Human Uterine Artery Research Articles

O–245 - Roles of endogenous NOS inhibitors and ET-1 for the intimai hyperplasia in perimenopausal human uterine arteries.

O–245 - Roles of endogenous NOS inhibitors and ET-1 for the intimai hyperplasia in perimenopausal human uterine arteries.

Endothelium-derived prostanoids reduce 5-hydroxytryptamine-induced contraction in the human uterine artery.

The contribution of endothelium-linked mechanisms to the contraction induced by 5-hydroxytryptamine (5-HT) was investigated in the isolated human uterine artery. 5-HT contracted the uterine artery concentration-dependently. Removal of the endothelium or treatment with the cyclooxygenase inhibitor indomethacin potentiated the contractile response to 5-HT. The nitric oxide synthase inhibitor L-N(G)-monomethyl-arginine (L-NMMA) did not influence the contraction induced by 5-HT. Indomethacin did not affect the response to 5-HT in endothelium-denuded vessels. The 5-HT1 receptor agonist 5-carboxyamidotryptamine (5-CT) did not relax precontracted arteries. Removal of the endothelium did not change the response to 5-HT in the presence of the 5-HT(1B/D) receptor antagonist GR127935 and the 5-HT1A and 5-HT1B receptor antagonist -pindolol. The 5-HT1B receptor antagonist SB224289 did not affect the contraction induced by 5-HT. The results indicate that the 5-HT-induced contraction in the human uterine artery is accompanied by the release of an endothelium-derived relaxing factor (EDRF). This EDRF seems to be a prostanoid, probably prostacyclin (PGI2). The endothelium-linked mechanism seems to be mediated via a 5-HT1 receptor, but it is not possible to further classify the receptor subtype by the information obtained in this study.

Magnesium and cardiovascular disease.

Magnesium and cardiovascular disease.

Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in the human uterine artery.

The influence of pregnancy on the dilator effects of acetylcholine in the isolated human uterine artery was investigated. Acetylcholine (0.1 nM to 0.1 microM) produced concentration- and endothelium-dependent relaxation of norepinephrine (3 microM)-induced contraction. The relaxation was greater in arteries from pregnant patients (P arteries) than from non-pregnant patients (NP arteries). The maximal relaxation was 53.5+/-3.4% (n=21) in P arteries and 23.5+/-2.5% (n=35) in NP arteries. In both P and NP arteries the cholinergic relaxation was increased in the presence of superoxide dismutase and greatly reduced in the presence of the nitric oxide synthase inhibitors, NG-mono-methyl L-arginine (L-NMMA) and L-nitro-arginine-methylester (L-NAME). The effect of these nitric oxide synthase inhibitors was reversed by L-arginine. We conclude that pregnancy enhances acetylcholine-induced nitric oxide synthesis and release in the human uterine artery.

Predominant role for nitric oxide in the relaxation induced by vasoactive intestinal polypeptide in human uterine artery.

It has been previously shown that vasoactive intestinal polypeptide (VIP) induces endothelium-dependent relaxation of the human uterine artery. However, the nature of the mediator of the VIP-induced endothelium-dependent relaxation of the human uterine artery has not yet been determined. Therefore these experiments were undertaken to examine the effects of VIP on human uterine arteries and to establish the role of various endothelial factors on the relaxation induced by VIP. The experiments were performed on isolated human uterine arterial rings. VIP (0.3-100 nM) induced a concentration-dependent relaxation of human uterine arteries with intact endothelium (pEC50 = 8.06+/-0.14, n = 28). After the removal of the endothelium this relaxation was abolished (n = 6). Indomethacin (10 microM), a cyclooxygenase inhibitor, and diethylcarbamazine (100 microM), a lipoxygenase blocker, had no effects on VIP-induced relaxation. In contrast, methylene blue (10 microM), a blocker of guanylate cyclase, NG-monomethyl-L-arginine (10 microM), an inhibitor of nitric oxide (NO) synthase, and 4-aminopyridine (1 mM), a non-selective blocker of K+ channels, antagonized the effect of VIP with suppression of maximal VIP-induced relaxation. Non-competitive antagonism with methylene blue revealed that the pKa value for VIP-receptor complex was 8.10+/-0.10 (n = 6) and the receptor reserve expressed as KA/EC50 was 0.89+/-0.11, where pKa = log10KA, and KA is the dissociation constant of VIP-receptor complex. Therefore, on the basis of the results presented, we can conclude that VIP induces endothelium-dependent relaxation in human uterine arteries, acting as a partial agonist on this blood vessel. It appears that endothelium-dependent relaxation induced by VIP in human uterine artery can be entirely explained by the release of NO from endothelial cells.

