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This study assesses the ability of plasma from women with pre-eclampsia to induce altered endothelial function in myometrial resistance vessels from normotensive women. Vessels from normotensive pregnant women (n = 7) were incubated with plasma from other pregnant women who were normotensive (n = 6) or had pre-eclampsia (n = 7). A wire myograph was used to test the endothelium-dependent relaxatory response to bradykinin of preconstricted vessels. The relaxation in vessels incubated with plasma from women with pre-eclampsia was markedly less than in vessels incubated with plasma from normotensive pregnant women (P = 0.039). This supports the theory that a plasma-borne factor contributes to the endothelial changes seen in pre-eclampsia.

Objective: To measure endothelium-dependent relaxation in myometrial resistance arteries and to compare this parameter in nonpregnant and normotensive pregnant women and those with pregnancies complicated by pre-eclampsia., Design: A prospective study., Setting: Nottingham City Hospital., Sample: Thirty-seven nonpregnant women undergoing hysterectomy and 51 pregnant women undergoing caesarean section, of whom there were 39 normotensive and 12 with pre-eclampsia., Methods: Resistance arteries, dissected from myometrial biopsies, were mounted on a wire myograph and preconstricted with vasopressin then subjected to incremental doses of bradykinin., Results: Endothelium-dependent relaxation to bradykinin was seen in the vessels of nonpregnant and normotensive pregnant women. Markedly reduced endothelium-dependent relaxation was found in the myometrial arteries from women with pre-eclampsia when compared with both nonpregnant (P < 0.0001) and normotensive pregnant (P < 0.0001) women., Conclusion: A significant loss of endothelium-dependent relaxation in myometrial resistance arteries in pre-eclampsia may contribute to the altered vasoreactivity seen in pre-eclampsia, and particularly to the decreased placental perfusion and fetal growth retardation commonly associated with this condition.

The 133Xe washout method has been evaluated and found to be a reliable method for the measurement of myometrial as well as ovarian blood flow rates in the rabbit. Monoexponential washout curves for 133Xe have been demonstrated for the whole washout process, both in the uterus and the ovary. Consequently it is possible to calculate the blood flow rate at any time interval during the whole washout process. This 133Xe washout technique has been used for the evaluation of the biological effect of neuropeptides on the local blood flow within the rabbit uterus and ovary. It has been recognized for years that the intrinsic control of a number of functions, including the blood flow regulation, in the genital tract cannot be attributed to cholinergic and/or adrenergic nerves alone. Evidence from 133Xe experiments suggests that the neuropeptides in the female genital tract may play a functional role in these non cholinergic non adrenergic events.

The effects of Mg2+ were studied in human umbilical arteries, stem villous arteries and maternal intramyometrial arteries. The vessels were dissected and mounted in organ baths, and isometric tension was recorded. In all fetal preparations investigated, Mg2+ (0.5-6.0 mM) in a concentration-related way decreased pD2 values for prostaglandin F2 alpha responses. The maximum response to prostaglandin F2 alpha was depressed in umbilical arteries, but remained unaffected in stem villous artery preparations. In stem villous arteries pretreated in Ca2(+)-free medium, increasing concentrations of Mg2+ markedly depressed the response to Ca2+ after stimulation with K+ or prostaglandin F2 alpha, suggesting that Mg2+ inhibited transmembrane calcium influx and interfered with intracellular calcium effects. In both stem villous and intramyometrial arteries, increasing concentrations of Mg2+ increased EC50 values for responses to K+, whereas Emax values were unaffected. Mg2+ produced relaxation of agonist-induced contractions by up to 60% in stem villous arteries and up to 40% in intramyometrial artery preparations. The relaxant effect of Mg2+ did not seem to be mediated through the endothelium or through changes in the synthesis of prostanoids, since endothelial disruption and treatment with indomethacin left the responses to Mg2+ unaffected. Relaxation of vessels important for resistance regulation in the human uteroplacental vascular bed may be of benefit when uteroplacental blood flow is impaired, and the present results support the established use of magnesium sulphate in the treatment of pre-eclampsia.

