progesterone concentrations were raised in all pregnant animals except the one pregnant rat in PVO and, while not related to the number of intromissions, concentrations were higher 8 days after mating in young compared with those in aged pregnant rats. Plasma progesterone was low in rats in PVO regardless of disruption of the pattern of PVO. We have concluded that the failure of limited copulatory stimulation to induce pregnancy in older rats results, at least in part, from its failure to initiate nocturnal prolactin surges. Nevertheless, our data suggest that matings which are not experimentally limited should provide ample stimulation to establish such surges. Although reduced plasma concentrations of prolactin and progesterone at pro-oestrus and reduced plasma progesterone through part of gestation may contribute to decreasing fertility in aged rats, other unidentified factors appear to be involved in mediating the capacity of extensive copulatory stimulation to induce pregnancy in these animals.

scholarly journals Up-regulation of rat myometrial phospholipases Cβ1 and Cβ3 correlates with increased term sensitivity to carbachol and oxytocin

2005 ◽  
Vol 187 (2) ◽  
pp. 197-204 ◽  
Author(s):  
E Houdeau ◽  
A Lévy ◽  
S Mhaouty-Kodja
Keyword(s):  
Uterine Contraction ◽  
Longitudinal Muscle ◽  
Inositol Phosphate ◽  
Contractile Activity ◽  
Positive Control ◽  
Maximal Response ◽  
Muscarinic Agonist ◽  
Uterine Contractility ◽  
Pregnant Rats ◽  
Oxytocin Receptors

In the present study, we compared rat uterine contractility and myometrial inositol phosphate (InsP) production in response to activation of muscarinic and oxytocin receptors during pregnancy and at term. The level of myometrial phospholipase (PL) Cβ was also determined by Western blotting at different stages of pregnancy and following administration of oestradiol, progesterone or vehicle. The results showed an increased potency of carbachol (CCh), a cholinergic muscarinic agonist, and oxytocin (OT) to enhance myometrial InsP production at term. This correlated with an increased potency of both agonists to induce contraction of the circular but not the longitudinal muscle. For both InsP production and contractile activity, the maximal response of CCh was unaltered, while that of OT was significantly increased. Interestingly, the increased responsiveness to CCh and OT was associated with an up-regulation of PLCβ1 and PLCβ3 enzymes. Such regulation is under the control of oestradiol since administration of this steroid to pregnant rats increased the amount of both enzymes by 200–260%. In contrast, progesterone administration was without effect. The present study presents the first evidence that the expression of rat myometrial PLCβ1 and PLCβ3 is under the positive control of oestradiol. This could participate in the enhancement of myometrial InsP accumulation and uterine contraction at term in response to CCh and OT. Based on contraction studies, we also propose that the longitudinal and circular uterine muscles differ in the regulation of the PLC pathway during pregnancy.

Fluprostenol-induced softening of the cervix of the pregnant rat

1983 ◽  
Vol 97 (2) ◽  
pp. 283-290 ◽  
Author(s):  
L. M. Williams ◽  
M. Hollingsworth ◽  
M. Dukes ◽  
I. D. Morris
Keyword(s):  
Binding Capacity ◽  
Direct Action ◽  
Prostaglandin E ◽  
Uterine Contractility ◽  
Serum Progesterone ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Uterine Contractions ◽  
Prostaglandin F

Fluprostenol, an analogue of prostaglandin F2α, administered s.c. to rats on day 18 of pregnancy increased cervical creep, or softness, by the following day. Doses of fluprostenol 100-fold larger were necessary to increase uterine contractions. Fluprostenol produced falls in serum progesterone concentrations, increases in 20α-dihydroprogesterone concentrations, no changes in oestradiol or relaxin concentrations and a reduction in the ovarian human chorionic gonadotrophin binding capacity in vitro. Fluprostenol was less potent in inducing cervical softness when administered per vaginam, and a dose which produced softening in pregnant rats was ineffective in ovariectomized steroid-maintained pregnant or pro-oestrous rats. The findings suggest that cervical softening by fluprostenol does not result from a simple direct action on the cervix or by increasing uterine contractions, but rather by an indirect hormonal action mediated by the ovaries. The results with the lowest dose of fluprostenol indicate that cervical softening could be produced without a sustained fall in serum progesterone concentrations. Fluprostenol is much more potent at increasing cervical softness in the pregnant rat than prostaglandin F2α or prostaglandin E2. With fluprostenol the ratio of dose to induce uterine contractility relative to that to produce cervical softness was greater than with these natural prostaglandins, indicating the greater selectivity of fluprostenol in the pregnant rat.

