Activity changes of vasoactive autacoids during passage through the human fetoplacental vasculature.
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Angiotensin II↗
Biomedical subjects
W A Walters
Publications and source records attributed to W A Walters.
Characterization of thromboxane A2 receptors in the human fetal placental vessels and umbilical vein.
An in vitro examination has been made of the thromboxane A2 receptors in human fetal placental villous vessels and umbilical veins utilizing the TxA2 agonist U46619 and its competitive antagonist AH22921. U46619 was a potent constrictor of both preparations. The EC50 were 25.3 nmol/l (s.e.m. = 2.5, n = 8) for causing constriction of perfused villous vessels and 22 nmol/l (s.e.m. = 5, n = 17) for contraction of the venous longitudinal strip. AH22921 competitively antagonized responses to U46619 in both preparations. The pA2 values were not significantly different and their 95% confidence limits, obtained for its ability to antagonize responses to U46619 in villous vessels and the umbilical vein, were 8.0 (7.3-8.8) and 7.1 (6.3-7.9) respectively. It is concluded that TxA2 receptors in both the human fetal placental villous vessels and umbilical vein may be similar. They also may be similar to those in human platelets and pulmonary blood vessels.
Biphenyl Compounds↗
Attenuation of pressor responses to sympathetic stimuli in the rat by enalapril.
Intravenous administration to pithed Wistar rats of the angiotensin converting enzyme inhibitor enalapril (0.1-1.0 mg/kg) lowered the diastolic blood pressure and reduced pressor responses occurring during electrical stimulation (1-30 Hz) of the spinal sympathetic outflow. These doses of enalapril given intravenously also attenuated pressor responses to intravenous injection of the muscarinic ganglion stimulant McNeil-A-343 (50, 100, 150 micrograms/kg) and noradrenaline (0.1-5.0 micrograms/kg). Enalapril (1.0 mg/kg, i.v.) reduced pressor responses to the nicotinic ganglion stimulant 1,1-dimethyl-4-phenyl-piperazinium (300 micrograms/kg, i.v.). These results confirmed that the actions of enalapril resemble those of captopril in the pithed rat, by causing reductions in both blood pressure and pressor responses to sympathetic stimuli.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
Haemodynamic changes and left ventricular performance during high-dose oestrogen administration to male transsexuals.
Serial haemodynamic and systolic time interval measurements in 17 male transsexuals during high-dose oestrogen administration were compared with control values obtained after oestrogen withdrawal. During oestrogen treatment, cardiac output, stroke volume, plasma volume and total blood volume increased while total peripheral resistance, diastolic blood pressure and red cell mass decreased significantly. Changes in heart rate and systolic blood pressure were not significant. Despite a much higher dose of oestrogen, the haemodynamic changes observed in this study are similar in magnitude to those occurring in women taking oral contraceptives. Significant changes in systolic time intervals during oestrogen treatment were a shortened pre-ejection period (PEP) index, a prolonged left ventricular ejection time (LVET) index and a decreased PEP/LVET ratio indicating that left ventricular performance was augmented.
Adult↗
Acetylcholine output and foetal vascular resistance of human perfused placental cotyleda.
The foetal villous vessels of single cotyleda of human placentae have been perfused with a constant flow of Krebs solution, recording inflow pressure and passing the venous perfusate in cascade over guinea-pig ileum and rat stomach strip preparations in vitro. Each cotyledon released for at least 4 h a substance that was probably acetylcholine. The perfusate caused contractions of both preparations which were inhibited by atropine or hyoscine and potentiated by physostigmine. Contractile activity was destroyed after incubation at 37 degrees C of perfusate with acetylcholinesterase but not with acetylcholinesterase plus physostigmine. When the perfusion temperature was lowered to 34 degrees C or below, acetylcholine output was reduced, the extent depending on the fall in temperature. No change in resistance of the villous vessels occurred during the changes in temperature or in the presence at 37 degrees C of atropine, hyoscine, hexamethonium, (+)-tubocurarine, hemicholinium-3 or bretylium. Submaximal vasoconstrictor responses of the villous vessels to the thromboxane A2-mimetic U46619 were not affected by reduction of the perfusion temperature to 30 degrees C, which lowered acetylcholine-like output by approximately 70%. Responses to U46619, at 37 degrees C, were unchanged during the presence of atropine or hyoscine. Acetylcholine is released into the foetal circulation of the human placenta but no evidence could be obtained that it affects villous vascular smooth muscle tone or vasoconstrictor responses.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Changes in lymphocyte status and responsiveness in pregnancy detected by a fluorescent cell probe.
