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This study investigated the clinical outcomes for patients with pelvic ultrasound findings suspicious for uterine arteriovenous malformations (AVMs) at a single institution. We reviewed the electronic medical record to identify women with pelvic ultrasound reports read as possible uterine AVM, and used medical records to determine clinical outcomes. Among the 39 women with ultrasounds suspicious for AVM, 14 had subsequent MRIs, 10 had additional ultrasounds, and 10 underwent pelvic angiography. Five of the 39 women were ultimately diagnosed with AVMs. Of the 34 women who did not have an AVM, 12 were diagnosed with retained products of conception. Women may be receiving overtreatment for possible uterine AVMs; careful clinical consideration is warranted as the most common clinical diagnosis for women with radiologic findings suspicious of uterine AVM is retained products of conception.Impact statement What is already known on the subject: An acquired uterine arteriovenous malformation (AVM) is an abnormal arterio-venous connection in the myometrium that may cause life-threatening haemorrhage. Over the past decade, it has been noted that the characteristic ultrasound findings of uterine AVM may represent other causes of uterine hypervascularity including retained products of conception. What the results of this study add: As there is no consensus on the management of highly vascular myometrial lesions suspicious for uterine AVMs, this study reports our institution's experience with pelvic ultrasound findings suspicious for uterine AVMs. We found that further diagnostic workup, including MRI and angiography were common, but that the most frequent final diagnosis was retained products of conception. What the implications are of these findings for future clinical practice: This study contributes to the growing body of work noting spectrum of conditions with similar vascular ultrasound findings, and suggests that at least in this sample, women may be receiving overtreatment for these presumed uterine AVMs. Close collaboration among gynaecologists and radiologists is needed to interpret the significance of these radiographic images and to determine the appropriate intervention, as women with radiologic findings suspicious of uterine AVM will frequently have retained products of conception.

We present our initial experience of using the HDlive Flow silhouette mode to construct images of two cases of uterine enhanced myometrial vascularity/arteriovenous malformations (EMV/AVMs). In the first case, the HDlive Flow silhouette mode clearly depicted a fused vascular tumor with irregular contour in the posterior myometrium. In the second case, a large hypervascular mass occupying the entire fundal lesion of the uterus was clearly identified using the HDlive Flow silhouette mode. Moreover, spatial relationships among the hypervascular mass, intrauterine blood collection, and dilated, spiral-shaped right uterine artery enabled the clear localization of the mass. The HDlive Flow silhouette mode provides a novel, unique sonographic image of uterine EMV/AVMs, and might facilitate their diagnosis and localization in the myometrium.

Uterine leiomyomata present major problem for females. Although they are benign tumors their frequency is associated with many symptoms like infertility, abdominal pain, menorrhagia. Authors based on their own morphological studies and review of the literature try to indicate main factors causing angiogenesis within leiomyomata and its influence on tumor growth. The strongest proangiogenic factor seems to be hypoxia, which stimulates up- and down-regulation of numerous genetically determined substances. Also mechanical pressure acting upon newly growing vessels is one of the factors which may determine formation of so called "vascular pseudocapsule" around the lesion.

The uterus plays an essential role in mammalian reproduction and is a target of several hormonal protocols used to improve fertility in cattle. Many studies highlighted the importance of eCG treatment following fixed-time artificial insemination in improving follicular growth, ovulation and pregnancy rates in cattle. Moreover, eCG has been implicated in angiogenesis, leading to important changes in uterine blood flow and vascularisation. However, there is still a lack of information regarding the specific alterations induced by eCG upon glandular and vascular characteristics of bovine uterus. To investigate the influence of eCG on: uterine thickness and area; uterine artery diameter and area; uterine vascular and gland density; and the expression of the VEGFA-system, the uteri of crossbred beef cows were collected. All cows were submitted to follicular wave emergence synchronization. On day four of protocol, cows submitted to superovulation (n = 6) received 2000 IU eCG, on day eight, after expected follicular deviation, cows submitted to stimulatory treatment (n = 5) received 400 IU eCG. Control cows (n = 5) did not receive eCG. On day five po cows were subjected to ultrassonographic evaluation and slaughtered for uterine tissue sampling on day six po. Uterine vessels and glands were quantified by the counting point stereological method. The VEGFA-system was localized in different cellular types, showing no qualitative or quantitative differences in the site of expression or the intensity of the positive signal among the groups. Vascular density was decreased in the endometrium of stimulated and myometrium of superovulated cows compared with the control ones, which showed higher vascular density in the myometrium and endometrium of the ipsilateral uterine horn. The uterine gland density was higher in superovulated compared with stimulated and control cows. Thus, we can infer that stimulatory or superovulatory treatments with eCG influence the vascular density in the endometrium and myometrium in cattle., (© 2014 Blackwell Verlag GmbH.)

During pregnancy the mammalian uterine circulation undergoes significant expansive remodelling necessary for normal pregnancy outcome. The underlying mechanisms are poorly defined. The goal of this study was to test the hypothesis that myometrial stretch actively stimulates uterine vascular remodelling by developing a new surgical approach to induce unilateral uterine distension in non-pregnant rats. Three weeks after surgery, which consisted of an infusion of medical-grade silicone into the uterine lumen, main and mesometrial uterine artery and vein length, diameter and distensibility were recorded. Radial artery diameter, distensibility and vascular smooth muscle mitotic rate (Ki67 staining) were also measured. Unilateral uterine distension resulted in significant increases in the length of main uterine artery and vein and mesometrial segments but had no effect on vessel diameter or distensibility. In contrast, there were significant increases in the diameter of the radial arteries associated with the distended uterus. These changes were accompanied by reduced arterial distensibility and increased vascular muscle hyperplasia. In summary, this is the first report to show that myometrial stretch is a sufficient stimulus to induce significant remodelling of uterine vessels in non-pregnant rats. Moreover, the results indicate differential regulation of these growth processes as a function of vessel size and type.

Purpose: The purpose of this article was to investigate clinical ultrasonographic findings and the outcomes of post-pregnancy patients with acquired uterine vascular abnormalities including arteriovenous malformations (AVMs)., Materials and Methods: We performed a computerized database search for all patients with ultrasonographic findings of a vascular abnormality including AVM in our referral center between 2000-2008. An ultrasound finding of vascular abnormality was defined as an area of strong hypervascularity within the myometrium and the presence of marked turbulence. The inclusion criteria for angiography were abnormal vaginal bleeding in a hemodynamically stable patient, bhCG serum levels ≤ 30 mIU/ml, and ultrasound demonstration of large (≥ 15 mm on the larger side of the vessel) or multiple vascular lesions., Results: 16 women were identified, of whom 10 (63 %) underwent uterine artery embolization. Angiography confirmed the pre-interventional ultrasound diagnosis of AVM in all cases. AVM feeding arteries were on the left side of the uterus in 80 % of the cases. Residual tissue was ultrasonographically detected in five patients: 2 underwent hysteroscopy and guided curettage following embolization and three received methotrexate. All tissue samples were benign. One small vascular abnormality resolved spontaneously., Conclusion: An acquired uterine vascular abnormality including AVM should be considered in the work-up of post-pregnancy vaginal bleeding., (© Georg Thieme Verlag KG Stuttgart · New York.)