Effects of the vasopressin V1a receptor antagonist, SR 49059, on the response of human uterine arteries to vasopressin and other vasoactive substances

Arginine vasopressin (AVP) activates the uterus via V1a receptors and is apparently an important factor for the myometrial hyperactivity, uterine ischemia and pain of primary dysmenorrhea. The orally active and selective, non-peptide AVP1a receptor antagonist, SR 49059, has been shown to inhibit the myometrial action of AVP, but the specific influence of this substance on the effects of AVP and other vasoactive agents on human uterine arteries is unknown. Concentration-responses of AVP on isolated medium-sized human uterine arteries were studied after incubation with only vehicle (DMSO, 0.1%) and with SR 49059 in concentrations of 0.5, 2.5 and 10 nmol/L. Furthermore, the concentration-responses of AVP were investigated without and with SR 49059 (2 and 10 nmol/L) on small and medium-sized arteries. Finally, the influence of 2.5 nmol/L of SR 49059 on concentration-responses of endothelin-1, noradrenaline and prostaglandin F2 alpha was studied. The EC50 for AVP on medium-sized arteries was 0.53 +/- 13 nmol/L. SR 49059 caused a competitive, dose-dependent inhibition of AVP-responses, the highest concentration giving an EC50 of 460 nmol/L. The pA2 value was 9.84. The responses of the small artery preparations to AVP, both without and with the antagonist, were more pronounced than those of the medium-sized ones. The vasoconstrictive effects of endothelin-1, noradrenaline and prostaglandin F2 alpha were less pronounced than those of AVP and unaffected by pre-exposure to SR 49059. The high potency of AVP on human uterine arteries, particularly those of small size, supports an involvement of the peptide in the regulation of uterine blood flow in both physiological and pathophysiological condition. SR 49059 is a potent and selective AVP V1a receptor antagonist in the smooth muscle of human uterine arteries.

A nonradioactive method for localization of endothelin receptor mRNA in situ.

To investigate relationships between the distribution of endothelin (ET) receptor expression and histopathology of heart and blood vessels, we developed a method of nonradioactive in situ hybridization in paraffin sections. Rat mesenteric bed, rat heart, and human uterine artery were fixed in formalin and embedded in paraffin ETA and ETB receptor cDNAs were subcloned into plasmid vectors for synthesis of sense and anti-sense probes. Digoxigenin (DIG)-UTP was incorporated into every twentieth to twenty-fifth nucleotide of the newly transcribed cRNA. mRNA was detected in situ using an anti-DIG alkaline phosphatase antibody and an alkaline phosphatase substrate. In blood vessels, ETA receptor mRNA was localized to the medial smooth muscle layer and ETB receptor mRNA to the endothelial and adventitial layers. Hearts from rats that had undergone coronary artery ligation for induction of CHF showed intense staining for ETB receptor mRNA in the scarred and infarcted zone of the left ventricle. This method provides a suitable alternative to radioisotope-labeled probes for detection of ET receptor mRNA. It allows better preservation of tissues, shorter detection time, and improved morphology for microscopic analysis.