The uterine circulation in 38 patients with invasive mole or choriocarcinoma were investigated using Doppler ultrasound. Twenty-six non-pregnant and 23 pregnant volunteers were assessed in a similar fashion to act as control groups. The pulsatility indices were significantly lower in the patients with trophoblastic disease when compared with the non-pregnant and pregnant groups (Student's t-test; P less than 0.001 and P less than 0.02 respectively). The uterine circulation in persistent trophoblastic diseases shows a characteristic Doppler profile suggesting the presence of large low resistance blood vessels. This may be useful in the initial assessment of these tumours before cytotoxic chemotherapy.

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.

Vasoactive intestinal polypeptide (VIP) containing nerve fibres have previously been demonstrated in the female genital tract of several mammalian species including the rabbit. These nerve fibres seemingly innervate vascular and non-vascular smooth muscle. For that reason we investigated the dose-relationship between VIP (5, 50, 500 pmol . min-1 . kg-1) and myometrial blood flow (MBF) using Xenon-133 washout technique. VIP increased MBF dose-dependently. VIP was on molar base 100 times more potent than acetylcholine. The action of VIP seems to be direct on vascular smooth muscle rather than mediated by other neurotransmitters, because the MBF increase was not antagonized by atropine, adrenergic blocking agents or naloxone. These findings make it likely that VIP plays a role in the local nervous control of myometrial blood flow.

Endometrium and myometrium were collected at hysterectomy from 42 women with measured menstrual blood loss (range 4-840 ml). The specimens, obtained throughout the menstrual cycle, showed no evidence of organic disease on histological examination. The volume fraction occupied by arteries at the myometrial-endometrial junction, and by glandular tissue throughout the endometrium was estimated with a point counting technique. The index of volume-to-surface ratio of endometrial glandular tissue was examined by a combination of point counting and linear intercept methods. No correlation was found between menstrual blood loss and endometrial and myometrial arterial density, endometrial glandular density and volume-to-surface ratio. Consequently, menorrhagia, occurring in the absence of obvious pathology, does not appear to result from an excessive number of arteries of from abnormal glandular distribution.

Small intramyometrial arteries and pieces of adjacent myometrial tissue were obtained from 25 non-pregnant women undergoing hysterectomy. Vascular and myometrial preparations were dissected, mounted in organ baths and isometric tension was recorded. Myometrial strips, but no vascular preparation, developed spontaneous contractile activity. Noradrenaline (NA) and vasopressin (VP) contracted both vessels and myometrium. Prostaglandin F2 alpha (PGF 2 alpha) contracted the myometrial tissue, but had only a minor effect on the vessels. Removal of extracellular calcium almost abolished the myometrial responses to high K+ (124 mM)-solution, PGF 2 alpha, NA and VP. The vascular responses remaining after this treatment were 18% (K+), 34% (NA) and 25% (VP) of control contractions induced by high K+ (124 mM). Nifedipine potently depressed myometrial contractions induced by NA and VP, but was less active against the vascular responses to these agents. In preparations exposed to calcium-free medium, nifedipine (10(-7) M) almost abolished myometrial contractions induced by calcium in the presence of K+ (124 mM), NA or VP. It also effectively depressed vascular responses to calcium in the presence of K+, but was less active if NA and VP were present. It is suggested that PGF2 alpha has almost no contractant effect on intramyometrial arteries, and that the activation process in these vessels is much less dependent on extracellular calcium than that of the myometrium.

A new 'non-invasive' method for measuring intervillous and myometrial blood flow is presented. After 2 mCi of 133Xe in physiological saline was injected intravenously the patient held her breath for 20 seconds. The tracer entered the placenta as a short bolus and its removal was followed with a scintillation detector. Intervillous and myometrial blood flow per unit volume was calculated from the two-exponential curve. The mean +/-SD intervillous flow in normal pregnancy was 135+/-49 ml/minute/100 ml, the corresponding half time being 0-56+/-0-16 minutes. The myometrial flow was 7-7+/-2-5 ml/minute/100 g. The method gave reproducible results and took only 20 minutes to perform. The dose of radiation to the mother was less than 1 mrad.

Placental bed biopsies were obtained at caesarean section from 34 women. Their plasma urate was directly related to maximum mean arterial pressure and inversely to adjusted birthweight; but it was related most closely to the histological appearances of the spiral arteries in the placental bed. Nine women had physiological changes in the spiral arteries: their mean urate (233, SD 28.9 mumol/l) was significantly (P less than 0.001) lower than the mean urate in those who did not have adequate physiological changes (339, SD 90.3 mumol/l) or that in the nine women who had atherosis (397, SD 153.2 mumol/l). Raised plasma urate appears to be better related to maternal vascular pathology than to the clinical condition or infant birthweight.