Proliferation, differentiation, and apoptosis are three major processes by which the pregnant uterus maintains homeostasis to accommodate the growing fetus. We demonstrated previously that caspase activation in the pregnant rat myometrium at midgestation coincides with the transition from uterine hyperplasia to hypertrophy. We hypothesized that this transition was induced by stasis of myometrial blood flow (and subsequent hypoxia/ischaemia insult) resulting from acute myometrial stretch induced by a growing embryo. Therefore, we measured the expression of active caspase 3 and two hypoxia markers (transcription factor HIF1A and pimonidazole hydrochloride) in pregnant rat myometrium. To investigate the effect of gravidity we used unilaterally pregnant rats. Caspase 3 was activated only in the gravid horn of the unilaterally pregnant animals on Gestational Days 12-15. This activation was associated with high levels of HIF1A and pimonidazole immunostaining, which were limited to the circular myometrial layer of the gravid horn, indicative of hypoxia within this tissue. To isolate the effect of myometrial stretch applied by the growing fetus, we inserted an expandable polymer tube (intra-uterine expandable tube [IUET]) into the empty horn of Day 13 and Day 20 unilaterally pregnant rats. Tissue was collected 2, 14, and 24 h later. In the IUET-stretched empty horn, cleaved caspase 3 was activated at midgestation (Day 14), but not at late gestation (Day 21). We speculate that hypoxia resulting from mechanical stretch may activate caspase 3 within the pregnant myometrium only in the context of a specific endocrine environment.

While there is a growing realization that the origins of major obstetrical complications associated with defective deep placentation, such as pre-term labour, fetal growth restriction and pre-eclampsia, may lie in the very early pregnancy events, the underlying mechanisms are not understood. Impaired deep placentation is foremost a vascular pathology, characterized by a lack of endovascular trophoblast invasion and remodelling of a segment of the spiral arteries embedded within the inner myometrium of the uterus. Outside pregnancy, the inner myometrium represents a highly specialized, hormone-dependent structure, termed the junctional zone (JZ), which plays an integral part in the implantation process. The JZ changes with age and is disrupted in several reproductive disorders, such as endometriosis and adenomyosis, which in turn may account for the increased risk of adverse pregnancy outcome. Unlike the endometrium, the myometrial JZ is not readily accessible to biochemical or molecular studies, yet its structure and function can be assessed using imaging techniques, such as high-resolution ultrasound and magnetic resonance imaging. Thus, non-invasive assessment of the JZ prior to conception may turn out to be useful in identifying those women at risk of major obstetrical complications.

Purpose: To evaluate the hemodynamic changes by transvaginal color Doppler sonography (CDS) in the uterine vascular bed after the insertion of a contraceptive intrauterine device (CIUD) and to investigate whether those CDS findings could predict potential side effects, such as dysmenorrhea and abnormal bleeding., Method: Pulsatility index (PI), resistance index, and systole/diastole ratio (S/D) were measured in the uterine artery and its myometrial branches on 28 patients before and after the insertion of copper IUD, and a correlation with dysmenorrhea and abnormal bleeding was investigated., Result: PI and S/D values in the uterine artery increased significantly after the insertion of the CIUD (p < 0.05). Patients with increased bleeding scores after insertion of CIUD had significantly lower uterine artery PI compared with those without increased bleeding scores (p < 0.05). No statistically significant difference was detected in the Doppler flow parameters regarding dysmenorrhea scores., Conclusion: Low uterine artery PI values recorded in the early phase of the menstrual cycle in patients with a CIUD were associated with an increased bleeding risk., ((c) 2009 Wiley Periodicals, Inc.)

Objective: The aim of this study was to investigate the incidence and causes of uterine hypervascular lesions showing low-impedance, high-velocity flow on color Doppler sonography (CDS) after first-trimester dilation and curettage (D&C)., Methods: This was a prospective study of 65 consecutive women who underwent first-trimester termination of pregnancy. Color Doppler sonography of the uterus was performed on days 3 and 10 after D&C. If the myometrial hypervascularity (MH) persisted on day 10, a second D&C was performed, and then the patients were followed with weekly Doppler examinations., Results: In 16 of 65 women (24.6%), MH was detected with CDS on day 3 after D&C. In 3 cases, MH resolved spontaneously by postabortion day 10. In the remaining 13 patients, the second D&C performed on day 10 revealed retained products of conception (RPOC) in 8 patients (61.5%), a hydatidiform mole in 2 (15.4%), endometritis in 1 (7.7%), and no abnormality in 2 (15.4%). Complete resolution of the MH occurred in all cases. The mean period to the resolution of MH after the second D&C +/- SD was 16.54 +/- 11.06 days (range, 7-48 days). Univariate analysis revealed that gestational age at D&C (P = .012) and a history of any uterine surgery (P = .044) were significantly associated with postabortion MH. On binary logistic regression analysis, gestational age at D&C was the only independent predictive factor for MH (P = .016; odds ratio, 1.47; 95% confidence interval, 1.08-2.02)., Conclusions: The presence of hypervascular areas within the myometrium is a common finding in the postabortion period, and in most cases, the cause of this finding is RPOC.

Objective: This study was undertaken to study vascular reactivity of small myometrial arteries in women with idiopathic menorrhagia., Study Design: Small myometrial arteries were isolated from 6 patients with idiopathic menorrhagia and 4 controls. The contractile responses to thromboxane mimetic (U46619) and endothelin-1 were assessed before and after incubation with N(w)-nitro-L arginine methyl ester alone or in combination with indomethacin (Indo). Endothelium-dependent dilation to bradykinin and basal tension were compared before and after incubation with N(w)-nitro-L arginine methyl ester alone, or with N(w)-nitro-L arginine methyl ester in combination with indomethacin., Results: Constriction to endothelin-1 was enhanced in idiopathic menorrhagia arteries (P < .05). Idiopathic menorrhagia arteries demonstrated enhanced basal tension after incubation with N(w)-nitro-L arginine methyl ester, which was further exaggerated by indomethacin. NOS inhibition had no effect on basal tension in controls, but basal tension was enhanced after inhibition of cyclooxygenase-derived products (P < .05). Bradykinin-mediated dilation was significantly increased in idiopathic menorrhagia (P < .05)., Conclusion: The presence of functional alterations in small myometrial arteries could contribute to idiopathic menorrhagia.