Lymphocyte reactivity assessed by a fluorescent lipophilic probe test of responsiveness to concanavalin A (con A) was shown to differ from normal in early pregnancy. The difference was most marked in multiparas. Abnormal reactivity was detected in the earliest pregnancy examined (5 weeks' gestation) and up to about the 20th week; after 20 weeks, reactivity was normal in all of the multiparas and most of the nulliparas studied. However, in pregnancy induced hypertension (PIH), a disorder of late pregnancy, the same responsiveness as in early pregnancy was found. When unstimulated lymphocytes were examined, abnormal reactivity associated with increased fluorescence was observed in early pregnancy and in PIH, compared with normal late pregnancy, reflecting alteration in lymphocyte membrane phospholipids. It is postulated that pregnancy is associated with sequential change in immunity, disturbance of which may result in immunologically-determined obstetric morbidity.
Adult↗
Antenatal intrauterine diagnosis of fetal thalassaemia.
The results are reported of the intrauterine diagnosis of fetal thalassaemia in 72 pregnant women investigated during the six years from 1977 to 1982. In the majority of cases fetal blood was collected by fetoscopy for globin chain synthesis at 18 to 19 weeks' gestation. Adequate fetal blood samples for the diagnosis of the thalassaemia status of the fetus were obtained in 85% of cases. The technical difficulties associated with fetoscopy and fetal blood collection are discussed, and the maternal and fetal complications of the procedure described.
Blood Chemical Analysis↗
Effects of vasoactive autacoids on the human umbilical-fetal placental vasculature.
Studies have been made of the effects of autacoids on vascular tone of the human perfused fetal umbilical vein and placental lobule. The thromboxane A2 (TxA2)-mimetic substance U46619, 5-hydroxytryptamine and bradykinin were powerful constrictors of the vein. Prostaglandins E2 (PGE2), F2 alpha (PGF2 alpha), adrenaline, noradrenaline, histamine and angiotensin II were much less potent. Venoconstriction caused by U46619, bradykinin and 5-hydroxytryptamine was reduced during inhibition of phospholipase A2 with mepacrine. Responses to U46619 were also reduced after inhibition of cyclo-oxygenase with indomethacin whereas those to bradykinin and 5-hydroxytryptamine were potentiated. In the placenta U46619 was the most potent vasoconstrictor, bradykinin, 5-hydroxytryptamine, angiotensin II, PGE2 and PGF2 alpha being 10-100 times less active. Responses to U46619 were reduced by either mepacrine or indomethacin. Arachidonic acid caused umbilical venoconstriction but vasodilatation in the placenta. Both effects were reduced by indomethacin. Prostacyclin (PGI2) caused vasodilatation in both preparations. It is suggested that TxA2 in the placenta and TxA2, 5-hydroxytryptamine and bradykinin in the umbilical vein could contribute to control of vascular smooth muscle tone. Their vasoconstrictor effects are partly indirect and affected by the concomitant local release of eicosanoids. The results add support to previous conclusions that these autacoids may normally have important influences on blood flow in the fetal extra-corporeal circulation. Agents inhibiting their synthesis, eg non-steroidal anti-inflammatory agents, should only be prescribed during pregnancy with these facts in mind.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Lymphocyte subclasses in pregnancy induced hypertension.
Peripheral blood lymphocyte subclasses were studied by flow cytofluorimetry and monoclonal antibodies in 21 women with Pregnancy Induced Hypertension (PIH), 20 healthy women in their third trimester of pregnancy and in 20 nulliparous, nonpregnant women. The cells were stained with the monoclonal antibodies OKT3, OKT4 and OKT8 to define total T cells, T helper cells (Th) and T suppressor-cytotoxic cells (Ts/c) respectively. B lymphocytes were defined by their surface immunoglobulin. Absolute numbers of total T cells and Ts/c cells were significantly decreased (p less than 0.05) in patients with PIH compared to either control group. The proportion of B lymphocytes was significantly (p less than 0.01) increased and absolute numbers were marginally increased. These findings reflect an immune disturbance which may be of prime importance in the pathogenesis of this disease.
Adolescent↗
Human luteal tissue prostaglandins, 17 beta-estradiol, and progesterone in relation to the growth and senescence of the corpus luteum.
Prostaglandins (PG) E2 and F2 alpha, the 13,14-dihydro-15-keto metabolite of PGF2 alpha, 17 beta-estradiol, and progesterone (P) were measured in luteal tissues obtained from 28 women undergoing abdominal hysterectomy for various benign gynecologic conditions. The highest concentration of PGF2 alpha was found in corpora lutea in the late luteal phase, in which the P concentration was lower than in corpora lutea from earlier phases of the cycle. In postovulatory corpora lutea, PGF2 alpha levels were low, while those of PGE2 and P were high. A positive correlation existed between concentrations of P and PGE2 in luteal tissues throughout the cycle. The results suggest that PGE2 may exert a trophic influence on luteal steroidogenesis and that PGF2 alpha is involved in human luteal regression.