Dual signal transduction by Calcitonin Gene-Related Peptide (CGRP) to relax human uterine arteries

Dual signal transduction by Calcitonin Gene-Related Peptide (CGRP) to relax human uterine arteries

Effects of the vasopressin V1areceptor antagonist, SR 49059, on the response of human uterine arteries to vasopressin and other vasoactive substances

Effects of the vasopressin V_1areceptor antagonist, SR 49059, on the response of human uterine arteries to vasopressin and other vasoactive substances

2.P.309 Effects of female sexual hormones on contractility and morphology of pre- and postmenopausal human uterine arteries

2.P.309 Effects of female sexual hormones on contractility and morphology of pre- and postmenopausal human uterine arteries

Effects of menidipine and nifedipine on isolated human uterine artery rings: Z.-Y. Guo; M.-R. Rao Chin Pharmacol Bull 1996 12/3 (262–264)

International Journal of Gynecology & ObstetricsVolume 58, Issue 2 p. 263-263 Citations from the chinese literature Effects of menidipine and nifedipine on isolated human uterine artery rings Z.-Y. Guo; M.-R. Rao Chin Pharmacol Bull 1996 12/3 (262–264) First published: 14 January 1998 https://doi.org/10.1016/S0020-7292(97)89848-7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume58, Issue2August 1997Pages 263-263 RelatedInformation

Effect of oxytocin as a partial agonist at vasoconstrictor vasopressin receptors on the human isolated uterine artery.

1. The effect of oxytocin on endothelium-intact and endothelium-denuded segments of the human uterine artery rings was investigated. 2. In both types of preparation oxytocin induced contraction of human uterine artery with similar potency and efficacy (pEC50 values: 6.95 +/- 0.05 vs 7.06 +/- 0.01; maximal response values: 61 +/- 4.1% vs 63 +/- 5.1% for arteries with and without endothelium, respectively). 3. In contrast, human uterine arteries, both intact and denuded of endothelium, did not respond to the addition of the selective oxytocin receptor agonist, [Thr4, Gly7]oxytocin (10 nM(-1) microM). 4. The vasopressin receptor antagonists, [d(CH2)5Tyr(Me)]AVP (10-100nM) and [d(CH2)5,D-Ile2,Ile4]AVP (300 nM-3 microM) produced parallel rightward shifts of the curves for oxytocin. The Schild plots constrained to a slope of unity gave the following -log K(B) values: [d(CH2)5Tyr(Me)] AVP vs [d(CH2)5,D-Ile2,Ile4] AVP 9.24 vs 6.91 and 9.26 vs 6.84 for human uterine artery with intact and those denuded of endothelium, respectively. In contrast, in both types of preparations the oxytocin receptor antagonist, [d(CH2)5Tyr(OMe), 2Orn8]vasotocin (1 microM), did not significantly affect oxytocin-induced contractions. 5. The calculated pK(A) values for oxytocin itself also did not differ between preparations: 6.56 and 6.43 for human uterine artery with and without endothelium, respectively. In both types of preparations, the receptor reserve (K(A)/EC50) was close to unity (intact vs denuded: 3.9 vs 3.0). 6. It is concluded that, in human uterine artery, oxytocin induces contractions that are not modulated by the endothelium. It is likely that oxytocin acts as a partial agonist on human uterine artery, regardless of the endothelial condition. On the basis of differential antagonists affinity and affinity of oxytocin itself, it is probable that receptors involved in oxytocin-induced contraction in human uterine arteries belong to the V(1A) vasopressin receptors.

The effect of nitric oxide on uterine and umbilical artery flow velocity waveform in pre-eclampsia

We compared the flow velocity waveforms of uterine and umbilical arteries in normotensive and pre-eclamptic patients at mid-gestation. In a randomised controlled trial we tested the effects of isosorbide dinitrate (ISDN, nitric oxide donor) patch therapy on the flow velocity waveform of pre-eclamptic patients at mid-gestation. The resistance indices (RI) of human uterine and umbilical arteries were higher in pre-eclamptic patients compared to the normotensive patients. ISDN patch therapy significantly reduced the increased RI values of the umbilical artery in pre-eclamptic patients without any change in systemic blood pressures, but the RI values of the uterine artery were not significantly attenuated. The change in RI values of the umbilical artery might be due to the improvement of end-diastolic flow velocity. These results suggest that the feto-placental circulation is impaired in pre-eclampsia, perhaps due to the disturbance of the endothelium-dependent vaso-relaxation system, and that ISDN therapy may improve the impaired endothelium dependent nitric oxide system.