Objective: The aim of this study was to assess myometrial vascularization with 3-dimensional (3D) power Doppler angiography (PDA) in women with different grades of primary dysmenorrhea at the moment of maximum menstrual pain in an effort to improve the pathophysiologic knowledge of one of the most common gynecologic conditions., Methods: This was a cross-sectional study involving 70 voluntary women that studied or worked at the Clinica Universitaria de Navarra between January 2006 and January 2008. All women underwent transvaginal sonographic 3D PDA on the day of maximum pain after the onset of menstruation or during the first 24 to 48 hours of the new cycle if no pain was present. Three groups were defined according to a visual analog scale: no pain to mild dysmenorrhea, moderate dysmenorrhea, and severe dysmenorrhea. Vascularity assessment was done on the basis of 3D vascularity indices: the vascularization index (VI), flow index (FI), and vascularization-flow index (VFI)., Results: The mean VI and VFI for the inner 5 mm of the myometrium and the total myometrium were significantly higher in the women with severe dysmenorrhea than in those with no pain to mild dysmenorrhea (P < .05). The VI, FI, and VFI in the women with moderate dysmenorrhea did not differ significantly from those in the women with severe dysmenorrhea., Conclusions: This study evaluated the use of 3D PDA for assessing uterine and specifically myometrial vascularization. Our data indicate that women with severe dysmenorrhea have increased myometrial vascularization during the early menstrual phase compared with women without pain.

Microangiography and vascular casting have previously been used to demonstrate the three-dimensional architecture of human uterine microvasculature. However, a limitation of these perfusion-dependent techniques is the difficulty in identifying surrounding tissue components. We have previously shown that it is possible to visualise microvascular networks on the cut surfaces of fresh tissue specimens by diffusive labelling of vascular endothelium with fluorescently conjugated UEA-1 lectin. Unlike perfusion methods that are limited to accessible vascular networks, diffusive fluorescence labelling (DFL) allows additional visualisation of extravascular cellular components, such as smooth muscle. Following UEA-1 DFL, smooth muscle-myosin and -actin were then visualised by immunolocalisation on the acetone-fixed tissue pieces. This allowed clear three-dimensional distinction between the vascular and muscle architecture of the myometrium and endometrium. This method can also be applied for studying the relative distribution of microvascular and muscle architecture in leiomyomas (fibroids). The techniques described in this methodological study provide a simple way of directly examining the uterine vasculature in three dimensions using conventional microscopy, while also distinguishing myometrial from endometrial parts of the network.

Objective: Parathyroid hormone-related protein (PTHrP) has been reported to relax different vessels. We investigated the influence of both endothelium and gestation on the relaxation of uterine arteries (UA), which supply blood to myometrium and placenta., Methods: Small uterine and mesenteric arteries (MA) with (E+) and without endothelium (E-) from day 20 pregnant (P) and nonpregnant (NP) rats were mounted in a myograph, precontracted with phenylephrine (PE) in a physiologic salt solution. Relaxations to PTHrP, acetylcholine, and forskolin were performed and expressed as a percentage of the PE-induced contraction. Blockade of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) was also studied with Nomega-nitro-L-arginine methyl ester (L-NAME) and with charybdotoxin + apamin, respectively., Results: Gestation significantly increases maximal vasodilating effect of acetylcholine in UA (68% vs 52%, P < .05) and sensitivity to acetylcholine in small mesenteric vessels (P < .05). PTHrP relaxes uterine (maximal relaxation P: 32%, NP: 46%), as well as small MA (P: 68%, NP: 89%), but the maximal relaxation is significantly greater in NP than in P rats (P: 32%, NP: 46%, P < .01) in both vascular beds. In addition, in the UA of P rats, PTHrP only produces relaxation if functional endothelium is present; nevertheless in the absence of endothelium, forskolin still elicits relaxation (65%, P < .01). L-NAME significantly impairs relaxation of E+ UA (P < .05), and so does the association of charybdotoxin + apamin (P < .05). Thus, NO and EDHF contribute largely to this vasorelaxant effect., Conclusion: PTHrP induces a relaxation on UA that is strongly endothelium-dependent during gestation, in contrast to what happens simultaneously in MA.

Pre-eclampsia is characterised by a maternal syndrome of hypertension and proteinuria, that is frequently associated with reduced fetal growth. The characteristic histopathological observation in the placental bed is narrowing and atherosis of the distal branches of the uterine arteries at, and around, the deciduo-myometrial interface. In the maternal kidneys there is swelling of the glomerular capillaries and mesangium with some inclusions in the basement membrane ("glomeruloendotheliosis") and evidence of vasoconstriction in many other organs. Untreated maternal hypertension leads to convulsions (eclampsia) which may result in maternal and fetal death. The nerve plexus at the endometrial(decidual)--myometrial interface was first reported in 1959 though has received little attention in the intervening years. It appears to play an important role in maintaining the separation of two tissues with intrinsic proliferative potential (endometrium and myometrium). The present hypothesis proposes that damage to the nerve plexus at the endometrial-myometrial interface causes impaired control of a third proliferative tissue (invading trophoblast) resulting in the characteristic histological changes. Growth factors produced by nerves and blood vessels may contribute to the process of normal placentation e.g. nerve growth factor, vascular endothelial growth factor, etc. and these processes may be compromised in areas of denervation. Neural connections between the uterine and renal innervations (L1, 2) result in renal vasoconstriction and widespread systemic maternal vasoconstriction in an attempt to provide increased blood flow for the uteroplacental circulation (maternal hypertension, small-for-gestational age fetus). Loss of these neural connections through the same process of partial uterine denervation may cause reduced fetal growth without the maternal circulatory changes of pre-eclampsia (maternal normotension, small-for-gestational age, fetus). Variations in maternal circulatory compliance alter the "phenotype" of the condition such that prior maternal hypertension may cause pre-eclampsia through intrarenal mechanisms without significant fetal growth restriction. Increases in circulatory compliance in multiparity prevent the typical features of the condition, or, if they are expressed then they present in a different sequence with haematological and hepatic consequences presenting before the renal manifestations (HELLP syndrome, haemolysis, elevated liver enzymes, low platelets).