Immunohistochemical Localization of Cyclooxygenase-2 in Pregnant Rat Uterus by Sp-6 Acupuncture

2003 ◽  
Vol 31 (03) ◽  
pp. 481-488 ◽  
Author(s):  
Jeong-Sang Kim ◽  
Chang Su Na ◽  
Woo Jun Hwang ◽  
Byung Chul Lee ◽  
Ki Hyoung Shin ◽  
...  
Keyword(s):  
Acupuncture Treatment ◽  
Immunohistochemical Localization ◽  
Cyclooxygenase 2 ◽  
Uterine Contractility ◽  
Rat Uterus ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Complementary Method ◽  
Key Factor ◽  
Cox 2

As pregnancy advances, prostaglandins (PG) increase in the uterus, leading to elevated uterine contractility. Therefore, regulating the concentration of PG in the uterus can be a key factor for controlling the duration of labor. Since the synthesis of PGs in the uterus is catalyzed by cyclooxygenase-2 (COX-2), devising a tool to regulate the expression of COX-2 could provide a method for treating complicated labor. In this study, Sp-6 acupuncture treatment was evaluated for its potential in controlling uterine motility. Immunohistochemical methods showed the COX-2 enzyme was primarily found in the endometrium and myometrium of rat uterus. COX-2 expression in these two locations were intensified by pregnancy, but reduced by acupuncture at the Sp-6 acupoint. Uterine motility monitored during Sp-6 acupuncture was reduced by 28.15% (p < 0.05) and 19.88% (p < 0.05) in pregnant rats and non-pregnant rats, respectively. The significant reduction of uterine motility in pregnant rat suggests a role for Sp-6 acupuncture in regulating the expression of COX-2 during pregnancy. These results suggest that Sp-6 acupuncture could be used as a complementary method for controlling labor in human pregnancy.

LUTEOLYTIC EFFECTS OF PROSTAGLANDINS IN RAT PREGNANCY, AND REVERSAL BY LUTEINIZING HORMONE

1974 ◽  
Vol 76 (3) ◽  
pp. 583-596 ◽  
Author(s):  
Anna-Riitta Fuchs ◽  
E. Mok ◽  
K. Sundaram
Keyword(s):  
Saline Solution ◽  
Threshold Level ◽  
Inhibitory Effect ◽  
Concomitant Treatment ◽  
Indwelling Catheter ◽  
Pregnant Rats ◽  
Plasma Progesterone ◽  
Initial Values ◽  
The Right ◽  
Dose Dependent

ABSTRACT The influence of prostaglandin infusions on plasma progesterone (P) was determined in pregnant rats at various stages of gestation. Serial blood samples were collected from the right atrium through an indwelling catheter before, during and after prostaglandin (PG) administration. PGE2 and PGF 2α was given as intravenous infusions of 6 hours duration through the same catheter at rates varying from 0.33 to 5.5 μg/min (total dose: 125 to 2000 μg/rat). Control rats received an equal amount of 0.9 % saline solution. Prostaglandins suppressed plasma P levels at all stages of gestation, PGF2α being much more effective than PGE2. The effect of PGF2α was not dose-dependent above a threshold level of about 125 μg/rat. The decrease in plasma P was evident within 3 hours of the start of the infusion, with further decrease in the subsequent 3 hours of infusion. The degree of luteal suppression by PGF2α varied in the course of gestation, being greatest on days 10 and 18 of pregnancy and smallest on days 4 and 16. On days 10 and 18, plasma was reduced by 75 %, on the average, during the infusion of PGF2α with further decrease to 15 % of initial values within 24 hours. Pregnancy was terminated in these rats, but was maintained in most rats treated with PGF2α at other stages of gestation. Plasma P decreased, on the average, by 60 % during the infusion of PGF2α in all rats that remained pregnant, and progesterone concentrations remained at a level of 30 % of initial values for at least 2 days. Plasma P levels as low as 20 % of initial values were compatible with undisturbed gestation. Concomitant treatment with LH prevented the decrease in plasma P induced by PGF2α on days 4, 7 and 10, but had little effect on day 18. Prolactin, given alone or with oestradiol, was completely ineffective on day 10 but on day 4, prolactin had a marginal inhibitory effect on the PGF2α-induced fall in plasma progesterone.