5-Hydroxytryptamine contracts human uterine artery smooth muscle predominantly via 5-HT2 receptors.

Serotonergic receptors were classified in the isolated human uterine artery with intact endothelium, using agonists and antagonists for 5-hydroxytryptamine (5-HT) receptors. The efficacy for different agonists rated: alpha-methyl-5-HT (5-HT2) = 5-HT (non-selective) = 2-methyl-5-HT (5-HT3) >> sumatriptan (5-HT1), and the potency as: sumatriptan = 5-HT > 5-HT > alpha-methyl-5-HT > 2-methyl-5-HT. The contractile effects of 5-HT and alpha-methyl-5-HT were antagonized by the 5-HT2 receptor antagonist ketanserin and the non-selective antagonist methiothepin. The efficacy of sumatriptan was comparatively low. No interaction was encountered between 2-methyl-5-HT and MDL72222, suggesting an absence of 5-HT3 receptors. The results indicate that the contractile serotonergic receptor population in the human uterine artery mainly comprises 5-HT2 receptors, although a minor contribution of contractile 5-HT1 receptors cannot be excluded.

Potent inhibition by tamoxifen of spontaneous and agonist-induced contractions of the human myometrium and intramyometrial arteries

OBJECTIVE: Our purpose was to elucidate the mechanism of direct (nongenomic) action of antiestrogens on spontaneous and agonist-induced contractions of the human myometrium and uterine arteries. STUDY DESIGN: Myometrial strips and pieces of uterine arteries were obtained from nonpregnant premenopausal women undergoing hysterectomy. Spontaneous activity of myometrium and responses of myometrium and artery to K +-depolarization and vasopressin were recorded under isometric conditions. Quantification of the responses was done by planimetry. RESULTS: The 50% inhibitory concentration values for tamoxifen, clomiphene, and cyclofenil in the case of myometrial spontaneous activity were 2.8, 43, and 331 nmol/L, respectively. Vasopressin-induced contractions in both the myometrium and arteries were potently inhibited by tamoxifen, and the 50% inhibitory concentration for the myometrium (1.4 nmol/L) was significantly lower ( p < 0.05) than that for the arteries (11 nmol/L). Although tamoxifen caused no inhibition of responses induced by high potassium chloride (80 mmol/L), responses induced by low potassium chloride (20 mmol/L) were inhibited by 40% to 50% in both the myometrium and arteries. Glibenclamide reversed the inhibition by tamoxifen of spontaneous myometrial activity. CONCLUSIONS: Tamoxifen is a highly potent inhibitor of the contractile activity of the human nonpregnant myometrium and uterine arteries. It is suggested that tamoxifen could have strong potential in the treatment of dysmenorrhea. (Am J Obstet Gynecol 1997;176:381-6.)

Early ultrasound diagnosis and follow-up of molar pregnancies.

The objective of this study was to investigate the role of ultrasound in the differential diagnosis and management of early pregnancies presenting with placental molar changes. Placental features were recorded over a 10-month period in women undergoing ultrasound examination at 10-14 weeks of gestation. In cases of a molar pregnancy, the fetal karyotype was obtained in utero and, if the pregnancy continued, the maternal concentration of human chorionic gonadotropin (hCG) and uterine artery resistance to flow were measured serially. A histopathological examination of the placenta was performed in all cases after delivery. During the study period, 9425 women had an early scan and 11 molar pregnancies were identified including one classical mole, four hydatidiform moles coexisting with a normal pregnancy, three partial triploid moles and three partial moles associated in one case with a fetus presenting congenitial anomalies diagnostic of Beckwith-Wiedemann syndrome. The hCG levels were high in all cases except one case of triploidy and remained high during the rest of the pregnancy in cases of hydatidiform moles coexisting with a fetus. In these cases, the uterine artery resistance was normal. The present data indicate that placental ultrasound examination can correctly identify molar changes in early pregnancy and together with hCG level and uterine Doppler measurements can establish the differential diagnosis in utero of the various forms of placental molar transformations.