Objective: Heavy bleeding in the late postpartum has, in some cases, been attributed to subinvolution of the placental bed and enhanced myometrial vascularity (EMV) as seen on color Doppler imaging. The aim of this study was to investigate the incidence and spontaneous evolution of areas of enhanced vascularization over the whole thickness of the myometrium in asymptomatic women after uncomplicated term pregnancy., Methods: This was a prospective descriptive study involving 93 consecutive women who were examined on day 3 (mean 2.6 +/- 1.5) and at 6 weeks (mean 6.5 +/- 1.3) after delivery following an uncomplicated term pregnancy. EMV was defined as the presence of marked flow over the full thickness of the myometrium reaching the uterine cavity. Doppler flow examination within the area of EMV and of both uterine arteries was performed., Results: The mean patient age was 29.1 years and average parity was 1.7. The mean gestational age at delivery was 39.1 weeks. Areas of EMV were visualized in 50.5% of patients on day 3 vs. 3.9% at 6 weeks. None of the patients required therapy for bleeding problems. The mean pulsatility index and peak systolic velocity in the area of EMV on day 3 were 0.45 +/- 0.30 and 0.37 +/- 0.20 m/s, respectively. A consistent increase in vascular resistance and decrease in blood flow velocity was observed in both uterine arteries between day 3 and week 6., Conclusions: Most areas of EMV reflect intermediate stages in the involution of the placental bed and do not cause abnormal postpartum bleeding. EVM is common in the puerperium, disappears spontaneously in the vast majority of cases, and does not warrant treatment if asymptomatic. Further research is needed to predict the rare cases in which subinvolution of the placental bed leads to heavy bleeding in the late postpartum., (Copyright 2004 ISUOG.)

Objective: The purpose of this study was to evaluate whether a 3-hour incubation with 17beta-estradiol will enhance blood flow- and bradykinin-mediated dilatation and alter pressure-induced basal tone in myometrial resistance arteries from women with preeclampsia and to evaluate the role of nitric oxide in the responses that were observed., Study Design: Blood flow- and bradykinin-mediated dilatation and responses to intraluminal pressure of 60 and 80 mm Hg were compared before and after 3 hours of incubation with 17beta-estradiol (10(-8) mol/L) in isolated myometrial arteries with the pressure myography technique. In separate experiments, the role of nitric oxide on 17beta-estradiol-induced responses was evaluated in the presence of the nitric oxide synthase inhibitor (10(-4) mol/L). Endothelial morphologic condition was evaluated by scanning electron microscopy., Results: Incubation with 17beta-estradiol significantly improved blood flow-mediated dilatation compared with initial blood flow-mediated response in arteries from women with preeclampsia. This effect was nitric oxide mediated, because the nitric oxide synthase inhibitor abolished the response. Arteries from women with preeclampsia demonstrated impaired bradykinin-mediated dilatation compared with that obtained in arteries from normal pregnant women. The 17beta-estradiol had no effect on bradykinin-mediated dilatation in arteries from women with preeclampsia. The enhanced pressure-induced tone at 80 mm Hg compared with the tone that developed at 60 mm Hg in arteries from women with preeclampsia was reduced after incubation with 17beta-estradiol. This reduction was also nitric oxide mediated. Morphologic signs of endothelial dysfunction were evident in arteries from women with preeclampsia., Conclusion: The 17beta-estradiol improved impaired blood flow-mediated dilatation and reduced basal tone through a nitric oxide-mediated pathway in isolated myometrial arteries from women with preeclampsia.

Cryostat sections of arterial and venous vessels from various size branches of the uterine artery and utero-ovarian vein of the pig mesometrium in different phases of the estrous cycle were stained immunohistochemically for endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1) and endothelin B receptor (ETB-R) using ABC method. Immunoreactivity was evaluated according to 6-point scale under light microscope. The differences in immunostaining intensity in the endothelium of the vessels studied at various levels of mesometrium suggest a correlation of eNOS, ET-1 and ETB-R expression with the estrous cycle. In the follicular phase, the highest eNOS immunoreactivity was noticed in arcuate arteries and veins, while immunoreaction of ET-1 was much lower, just as ETB-R. On the other hand, the highest ET-1 immunoreactivity was observed during first 2 days afterovulation, while ETB-R showed low immunoreactivity level during the whole luteal phase. Vessels from the middle part of mesometrium (I degrees and II degrees branches) and large vascular trunks revealed similar staining for eNOS during the cycle as compared to arcuate arteries. Those vessels showed very high immunoreactivity levels for ET-I and ETB-R during first 2 days after ovulation. Our results suggest that during the estrus eNOS, ET-I and ETB-R play a significant role in the regulatory process of blood flow through the mesometrial vessels, that are connected to the uterine horn.

The calcitonin receptor-like receptor (CRLR) can function as a receptor for either calcitonin gene-related peptide (CGRP) or adrenomedullin (AM), depending upon co-expression with members of a novel family of receptor activity-modifying proteins (RAMP). RAMP1 presents the CRLR at the cell surface as a CGRP/AM receptor. RAMP2- and RAMP3-transported CRLR receptors act as AM-specific receptors. However, it is still unknown if this signalling system operates in vivo. Of particular interest is the uterus, where both peptides and their binding sites are known to be present and where both mitogenic and vasodilatory responses to AM and CGRP have been demonstrated. In this study, we examined whether CRLR and RAMP are co-expressed in the same populations of cells in human uterine tissue. Analysis by in-situ hybridization and immunocytochemistry revealed a heterogeneous and cell type-specific distribution of components of this AM/CGRP signalling system. Adrenomedullin mRNA was expressed and evenly distributed across all cell types. CRLR mRNA was predominantly found in blood vessels. RAMP1 expression was specific to myometrial myocytes and vascular smooth muscle cells in uterine arteries. RAMP2 and RAMP3 mRNA were not detectable by in-situ hybridization. The pattern of differential and cell-specific expression of CRLR and RAMP suggests the involvement of CRLR/RAMP1 in the processes of vasodilation, smooth muscle relaxation and angiogenesis in response to AM and CGRP in the human uterus, but also indicates that other receptors may be implicated.

Uterine blood flow (UBF) and uterine artery endothelial nitric oxide synthase (eNOS) expression are greatest during the follicular vs. luteal phase. 17 beta-Estradiol (E(2)beta) increases UBF and elevates eNOS in ovine uterine but not systemic arteries; progesterone (P(4)) effects on E(2)beta changes of eNOS remain unclear. Nonpregnant ovariectomized sheep received either vehicle (n = 10), P(4) (0.9 g Controlled Internal Drug Release vaginal implants; n = 13), E(2)beta (5 microg/kg bolus + 6 microg x kg(-1) x day(-1); n = 10), or P(4) + E(2)beta (n = 12). Reproductive (uterine/mammary) and nonreproductive (omental/renal) artery endothelial proteins were procured on day 10, and eNOS was measured by Western analysis. P(4) and E(2)beta alone and in combination increased (P < 0.05) eNOS expression in uterine artery endothelium (vehicle = 100 +/- 16%, P(4) = 251 +/- 59%, E(2)beta = 566 +/- 147%, P(4) + E(2)beta = 772 +/- 211% of vehicle). Neither omental, renal, nor mammary artery eNOS was altered, demonstrating the local nature of steroid-induced maintenance of uterine arterial eNOS. In the myometrial microvasculature, eNOS was increased slightly (P = 0.06) with E(2)beta and significantly with P(4) + E(2)beta. Systemic NO(x) was increased with P(4) and P(4) + E(2)beta, but not E(2)beta, suggesting differential regulation of eNOS expression and activity, since P(4) increased eNOS in uterine artery endothelium while E(2)beta and the combination further increased eNOS protein.

