Supersensitivity to the stimulant action of noradrenaline on human myometrium near term

1993 ◽  
Vol 5 (1) ◽  
pp. 39 ◽  
Author(s):  
JN Pennefather ◽  
JD Paull ◽  
ME Story ◽  
SP Ziccone

Noradrenaline (10-50 nM) and tyramine (0.05-1 mM) enhanced contractile force elicited by field stimulation of strips of myometrium from non-pregnant and pregnant women. In higher concentrations, noradrenaline produced sustained contractions. The EC50 values for noradrenaline were 0.4 microM in tissues from pregnant women and 3.1 microM in tissues from non-pregnant women; maximum responses were greater in the former tissues. In addition, the effects of noradrenaline on myometrium from pregnant women were more marked on the inner layer than on the outer layer, antagonized by the alpha 1-adrenoceptor antagonist prazosin (0.1 and 1.0 microM), and unaffected by the inhibitor of neuronal uptake, nisoxetine (0.1 microM). Taken together, these observations confirm that supersensitivity to noradrenaline develops during pregnancy and is present near term. The supersensitivity to noradrenaline at term can be attributed only in part to a decrease in its removal by the sympathetic innervation, which declines towards term, because responses to tyramine were also enhanced in tissues from pregnant women. It is possible that gap junction formation may also contribute to this supersensitivity.

2009 ◽  
Vol 296 (4) ◽  
pp. C766-C782 ◽  
Author(s):  
Sharon Tsang ◽  
Stanley S. C. Wong ◽  
Song Wu ◽  
Gennadi M. Kravtsov ◽  
Tak-Ming Wong

We hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both α1- and β1-adrenoceptors by increasing Ca2+ release from the sarcoplasmic reticulum (SR) and speedier removal of Ca2+ from cytosol via Ca2+-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 μg/100 g body wt) in the presence of norepinephrine (10−7 M), the α1-adrenoceptor agonist phenylephrine (10−6 M), or the nonselective β-adrenoceptor agonist isoprenaline (10−7 M) in the presence of 5 × 10−7 M ICI-118,551, a β2-adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca2+ concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca2+ release via the ryanodine receptor (RyR) or releasable Ca2+ in the SR, in ventricular myocytes isolated from the three groups of rats. We also measured 45Ca2+ release via the RyR. We then determined the time to 50% decay of both transients, which represents, respectively, Ca2+ reuptake by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and removal via the sarcolemmal Na+/Ca2+ exchanger (NCX). We correlated Ca2+ removal from the cytosol with activities of SERCA and its regulator phospholamban as well as NCX. The results showed that testosterone at physiological levels enhanced positive inotropic and lusitropic responses to stimulation of α1- and β1-adrenoceptors via the androgen receptor. The increased contractility and speedier relaxation were associated with increased Ca2+ release via the RyR and faster Ca2+ removal out of the cytosol via SERCA and NCX.


Reproduction ◽  
2005 ◽  
Vol 129 (4) ◽  
pp. 525-530 ◽  
Author(s):  
Xilian Bai ◽  
George J Bugg ◽  
Susan L Greenwood ◽  
Jocelyn D Glazier ◽  
Colin P Sibley ◽  
...  

Two-pore domain K+channels are an emerging family of K+channels that may contribute to setting membrane potential in both electrically excitable and non-excitable cells and, as such, influence cellular function. The human uteroplacental unit contains both excitable (e.g. myometrial) and non-excitable cells, whose function depends upon the activity of K+channels. We have therefore investigated the expression of two members of this family, TWIK (two-pore domain weak inward rectifying K+channel)-related acid-sensitive K+channel (TASK) and TWIK-related K+channel (TREK) in human myometrium. Using RT-PCR the mRNA expression of TASK and TREK isoforms was examined in myometrial tissue from pregnant women. mRNAs encoding TASK1, 4 and 5 and TREK1 were detected whereas weak or no signals were observed for TASK2, TASK3 and TREK2. Western blotting for TASK1 gave two bands of approximately 44 and 65 kDa, whereas TREK1 gave bands of approximately 59 and 90 kDa in myometrium from pregnant women. TASK1 and TREK1 immunofluorescence was prominent in intracellular and plasmalemmal locations within myometrial cells. Therefore, we conclude that the human myometrium is a site of expression for the two-pore domain K+channel proteins TASK1 and TREK1.