Role of Extracellular Calcium and Calcium Sensitization in the Anti-Contractile Effect of Perivascular Adipose Tissue in Pregnant Rat Aorta

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 359-367 ◽  
Author(s):  
Aishah Al-Jarallah ◽  
Elsie Oommen ◽  
Lilly Chacko Verghese ◽  
Mabayoje A. Oriowo
Keyword(s):  
Adipose Tissue ◽  
Inhibitory Effect ◽  
Extracellular Calcium ◽  
Pregnant Rats ◽  
Perivascular Adipose Tissue ◽  
Pregnant Rat ◽  
Calcium Sensitization ◽  
Contractile Effect ◽  
Significant Difference ◽  
Gf 109203X

Previous studies have shown that the anti-contractile effect of the perivascular adipose tissue (PVAT) is attenuated in pregnancy. In the present investigation, we have examined the possibility that this loss of anti-contractile effect could be due to changes in calcium mobilization. PVAT exerted anti-contractile effect against 5-hydroxytryptamine (5-HT)-induced contractions of aorta segments from pregnant and non-pregnant rats and this anti-contractile effect was attenuated in segments from pregnant rats. Nifedipine (10–6 mol/L), an inhibitor of L-type dihydropyridine calcium channels, significantly reduced 5-HT-induced contraction of aorta segments from non-pregnant and pregnant rats with and without PVAT. The inhibitory effect of nifedipine against 5-HT-induced contractions was attenuated in PVAT-free aorta segments from pregnant rats. However, while PVAT reduced the effectiveness of nifedipine in aorta segments from non-pregnant rats, it partially restored the inhibitory effect of nifedipine in aorta segments from pregnant rats. Inhibitors of calcium sensitization, Y-27632 (10–6 mol/L) and GF 109203X (10–6 mol/L), significantly reduced 5-HT-induced contractions of PVAT-free aorta segments from non-pregnant and pregnant rats. Both inhibitors, however, were less effective in aorta segments from pregnant rats. The presence of PVAT reduced the effectiveness of Y-27632 and GF 109203X in aorta segments from pregnant and non-pregnant rats. Protein expression of Rho-associated protein kinase (ROCK) I and II was detected in aorta segments and PVAT from pregnant and non-pregnant rats. There was a reduction in the expression of both isoforms in aorta segments but not PVAT from pregnant rats. In addition, there was no significant difference in the expression of ROCK-I and ROCK-II in PVAT from pregnant and non-pregnant rats. We concluded that the loss of anti-contractile effect of PVAT in aorta segments from pregnant rats could be due to increased influx of extracellular calcium through nifedipine-sensitive dihydropyridine channels.

scholarly journals Dryopteris filix-mas (Dryopteridaceae) leaves inhibit mouse uterine activity

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Enitome E. Bafor ◽  
Wellington O. Omokaro ◽  
Osamuyi H. Uwumarongie ◽  
Uloma B. Elvis-Offiah ◽  
Osemelomen Omoruyi ◽  
...  
Keyword(s):  
Plant Extract ◽  
Inhibitory Effect ◽  
Mass Spectrometric ◽  
Uterine Contractility ◽  
River Bank ◽  
Uterine Activity ◽  
Uterine Contractions ◽  
Free Media ◽  
Relaxing Effect