Light, scanning electron microscopy of endometrial surface and vascular casts were used to study the vascular architecture of the donkey uterus during estrous. The arterial blood supply of the uterus comes from three arteries: the uterine branch of the ovarian artery, the uterine artery of the external iliac artery, and the uterine branch of the urogenital artery. All arteries enter the uterus at its mesometrial border and divide into smaller ones. Segmentally constricted arteries are seen to circumscribe large veins at the perimetrium which become highly convoluted in the intermuscular vascular layer of the myometrium. Small arteries and arterioles originate at the borderline between the myometrium and the endometrium and radiate to the surface of the endometrium to constitute a system of numerous ridges and grooves by a widely meshed plexus of subepithelial capillary network. The post-capillary venules of the endometrium arise from the subepithelial capillary plexus to form slightly larger veins than the concurrent arteries which join up to the large tortuous veins in the intermuscular vascular layer of the uterus. This arrangement of blood vessels in the donkey uterus and particularly in the endometrium provides the requirement for instant blood flow on the arterial side and for the slow flow rate on the venous side to ameliorate the process of substances exchange.

Objective: We sought to compare flow-mediated dilatation and myogenic and norepinephrine-induced tone in myometrial resistance arteries from women with preeclampsia and healthy pregnant women and to evaluate the role that nitric oxide may play in these responses., Study Design: Arteries (approximately 200 microm, at 50 mm Hg) were dissected from myometrial biopsy specimens from women undergoing emergency cesarean delivery because of preeclampsia (n = 6) and from healthy control subjects undergoing planned cesarean delivery (n = 9). Responses to intraluminal flow, pressure, and a constrictor agonist (norepinephrine, 10(-6) mol/L) were studied in the absence and presence of the nitric oxide synthase inhibitor N omeganitro-L -arginine (10(-4) mol/L). Myogenic and norepinephrine-induced tone were calculated after the determination of artery diameter in the absence of extracellular calcium and in the presence of papaverine (10(-4) mol/L)., Results: An increase in intraluminal flow led to dilatation of isolated myometrial arteries from healthy gravid women, whereas flow-mediated dilatation was absent in arteries from gravid patients with preeclampsia (increase in diameter at maximum flow rate of 204 microL/min, 28% +/- 5% in healthy gravid patients vs -15% +/- 6% in gravid women with preeclampsia; analysis of variance, P <.05). Addition of N omega-nitro-L -arginine had no significant effect on flow-mediated responses in arteries from women with preeclampsia, whereas flow-mediated dilatation was abolished after addition of N omega-nitro-L -arginine in arteries from healthy gravid women (increase in diameter at a maximum flow rate of 204 microL/min, 28% +/- 5% control vs -9% +/- 5% N omega-nitro-L -arginine; analysis of variance, P <.05). Arteries from women with preeclampsia developed pressure-induced myogenic and norepinephrine-induced tone, similar to that obtained in arteries from healthy gravid women. In arteries from gravid women with preeclampsia, inhibition of nitric oxide synthase enhanced myogenic-induced tone (25% +/- 4% control vs 35% +/- 5% N omega-nitro-L -arginine; P <.05) and norepinephrine-induced tone (36% +/- 4% control vs 46% +/- 6% N omega-nitro-L -arginine; P <.05), as in arteries from healthy gravid women., Conclusions: Nitric oxide may participate in modulation of pressure- and norepinephrine-induced tone even in preeclampsia, but the shear stress-mediated release of nitric oxide is absent. Failure of shear stress-mediated dilation in myometrial arteries from gravid women with preeclampsia might contribute to the impaired uteroplacental blood flow in this disease.

Menorrhagia is a significant problem in women of reproductive age. In half of the cases no specific aetiology is known. Vascular factors play a role but remain poorly understood. We chose to study whether any association exists between the flow impedance of uterine arteries and the amount of menstrual blood loss. The study population consisted of 60 spontaneously menstruating 35- to 49-year-old women without endometrial hyperplasia, polyps, or submucous fibroids. The pulsatility index (PI) from uterine arteries, arcuate arteries, and radial arteries was measured by transvaginal colour Doppler. Menstrual blood loss was measured by the alkaline haematin method. A significant inverse correlation was found between uterine artery PI and the amount of menstrual blood loss, suggesting that women with lower uterine flow impedance bleed more. A regression model confirmed that this association was specific and not explained by uterine size, fibroids or any other of the 11 potential confounders included in the model. The correlation between uterine artery PI and amount of menstrual blood loss suggests that vascular factors may be involved in the pathogenesis of menorrhagia.

Uterine expression of angiogenic factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [bFGF]) was evaluated in ovariectomized ewes at 0, 2, 4, 8, 24, 48, or 72 h after estradiol (E2) treatment. Endometrial VEGF mRNA increased more than 5-fold from 0 to 4 h, remained elevated at 8 h, and then declined through 72 h after E2 treatment. In contrast, endometrial bFGF mRNA remained constant from 0 to 4 h, increased 2.2-fold from 4 to 8 h, remained elevated at 24 h, and then declined through 72 h. Immunostaining for VEGF was present in myometrial and endometrial microvessels (arterioles, venules, and/or capillaries) and also in myometrial smooth muscle; the pattern of VEGF immunostaining followed that of mRNA expression, being elevated at 4 and 8 h after E2 treatment. Immunostaining for bFGF was present exclusively in uterine glands; the pattern of bFGF immunostaining also followed that of its mRNA, being elevated at 8 and 24 h after E2. On the basis of these observations, we suggest that VEGF and bFGF are probably important factors responsible for the dramatic uterine microvascular response that occurs 8 to 24 h after E2 treatment in ovariectomized ewes.