Uteroplacental spiral arteries in placental bed biopsies and placentas form 80 pregnancies were studied by light and electron microscopy; of these 30 were complicated by fatal growth retardation(less than 10th centile) and 45 by hypertension during pregnancy. The physiological changes of the spiral arteries and the vascular pathology present in hypertensive pregnancy and fetal growth retardation were investigated. In normotensive pregnancies complicated by fetal growth retardation, the physiological changes of pregnancy frequently did not extend beyond the decidual segments of the utero-placental arteries. In pregnancies complicated by pre-eclampsia, the physiological changes of pregnancy were not always restricted to the decidual segments of the utero-placental arteries. Atheromatous-like lesions of similar morphology were found in spiral arteries from both normotensive and hypertensive pregnancies complicated by fetal growth retardation. No arteriopathy was found which was specific for pre-eclampsia.

Tissue specimens from various parts of the uteroplacental unit were obtained from women undergoing caesarean section, and placental tissue from women with normal deliveries. Strips of myometrial tissue, and segments of intramyometrial arteries were dissected together with segments of chorionic plate arteries and veins, and stem villous arteries. The preparations were mounted in organ baths, isometric tension recorded, and the responses to angiotensin II, vasopressin, and oxytocin were studied. In myometrial preparations, angiotensin caused a slight, transient increase in the frequency of spontaneous contractions, but no changes in amplitude. In all vascular preparations angiotensin produced concentration-related contractions. The responsiveness of the preparations was myometrial artery greater than villous artery greater than chorionic plate artery = chorionic plate vein. All responses were transient and tachyphylaxis was pronounced in all tissues. Tachyphylaxis was not influenced by pretreatment with indomethacin. Vasopressin increased transiently frequency and amplitude of contractions in myometrial strips. Myometrial arteries responded with a sustained contraction, as did chorionic plate arteries and veins but the latter vessels were less responsive. Villous arteries did not respond to vasopressin. Oxytocin preferentially stimulated myometrial strips, but also had a weak concentration-related contractant effect on chorionic plate arteries and veins. Villous arteries did not respond to oxytocin. At a higher concentration, causing a pronounced increase in the frequency and amplitude of contractions of myometrial strips, oxytocin abruptly caused a marked contraction of myometrial arteries. Lower concentrations of the peptide had almost no effects. The results suggest that various smooth muscle tissues of the human uterus and placenta are highly differentiated as regards responses to angiotensin II, vasopressin, and oxytocin. The physiological and possible clinical importance of the present findings deserve further investigation.

Tissue specimens of human myometrium and placenta were obtained at caesarean section and normal vaginal deliveries. Strips of myometrial tissue, and segments of intramyometrial arteries, chorionic plate arteries and veins, and stem villous arteries were dissected. The preparations were mounted in organ baths, and isometric tension was recorded. In myometrial preparations, prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), noradrenaline (NA) and serotonin (5-HT) all caused concentration-related contractions. In vascular preparations, the maximum contractant or relaxant effect, Emax or Imax, and the drug concentrations causing half maximum responses, EC50 or IC50 were determined. In intramyometrial arteries no significant differences between Emax or EC50 values were found for NA, 5-HT and PGF2 alpha. The Imax values (relaxation of vessels contracted by vasopressin) ranged prostacyclin (PGI2) greater than PGF2 alpha = PGE2, and the IC50 values PGF2 alpha = PGE2 = PGI2 (PGF2 alpha less than PGI2). Thus, PGF2 alpha showed dual effects. Only PGI2 relaxed placental vessels contracted by PGF2 alpha. In chorionic arteries, Emax values ranged PGE2 = PGF2 alpha greater than 5-HT greater than NA, and IC50 values 5-HT less than NA = PGF2 alpha = PGE2. In stem villous arteries, Emax ranged PGE2 = PGF2 alpha greater than 5-HT = NA, and EC50 5-HT = NA = PGE2 = PGF2 alpha. In chorionic veins the order of Emax values was PGF2 alpha = PGE2 greater than 5-HT greater than NA, and that of the EC50 values 5-HT less than NA = PGF2 alpha = PGE2. Smooth muscle tissues from the human uteroplacental unit show individual responses to prostanoids and amines, probably reflecting individual mechanisms for control of contractile activity and blood flow.