2017 ◽  
pp. 71-73
Author(s):  
N.Yu. Bysaha ◽  

The objective: study of hormonal status in pregnant women with benign cervical pathology (CP) in anamnesis. Patients and methods. Clinical and statistical analysis of the hormonal status of 100 women with a history of benign CP pathology has been performed. According to the revealed symptoms of CP during colposcopic examination, women were divided into two groups: 100 pregnant women, in whom colposcopic and cytologically signs of CP pathology were not detected, were included in the control group; and 100 women who had a pathology of CP, entered the main group. Results. The study examined hormonal relationships in the system mother–placenta–fetus, namely the level of hormones such as estriol, progesterone, human chorionic gonadotropin, placental lactogen. Hormonal changes in pregnant women and contribute to reducing the immunoreactivity unwanted stimulation of existing benign hyperplastic background processes in the cervix. Conclusion. Determining functional state placenta is an important factor in the timely diagnosis of disorders in the functioning of the system mother–placenta–fetus. Key words: hormonal status, placenta, uterine cervix, fetoplacental complex.


Author(s):  
Linda M Biesty ◽  
Aoife M Egan ◽  
Fidelma Dunne ◽  
Valerie Smith ◽  
Pauline Meskell ◽  
...  

2000 ◽  
Vol 279 (3) ◽  
pp. H1201-H1207 ◽  
Author(s):  
Masato Tsuboi ◽  
Yasuyuki Furukawa ◽  
Koichi Nakajima ◽  
Fumio Kurogouchi ◽  
Shigetoshi Chiba

Some parasympathetic ganglionic cells are located in the epicardial fat pad between the medial superior vena cava and the aortic root (SVC-Ao fat pad) of the dog. We investigated whether the ganglionic cells in the SVC-Ao fat pad control the right atrial contractile force, sinus cycle length (SCL), and atrioventricular (AV) conduction in the autonomically decentralized heart of the anesthetized dog. Stimulation of both sides of the cervical vagal complexes (CVS) decreased right atrial contractile force, increased SCL, and prolonged AV interval. Stimulation of the rate-related parasympathetic nerves to the sinoatrial (SA) node (SAPS) increased SCL and decreased atrial contractile force. Stimulation of the AV conduction-related parasympathetic nerves to the AV node prolonged AV interval. Trimethaphan, a ganglionic nicotinic receptor blocker, injected into the SVC-Ao fat pad attenuated the negative inotropic, chronotropic, and dromotropic responses to CVS by 33∼37%. On the other hand, lidocaine, a sodium channel blocker, injected into the SVC-Ao fat pad almost totally inhibited the inotropic and chronotropic responses to CVS and partly inhibited the dromotropic one. Lidocaine or trimethaphan injected into the SAPS locus abolished the inotropic responses to SAPS, but it partly attenuated those to CVS, although these treatments abolished the chronotropic responses to SAPS or CVS. These results suggest that parasympathetic ganglionic cells in the SVC-Ao fat pad, differing from those in SA and AV fat pads, nonselectively control the atrial contractile force, SCL, and AV conduction partially in the dog heart.


1981 ◽  
Vol 240 (4) ◽  
pp. H650-H658 ◽  
Author(s):  
E. Tomomatsu ◽  
K. Nishi

Effects of electrical stimulation of sympathetic nerves to the carotid sinus on the discharge of single active baroreceptor fibers of the rabbit were examined in situ and in functionally isolated carotid sinus preparations with an intact sympathetic innervation under controlled conditions of pressure and temperature. Among 30 single units, 18 units responded to sympathetic stimulation of increasing discharge frequency. The excitatory effect of sympathetic stimulation on baroreceptor activity was not abolished by phentolamine (1 mg/kg iv or 10(-6) g/ml in perfusate). In isolated carotid sinus preparations perfused with Krebs-Henseleit solution, various pressure steps were applied to the sinus, and effects of norepinephrine (NE; 10(-9) and 10(-6) g/ml) on activity of nine single baroreceptor units were examined. In the presence of 10(-9) g/ml NE, discharge frequency of all units significantly increased at a given pressure step when compared with the control, whereas NE at a high concentration (10(-6) g/ml) did not produce significant changes in the discharge frequency. It is concluded that NE released by sympathetic nerve endings most likely acts directly on the baroreceptor nerve endings and sensitizes them.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
F. Füeg ◽  
S. Santos ◽  
C. Haslinger ◽  
B. Stoiber ◽  
L. Schäffer ◽  
...  