Objective: This study compared late-pregnant radial uterine arteries that supplied the placenta versus the myoendometrium to evaluate differences in active and passive mechanical properties., Study Design: Pressurized segments of placental versus myoendometrial radial uterine arteries from late-pregnant (day 28 to 30) New Zealand White rabbits (n = 12) were compared in vitro for differences in luminal diameter, wall thickness, distensibility, and intrinsic tone as a function of transmural pressure., Results: Both types of arteries responded to increased transmural pressure with active vasoconstriction; however, the amount of tone present in myoendometrial arteries was significantly greater than in placental arteries (percent tone at 75 mm Hg = 39% +/- 3% for myoendometrial versus 31% +/- 2% for placental arteries, p < 0.01). Measurements of unpressurized, fully relaxed arteries revealed that placental arteries were 38% larger in diameter and had thicker walls than myoendometrial arteries did. However, myoendometrial arteries were significantly more distensible at transmural pressures >5 mm Hg., Conclusions: The increased size and diminished tone of placental compared with adjacent myoendometrial arteries would favor increased blood flow to the placenta; differences in size and passive mechanical properties suggest that a localized factor(s) originating from the fetus or placenta contributes to the gestational enlargement of those arteries that perfuse the placenta.

In mated sows, the level of placental vascularization has a direct effect on fetal growth and litter birth weight. Vascularization of the endometrium and uterus under the control of various polypeptide growth factors is an important early stage in this process. Basic fibroblast growth factor (FGF-2), a polypeptide distributed throughout the mesodermal and neuroectodermal tissues of many species, is a vascular endothelial cell mitogen in vitro and has been implicated in neovascularization and wound healing in vivo. As part of our studies of the distribution of FGF-2 in uterine tissue and its role in placental development and embryo implantation, the localization and changes in the abundance of porcine FGF-2 mRNA in the uterus of mated and unmated gilts were investigated by in situ hybridization procedures. These procedures were based on the use of [alpha35S]-dATP-labeled oligonucleotide probes and a novel set of digoxigenin-labeled oligonucleotide probes generated by reverse transcriptase-polymerase chain reaction (RT-PCR) methods and anti-sense labeling strategies from the corresponding mRNA templates. With these in situ hybridization procedures, porcine FGF-2 mRNA was localized during the first 30 days of pregnancy to specific tissue areas in the porcine uterus comprising glandular and luminal epithelial cells and stromal cells of both the stratum functionalis and stratum basalis regions of the endometrium, and within the smooth muscle of myometrium and the associated blood vessels. However, no significant increase in the level of FGF-2 mRNA within these tissues was detected during these early stages of pregnancy or during the estrous cycle of unmated gilts. These distribution and abundance patterns are only partially compatible with other recent observations suggesting a possible role for changing levels of the mature polypeptide form of FGF-2 in the reproductive tract of sows during the early stages of pregnancy.

The H2 gas clearance technique was employed to measure uterine blood flow (UBF) in ovariectomized rats. A needle-type platinum electrode (125 microns diam) was inserted into the rat uterine wall to measure the tissue blood flow surrounding the electrode. The electrode can be placed in individual layers of the uterus to measure the endometrial blood flow (EBF) or the myometrial blood flow (MBF). By use of this technique, baseline EBF and MBF were 37.8 +/- 3.53 (n = 21) and 47.2 +/- 4.56 (n = 5) ml.min-1.100 g-1, respectively, with an EBF/MBF ratio of 0.8. Intravenous bolus injection of 17 beta-estradiol (1 microgram/kg) induced a significant increase in UBF. Phenylephrine, an alpha-adrenergic receptor agonist, reduced UBF. In some animals, a second platinum electrode was used to measure gastric mucosal blood flow simultaneously with UBF. While 17 beta-estradiol selectively increased UBF, pentagastrin selectively increased gastric mucosal blood flow. To further validate the baseline UBF distribution between endometrial and myometrial layers, iodo[14C]antipyrine autoradiography was employed. With the iodo[14C]antipyrine technique, the EBF/MBF ratio was 0.91 +/- 0.07 (n = 5), which is similar to that obtained with the H2 gas clearance technique.

Activities of total monoamine oxidase (MAO-T) and of both subtypes: MAO-A and MAO-B were examined in the uterine artery, vessels of ovarian pedicle (subovarian veno-arterial network), mesenteric artery and myometrium on the 0-2nd, 13-14th and 16-18th days of the oestrous cycle of pigs. It was found that in the uterine artery MAO-T, MAO-A and MAO-B activities were the highest on the 0-2nd days (100%); on day 13-14 they were lower by 85.4, 84.8 and 87.4% (p < 0.01), respectively, and on days 16-18 they were lower by 52.4, 57.5 and by 54.1% (p < 0.01) in comparison with the value on the 0-2nd days of ovarian cycle. The activities of MAO-T, MAO-A and MAO-B in the vessels of ovarian pedicle on the 0-2nd days were the lowest, whereas on days 13-14 they were the highest (p < 0.01), MAO-T by 445.3%, MAO-A by 315.6%, MAO-B by 344.7%, and they were higher on days 16-18 by 133.8% (p < 0.01), 85.9 (p < 0.05) and by 281.5% (p < 0.01) in comparison with the value on the 0-2nd day of ovarian cycle, respectively. The activities of examined enzymes in mesenteric artery were higher on 0-2nd and 16-18th days, whereas MAO-T and MAO-B they were lower by 39.0% and MAO-A by 22.3% (p < 0.05) on 13-14th days of oestrous cycle. In myometrium the activities of MAO-T, MAO-A and MAO-B on the 0-2nd days (100%) were the lowest, whereas on days 13-14 the activities were the highest (p < 0.01), MAO-T by 326.3%, MAO-A by 363.3% and MAO-B by 364.1%, and on days 16-18 the MAO-T and MAO-B activities were also higher by 99.4% and 150.7% (p < 0.01) respectively, whereas MAO-A activity was similar to the value on the 0-2nd days. The high MAO activity in the vessels of pig ovarian pedicle may be a significant factor in the ovarian vasotone decrease and increase in the ovarian blood flow during the luteal phase of ovarian cycle.

Expression of vascular cell adhesion molecule (VCAM) and endothelial leukocyte adhesion molecule (ELAM)-1 on human uterine endothelium was examined by immunohistochemistry. Endomyometrial blocks were obtained from 26 hysterectomy specimens (n = 6, menstrual; n = 6, follicular; n = 14, luteal). VCAM and ELAM-1 expression was compared to that of the classic endothelial markers Factor VIIIRA, CD31, CD34 and CD36, which were found to be present in samples taken from all stages of the cycle. Factor VIIIRA, CD31 and CD34 were expressed on most endothelium whereas CD36 was expressed primarily on that of small vessels. CD36 was also found to be strongly expressed on endometrial epithelium and no changes were apparent during the menstrual cycle. ELAM-1 expression was not detected in any of the tissues examined. VCAM expression varied during the cycle, appearing on endometrial endothelium in the mid- and late luteal phases, stages at which large granular lymphocytes migrate into endometrium. VCAM or a VCAM-like molecule may be involved in migration of large granular lymphocytes into endometrium.