O-9 - Impaired synergism between PGh and NO leads to the intimai hyperplasia in premenopausal human uterine arteries

O-9 - Impaired synergism between PGh and NO leads to the intimai hyperplasia in premenopausal human uterine arteries

Intimal hyperplasia in human uterine arteries accompanied by impaired synergism between prostaglandin I2 and nitric oxide.

1. The present experiments were designed to investigate the mechanisms causing intimal hyperplasia in connection with the impaired synergism between prostaglandin I2 (PGI2) and nitric oxide (NO) in human uterine arteries (UAs). 2. In order to assess the magnitude of intimal hyperplasia, the intima:media ratio (%) was estimated with the aid of an image analyser. Human UAs were classified into two groups, I and II on the basis of the ratio and the degree of elastin deposition of histologically normal specimens. The intima:media ratio in group II was determined to be 38.9 +/- 7.7% (n = 6), which was significantly (P < 0.01) higher than that in group I (16.5 +/- 1.5%, n = 7). Less deposition of elastin was found in group I than in group II. 3. The relaxation activities of iloprost (IP) as a stable analogue of PGI2 and sodium nitroprusside (SNP) as a NO donor were not different between the two groups. When the minimum concentrations (Cmin) of IP and SNP in producing relaxation were applied together to the UA strips, these compounds interacted synergistically in group I. The observed relaxation (48.7 +/- 8.8%, n = 7) in this group was significantly (P < 0.01) greater than the predicted value of 18.8 +/- 3.1% (n = 7) (the mathematical sum of the relaxations caused by IP and SNP alone). By contrast, these agents interacted in an additive manner in group II. The observed relaxation (20.8 +/- 9.5%, n = 6) was not significantly different from the predicted value (18.6 +/- 2.4%, n = 6) in this group. 4. During the relaxation produced by the addition of IP and SNP alone or in combination, the changes in cyclic nucleotides (cyclic AMP and cyclic GMP) contents (pmol mg-1 protein) were assayed. When IP and SNP at Cmin were applied together to the UA strips, these compounds interacted synergistically in increasing cyclic nucleotides in group I. The observed net increase in the content was determined to be 1.46 +/- 0.30 (P < 0.05 vs. the predicted value of 0.67 +/- 0.12) in this group (n = 7). By contrast, the observed net increase (0.40 +/- 0.07, n = 6) did not exceed the predicted value (0.65 +/- 0.07, n = 6) in group II. 5. These results suggest that the formation of intimal hyperplasia in group II may be closely related to the impaired synergism between PGI2 and NO in the human UAs.

P099 Background of aging change in arterial wall: Intimal hyperplasia with the impaired synergism between PG12 and nitric oxide in human uterine arteries before menopause

P099 Background of aging change in arterial wall: Intimal hyperplasia with the impaired synergism between PG12 and nitric oxide in human uterine arteries before menopause

Effects of adenyl purines in human uterine arteries and uterine myometrium.

This in vitro study was undertaken to investigate the effects of adenyl purines in human uterine myometrium and uterine arteries. Segments of uterine myometrium and uterine arteries obtained at hysterectomy were isolated and mounted in tissue chambers. The muscle activity was recorded by polygraph. Adenyl purines agonists, such as adenosine, N-[(R)-1-methyl-2 phenylethyl]-adenosine (R-PIA) and 5-N-ethylcarboxamide adenosine (NECA) produced concentration-dependent contraction in human uterine myometrium. The potency order was NECA = R-PIA > adenosine. Adenosine A1 receptor antagonist: 1, 3-dipropyl-8-cyclopentylxanthine (DPCPX) blocked the effect of adenosine in human uterine myometrium. Otherwise, adenyl purines induced dose-dependent relaxation in human uterine artery precontracted by phenylephrine (PE, 10(-5)M). The potency gradient was NECA > R-PIA > adenosine; the results indicate adenyl purine induces uterine myometrium contraction via A1 receptor. However, adenosine causes uterine artery relaxation by A2 receptor.