Background: The plant Dryopteris filix-mas has been used traditionally for its uterine-stimulant effects.Aim: The current study is therefore aimed at investigating and determining the effect of the leaves of D. filix-mas on uterine contractility in vitro.Setting: Fresh leaves of D. filix-mas were collected from a river bank in the south-western part of Nigeria.Methods: The leaves of D. filix-mas were cleaned, dried and extracted in methanol. The extract (0.07 µg/mL–21.0 µg/mL) was tested on the isolated mouse uteri in order to determine activity on spontaneous-induced uterine contractions. Subsequently the extract (0.005 mg/mL and 0.05 mg/mL) was tested on oxytocin-induced contraction (0.00017 ng/mL–4.98 ng/mL) in calcium-containing media, submaximal oxytocin-induced contraction (0.116 ng/mL) in calcium-free media and in the presence of high KCl-induced uterine contractions (80 mM). The extract was also subjected to mass spectrometric determination of secondary metabolites.Results: The plant extract inhibited spontaneous-induced contractions with IC50 amplitude = 658.41 ng/mL ± 0.11 ng/mL and IC50 frequency = 175.32 ng/mL ± 0.53 ng/mL. The plant extract inhibited oxytocin-induced and high KCl-induced uterine contractions (p < 0.01 at 0.5 mg/mL). The plant extract had no effect on oxytocin-induced contractions under calcium-free conditions. Secondary metabolites belonging to classes of fatty acids, alkaloids, saponin glycosides, amino acids, limonoids, terpenes and porphyrins were identified.Conclusion: The current study reports an inhibitory effect of the plant on uterine contractility in this study, suggesting possible application as a tocolytic or as a contraceptive, as most contraceptive plants have shown uterine-relaxing effect.

Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies

2021 ◽  
pp. 1-8
Author(s):  
Beata Modzelewska ◽  
Marcin Jóźwik ◽  
Tomasz Kleszczewski ◽  
Stanisław Sulkowski ◽  
Maciej Jóźwik
Keyword(s):  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Reference Group ◽  
Ex Vivo ◽  
Contractile Activity ◽  
Organ Bath ◽  
Human Uterus ◽  
Uterine Contractility ◽  
Beta Adrenoceptor ◽  
Gynecological Malignancies

Objective: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. Design: This was a controlled and prospective ex vivo study. Setting: The work was conducted as a collaboration between 4 academic departments. Materials and Methods: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. Results: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). Limitations: These results require now to be placed into a firm clinical context. Conclusions: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.

scholarly journals Contractile and Endothelium-Dependent Dilatory Responses of Cerebral Arteries at Various Extracellular Magnesium Concentrations

1991 ◽  
Vol 11 (1) ◽  
pp. 161-164 ◽  
Author(s):  
Mária Faragó ◽  
Csaba Szabó ◽  
Eörs Dóra ◽  
Ildikó Horváth ◽  
Arisztid G. B. Kovách
Keyword(s):  
Smooth Muscle ◽  
Vascular Reactivity ◽  
Calcium Influx ◽  
Cerebral Arteries ◽  
Inhibitory Effect ◽  
Contractile Responses ◽  
Middle Cerebral Arteries ◽  
The Right ◽  
Endothelial Receptor

To clarify the effect of extracellular magnesium (Mg2+) on the vascular reactivity of feline isolated middle cerebral arteries, the effects of slight alterations in the Mg2+ concentration on the contractile and endothelium-dependent dilatory responses were investigated in vitro. The contractions, induced by 10−8-10−5 M norepinephrine, were significantly potentiated at low Mg2+ (0.8 m M v. the normal, 1.2 m M). High (1.6 and 2.0 m M) Mg2+ exhibited an inhibitory effect on the contractile responses. No significant changes, however, in the EC50 values for norepinephrine were found. The endothelium-dependent relaxations induced by 108–10−5 M acetylcholine were inhibited by high (1.6 and 2.0 m M) Mg2+. Lowering of the Mg2+ concentration to 0.8 m M or total withdrawal of this ion from the medium failed to alter the dilatory potency of acetylcholine. The changes in the dilatory responses also shifted the EC50 values for acetylcholine to the right. The present results show that the contractile responses of the cerebral arteries are extremely susceptible to the changes of Mg2+ concentrations. In response to contractile and endothelium-dependent dilatory agonists, Mg2+ probably affects both the calcium influx into the endothelial and smooth muscle cells as well as the binding of acetylcholine to its endothelial receptor. Since Mg2+ deficiency might facilitate the contractile but not the endothelium-dependent relaxant responses, the present study supports a role for Mg2+ deficiency in the development of the cerebral vasospasm.

Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: Inhibitory effect on endothelinA receptor—mediated contraction

2005 ◽  
Vol 102 (6) ◽  
pp. 1101-1107 ◽  
Author(s):  
Hartmut Vatter ◽  
Michael Zimmermann ◽  
Veronika Tesanovic ◽  
Andreas Raabe ◽  
Lothar Schilling ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cerebral Vasospasm ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Affinity Constant ◽  
Dependent Manner ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature. Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2). The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−). Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

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