The mechanisms that mediate changes in uterine activity from a quiescent state during pregnancy to active labor at parturition are unknown. Nitric oxide (NO), a potent mediator of smooth muscle relaxation, and its presence in the uterus is the subject of this report. Nitric oxide synthase (NOS) activity was demonstrated in nerves, blood vessels and decidua of gravid rat uterus by the NADPH-diaphorase staining method. Uterine tissue fixed during labor demonstrated markedly less NOS. Quantitation of NOS activity in subcellular fractions of pregnant and laboring uterus revealed its presence in both the cytosolic and the membranous compartments of uterine homogenates. In both cellular subfractions the enzyme activity decreased significantly from pregnancy to term. We conclude NOS is present in multiple structures within the uterus. Its presence in two cellular compartments suggests more than one form of NOS may be present in the uterus. Reduction in NOS activity at parturition suggests NO may contribute to the maintenance of uterine contractile quiescence during gestation.

The haemodynamics of the uterine arteries and myometrium were assessed using Doppler ultrasound in forty consecutive patients requiring treatment for invasive mole and choriocarcinoma. The investigations were performed prior to the commencement of chemotherapy and the subjects followed prospectively. The Doppler waveforms from the uterine arteries were analysed using the pulsatility index. It was found that patients with a pulsatility index of 1.1 or less were significantly more likely to develop drug resistance than those with a higher value (P < 0.04). There was no significant association between the pulsatility index and metastatic disease or uterine bleeding. Five out of eight patients who developed drug resistance could have avoided initial inadequate treatment if the Doppler findings were included in the scoring system for selecting chemotherapy for these tumours. It can be concluded that assessment of the uterine arteries using the pulsatility index prior to the treatment of patients with invasive mole and choriocarcinoma is of help in predicting those who will develop drug resistance.

The postnatal development of noradrenaline (NA)-containing nerves of the rat uterus and its associated blood vessels was investigated using histochemical and biochemical methods. These studies were carried out in conjunction with examination of the morphology of the uterus and the density of blood vessels at the prepubertal, peripubertal and adult stages. It was demonstrated that: (1) the rat uterus is innervated at birth; (2) the innervation of blood vessels develops earlier than that of the myometrium and the density of NA-containing perivascular nerves is not affected by puberty; (3) between birth and day 30 (prepubertal) there was a progressive increase in the innervation of the myometrium which was accompanied by a progressive increase in the total NA content of the organ; (4) at the first oestrus there was a marked increase in the weight of the uterus and isolated myometrial and parametrial tissue. Both muscle cell size and number were also increased. The density of myometrial innervation by NA-containing nerves was markedly reduced, although the total NA content did not change at this stage. This indicates a 'dilution' of myometrial NA-containing nerves in a greater amount of non-neuronal tissue; and (5) between the peripubertal and adult stages there was a further increase in uterine weight together with an increase in the number of smooth muscle cells and a reduction in the density of myometrial NA-containing nerves. Although the density of perivascular nerves was unaffected by puberty, the number of blood vessels supplying the uterus increased during the transition to the adult stage. This was reflected by a significant increase in the total NA content of the uterine horn and of isolated myometrial and parametrial preparations.

We investigated the effects of synthetic human relaxin (hRLX-2) on isolated rat and human myometrium and on uteroplacental arteries from term pregnant women. The preparations were mounted in organ baths and isometric tension was recorded. In isolated myometrium from nonpregnant rats, hRLX-2 (10(-10)-10(-7) mol/L) produced concentration-dependent inhibition of contractile activity induced by vasopressin (10(-8) mol/L). In isolated human myometrium from the fundus or isthmus, hRLX-2 (10(-10)-10(-7) mol/L) did not influence spontaneous activity or contractions induced by oxytocin (10(-9) mol/L) and prostaglandin (PG) F2 alpha (10(-5) mol/L). Nor did it influence the tension induced in small intramyometrial arteries by U46619 (10(-7) mol/L), noradrenaline (10(-5) mol/L), and endothelin (10(-9) mol/L); or the tension induced in fetal stem villus arteries by U46619 (10(-7) mol/L), endothelin (10(-9) mol/L), and PGF2 alpha (10(-5) mol/L). The inhibitory effects of hRLX-2 in preparations of rat myometrium were not influenced by the presence of human myometrium in the organ bath or by pre-incubation of hRLX-2 with human myometrium. These results suggest that direct inhibitory effects of relaxin may be of minor importance for the regulation of myometrial activity and uteroplacental circulation in term human pregnancy.

Structure of the blood bed has been studied in normal rat uterus and at ageing. Phenomena of involutive changes in the blood bed have been demonstrated. They depend on the process of sclerosis in the organ and desolation of vessels.

In pregnant Syrian hamsters (Mesocricetus auratus) used as an animal model for studying the migration of fetal trophoblasts and the associated changes in maternal blood vessels, intravascular trophoblasts migrated well beyond the blood vessels of the uterus and into the vessels of the mesometrium. They migrated beyond the decidua of the uterus, into the lumina of maternal uterine and mesometrial arteries, but not into veins. The arterial changes, which were often segmental, resembled those seen in the decidua and consisted of a replacement of normal smooth muscle cells by poorly differentiated stromal cells. Ultrastructurally, the trophoblasts were either above or below maternal endothelial cells. They occurred also as single or multiple layers within the lumina of arteries that lacked an endothelial lining. Apparent penetration of the elastic membrane by the fetal trophoblasts brought them into close apposition to maternal cells in the arterial wall. Histochemical studies showed heightened metabolic activity of the intravascular trophoblasts as suggested by strong histochemical reactions to nonspecific esterase, succinic dehydrogenase and the glycerophosphate dehydrogenase reactions. Thus, these metabolically active fetal trophoblasts actively migrate into the maternal arterial system, resulting in loss of endothelial cells and changes in the wall of the maternal arteries similar to those in the decidua at the uteroplacental junction.

Arteriovenous malformation of the uterus is rare. It is potentially lethal because profuse, uncontrollable bleeding may occur with diagnostic dilatation and curettage. Several cases of localized uterine arteriovenous malformation have been reported on. The condition should be considered during routine vaginal examination with pulsation and thrill in the vaginal fornices, even if there is a normal menstrual history, as in our patient. In our patient, pathologic examination of the uterus demonstrated for the first time an extensive, diffuse, tortuous arteriovenous anastomosis extending from the upper uterine segment down to the stroma of the exocervix. In such cases a thorough clinical and (if indicated) radiologic evaluation should be done before curettage, or even cone biopsy, to avoid possible massive hemorrhage.