Abstract Background Oxytocin receptor (OXTR) gene variants have been shown to affect the prevalence of preterm birth, mode of delivery and oxytocin (OXT) requirements for labor induction and augmentation. We hypothesized that this might be associated with different myometrium responses to oxytocin. Our aim was to investigate the influence of a selection of eight OXTR gene single nucleotide variants on oxytocin-induced stimulation of human myometrium contractility in vitro. Methods Human myometrium biopsies were collected during elective cesarean sections at term, if patients had given informed consent. Myometrial strips were submerged under tension in an organ bath and allowed to contract; the remaining material was stored at − 80 °C for further determination of relevant genetics and mRNA level. The area under the curve (AUC) of all contractions taking place in the absence of OXT and of those occurring upon OXT addition (for 30 min each) was measured. OXT stimulation, defined as the ratio between AUC measurements after OXT addition and those in the absence of OXT was calculated for each strip. TaqMan™ Assays were used to detect the allele distribution of the eight OXTR variants and to determine the relative amounts of OXTR-mRNA in the samples. For each variant, oxytocin stimulation of contractility was compared between samples homozygous for the reference allele (reference group) and samples with at least one variant allele (variant group) by linear regression. Results Sixty samples were included in the present study. For rs1042778, rs11706648, rs4686301, rs53576, rs237895, and rs237902, OXT stimulation was similar in the reference and in the variant groups. However, the values of OXT stimulation differed significantly between the reference and the variant groups for rs4686302 (3.1 vs. 4.1 times; p = 0.022) and rs237888 (3.2 vs. 5.5 times; p = 0.001). No significant differences between the levels of OXTR-mRNA in the various reference and corresponding variant groups were detected. Conclusions Patients with variant alleles of rs237888 and/or rs4686302 may be more sensitive to oxytocin stimulation, explaining why these sequence variants have been associated with lower cesarean section prevalence and premature birth, respectively.


1975 ◽  
Vol 228 (1) ◽  
pp. 141-148 ◽  
Author(s):  
JA Armour ◽  
WC Randall ◽  
S Sinha

Direct electrical excitation of small cardiac branches from the thoracic vagus elicited highly localized and differential responses from individualized segments of the myocardium. For example, small nerves from the vagus at the level of the superior pulmonary veins frequently induced moderate inhibition in contractile force of the ipsilateral atrium with little or no influences elsewhere. Branches from more rostral levels of the thoracic vagus induced changes in atrial contractility, with or without changes in sinoauricular (SA) nodal discharge rates, and often with partial or complete artioventricular (AV) nodal blockade.Excitation of individual, small vagal branches sometimes initiated acceleration in artrial rate and augmentation in atrial contractile force concurrently with complete AV nodal blockade. The negative dromotropic response was eliminated by atropine, leaving only the positive chronotropic and inotropic changes, thus revealing the intermingling of both sympathetic and parasympathetic components even in these small branches. There are frequently in excess of 20 small branches from the vagal trunk between the level of the caudal cervical ganglion and the superior pulmonary vein on each side which will induce highly selective changes in cardiac function upon stimulation. Inhibitory branches are particularly concentrated in the region of the recurrent laryngeal nerve on either side.


1985 ◽  
Vol 248 (2) ◽  
pp. R263-R269 ◽  
Author(s):  
P. J. Goadsby ◽  
R. D. Piper ◽  
G. A. Lambert ◽  
J. W. Lance

The dorsal raphe nucleus (DRN) and surrounding midbrain of 74 cats were stimulated both electrically and chemically, and carotid flows were measured with electromagnetic flow probes. Stimulation of the DRN caused a frequency-dependent decrease in common carotid vascular resistance, which was abolished by bilateral section of the facial nerve intracranially. Injection of DL-homocysteic acid into the DRN reproduced the effect of electrical stimulation, indicating that the responses arose from excitation of cell bodies within the DRN, not from fibers of passage. The responses were mediated entirely within the brain stem since they remained intact after high spinal cord section. The vasodilator response was blocked by the intravenous administration of the nicotinic ganglion blocker hexamethonium but not by the alpha-adrenoceptor blocker phentolamine. The responses were unaffected by intravenous administration of methysergide but were markedly reduced after depletion of central serotonin by pretreatment with the serotonin depletor, p-chlorophenylalanine. A poststimulus constrictor response was mediated by release of catecholamines from the adrenal medulla and was blocked by the alpha-adrenoceptor antagonist phentolamine. No response involved supracollicular mechanisms since they persisted after decerebration.


1983 ◽  
Vol 244 (1) ◽  
pp. C110-C114 ◽  
Author(s):  
C. O. Lee ◽  
M. Vassalle

The actions of norepinephrine and high calcium on the electrical, mechanical, and intracellular sodium ion activities were studied in electrically driven canine cardiac Purkinje fibers under different conditions. It was found that norepinephrine and high calcium decrease intracellular sodium ion activity (aiNa). The exposure to either agent is followed by a transient decline of force that correlates with the lower aiNa. Inhibition of the Na+ -K+ pump by strophanthidin reduces or abolishes the decrease in aiNa by norepinephrine but not that by high calcium. It is concluded that norepinephrine and high calcium both decrease aiNa and thereby the contractile force but (unlike high calcium) norepinephrine acts through the stimulation of the Na+ -K+ pump.


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