An experimental study on pregnant rats was undertaken to explore whether renal hypertension interferes with uteroplacental blood supply and fetal weight. Renal hypertension was induced by standardized clamping of the left renal artery. Two days before expected delivery, blood flow to the reproductive organs was determined by microsphere technique in normal control rats, rats with short-standing renal hypertension induced early in pregnancy, and rats with established renal hypertension induced 4 weeks before pregnancy. Myometrial and placental blood supply was considerably reduced in renal hypertensive rats compared to that in normotensive pregnant rats, with the reduction in placental blood flow being as much as 68% in rats with established renal hypertension. Nevertheless, there was no reduction in fetal weights, placental weights, or number of fetuses in the litters. These findings suggest that the nutritional blood supply of the placenta normally has a considerable overcapacity, perhaps a necessary safety margin so that the fetus can manage the circulatory demands associated with delivery. If hypertension causes intrauterine growth retardation only by means of reduced placental blood flow, this reduction in flow obviously must be considerable.

In vivo experiments were performed on the uterine tissue of non-pregnant estradiol treated rabbit anesthetized with sodium pentobarbitone. The average blood flow calculated from the washout of Xenon-133 after atraumatic labelling from the uterine surface was 25.4 ml . min-1.(100 g)-1 (range 7.4-66.6), and after local injection of a tracer in isotonic saline directly into the myometrium 24.4 ml.min-1.(100 g)-1(range 8.7-45.3). During the experiments a monoexponential washout curve was found for the whole washout process both after atraumatic labelling and when the injected volume was 5 microliter. No trauma of injection was observed using this injection volume. The results support the applicability of a monocompartmental model for the washout of inert gas from the myometrium. Thus myometrial blood flow can be calculated from the Xenon-133 washout rate at any time interval during the washout process.

Morphometric and statistical techniques were used to assess the relation of myometrial interstitial trophoblast to the uteroplacental vasculature in 27 intact hysterectomy specimens ranging from 8 to 18 weeks' gestation. It was found that the volume density of cytotrophoblast in the myometrium and in particular the proximity of such trophoblast to the placental bed spiral arteries correlated significantly with morphological alterations in these vessels. The changes included swelling of endothelium, hypertrophy of individual medial smooth muscle cells, and oedema and disruption of the architecture of the vessel wall as a time-related continuum. Some of the changes, such as swollen endothelium and basophilia of medial smooth muscle cells were noted also in spiral arteries in the non-placental bed endometrium but to a considerably less extent than in the placental bed. Intimal vacuolation was common to placental bed and non-placental bed arteries, increased with gestational age and can be considered as a non-specific feature. The migration of endovascular trophoblast into the myometrial spiral arteries in the second trimester occurred only when these arteries had been considerably altered in their morphology. These findings indicate that migratory interstitial cytotrophoblast probably has a role to play in the preparation of the myometrial segments of the uteroplacental arteries for the second wave of endovascular trophoblast migration that occurs in the second trimester of human pregnancy.

The presence of vasoactive intestinal polypeptide (VIP), substance P (SP), somatostatin, enkephalin, and avian pancreatic polypeptide (APP) in nerves in the female genital tract raises the question of their physiological significance as neurotransmitter substances. We have examined the effect of these peptides on non-vascular uterine smooth muscle in vivo as well as in vitro, and the effect on blood flow in the genital tract of rabbit and cat. SP caused a dose-dependent increase in mechanical and myoelectrical activity, an action which could be antagonized by VIP. Substance P, leu-enkephalin and VIP induced a concentration related increase in blood flow of the uterus, where VIP seems to be the most potent vasodilator. Neither the effects on vascular nor on non-vascular smooth muscle were inhibited by adrenergic nor cholinergic blocking agents. APP was able to inhibit the VIP-induced vasodilation in rabbits. These findings suggest that several peptides are involved in the local nervous control of both uterine contractions and haemodynamic events.

The authors measure the changes in placental and myometrial blood flow using an isotope technique with Indium 113. They calculate an index of the variation in placental blood flow (I.V. D.P.) and an index of variation of myomoetfrial blood flow (I.V.D.M.) after injecting Ritodrine or a placebo between the 28th and the 36th week of pregnancy. This study was carried out in 26 normal women. At the same time using Brotanek's technique changes in the cervical blood flow were registered. No change in the placental, myometrial or cervical blood flows were noted while Ritodrine was being transfused intravenously.

The use of beta-adrenergic agonists in high-risk pregnancies has shown evidence of favorable effects on the fetus. Intravenous injections of 133Xe were given to evaluate the effects of short-term administration of fenoterol (3 microgram/min) and isoxsuprine (150 migrogram/min) on the intervillous and myometrial blood flow in a series of 48 women during the last trimester of pregnancy. Both fenoterol and isoxsuprine treatment increased the maternal heart rate significantly. There was a significant rise in myometrial blood flow when fenoterol was given, but the intervillous blood flow did not change significantly during the administration of either isoxsuprine or fenoterol. Previous oral isoxsuprine treatment did not diminish the cardiac effect of intravenous fenoterol, but the improvement in myometrial blood flow was eliminated. This result indicates that beta-adrenergic agonists may have a specific dilatational effect on the myometrial blood vessels. From the hemodynamic point of view, the beta-adrenergic agonists have a limited value in the treatment of chronic fetal asphyxia or intrauterine fetal growth retardation.

The distribution and effects of the two neuropeptides, vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine amide (PHI), on vascular and nonvascular smooth muscle in the urogenital tract of nonpregnant rabbit female, were investigated. Immunoreactive VIP and PHI were present in all regions except the ovary with the highest concentration in the uterine cervix. By using in vitro tension recordings of myometrial specimens, it was demonstrated that both peptides displayed a dose-dependent inhibition of the mechanical activity. The dose-response curves of VIP and PHI were superimposable with and ID50 of 3 X 10(-8) mol/l, and their combined effect was additive. In addition, the influence of the two peptides on myometrial blood flow (MBF) was investigated by the xenon-133 washout technique. Both peptides were found to increase MBF with the same potency and efficacy. Their combined effect was additive. In conclusion VIP and PHI are present in the rabbit urogenital tract, and the two peptides are equipotent inhibitors of mechanical nonvascular and vascular smooth muscle activity in the uterus.

The rates and distributions of uterine blood flow (UBF) were measured in conscious castrated ewes during estradiol, progesterone, and combined-hormone regimens. Supplemental progesterone decreased the magnitude of UBF observed on estradiol alone. Progesterone favored distribution of UBF to the uterine caruncles and estradiol favored distribution to the myometrium and uterine cervix. Proportionate endometrial blood flows were similar on all hormone regimens. These observations suggest that estradiol secretion may not be responsible for the definitive increase in UBF observed during ovine pregnancy.