Adult↗
Attenuation by captopril of pressor responses to sympathetic stimuli: effects of procedures reducing activity of the renin-angiotensin system.
Low doses (0.1-1.0 mg/kg) of the converting enzyme inhibitor captopril given intravenously to pithed rats were followed by long lasting falls in systolic and diastolic arterial blood pressures. Concomitantly pressor responses were reduced to either electrical stimulation of the thoraco-lumbar sympathetic outflow or intravenous injection of the ganglion stimulant McNeil-A-343. Positive chronotropic responses of the heart to cardiac nerve stimulation were unchanged after relatively large doses of the drug (3.0 mg/kg). The reductions in arterial blood pressure and pressor responses to McNeil-A-343 caused by captopril persisted following beta-adrenoreceptor blockade, renal sympathectomy or unilateral nephrectomy, but did not occur after acute bilateral nephrectomy nor during sodium and water retention due to unilateral nephrectomy plus subacute administration of desoxycorticosterone and saline. Pressor responses to noradrenaline were reduced after 1.0 mg/kg captopril i.v. whereas those to methoxamine or vasopressin were unaltered after 5.0 mg/kg. It is concluded that in the rat, after elimination of sympathetic tone by pithing, the level of the arterial blood pressure and the magnitude of pressor responses to peripheral sympathetic nerve activation depend on the basal activity of the renin-angiotensin system. This maintains sufficient angiotensin II production to ensure retention of some tone in resistance vessels together with presynaptic augmentation of noradrenaline output at a sympathetic postganglionic nerve endings. The latter effects are abolished after converting enzyme inhibition with captopril, consequent to reduced tissue levels of angiotensin II and perhaps potentiation of the actions of bradykinin.
Animals↗
Adolescent primigravidae and their obstetric performance.
The obstetric performance of adolescent primigravidae in a major metropolitan teaching hospital was analysed retrospectively and found to be similar, if not superior, to that of a control group of primigravidae. This was surprising in view of the late antenatal presentation of the adolescents and their smaller physique. More low birth weight infants, however, were born to adolescent than to older primigravidae, although the perinatal mortality was not increased because of this.
Adolescent↗
Clinical features of eight pregnancies resulting from in vitro fertilization and embryo transfer.
In vitro fertilization (IVF) and embryo transfer (ET) have resulted in the birth of nine babies, including twins. One of the twins had a congenital cardiac malformation and seven of the nine babies were girls. Labor occurred preterm in two pregnancies; and in six delivery was by cesarean section. Plasma human chorionic gonadotropin (hCG), progesterone (P), and estriol (E3) measurements and ultrasonic scans showed no obvious differences from pregnancies resulting from natural conception. Cytogenetic studies from cord blood and histologic examination of the placentas were unremarkable. The theoretic risks of pregnancy following IVF and ET are discussed. Definite conclusions cannot be drawn until a large number of babies are delivered and a long-term follow-up is completed. Initial results from the current small sample are encouraging.
Adult↗
Aggregation of human platelets by amniotic fluid.
Twenty-four amniotic fluid samples were examined for their effects on human platelets. All samples caused irreversible platelet aggregation. The active material precipitated with high-speed ultracentrifugation and was completely inhibited by prior incubation with purified collagenase. The presence of free collagen in amniotic fluid was further confirmed by polyacrylamide-gel electrophoresis and hydroxyproline assays. Beside platelet-aggregating activity, amniotic fluid samples were also shown to significantly shorten the recalcification time of normal plasma. This procoagulant activity appears to be related to the presence of thromboplastin, collagen and other as yet unidentified procoagulant material in amniotic fluid. The presence of activators of platelets and clotting factors in amniotic fluid would account for the strong clot-promoting activity of this fluid. These studies suggest that the ideal management of the coagulopathy of pregnancy should include a combination of anticoagulant and antiplatelet drugs.
Amniotic Fluid↗
Captopril inhibits pressor responses to peripheral sympathetic nerve activation in cats and rats.
1. In cats, under chloralose anaesthesia, captopril (0.1-0.3 mg/kg i.v.) inhibited the potentiation of the pressor effects of the ganglion stimulant McNeil-A-343 caused by intravenous infusion of angiotensin I (0.1 microgram/min). 2. In both cats and rats under chloralose anaesthesia captopril (0.01-1.0 mg/kg i.v.) depressed pressor responses to McNeil-A-343 whilst not modifying those to bilateral occlusion of the carotid arteries, or intravenous injection of the ganglion stimulant dimethylphenylpiperazinium or adrenaline. 3. It is concluded that in the cat and rat captopril depresses cardiovascular responses to sympathetic postganglionic nerve activation, both in the presence and absence of exogenous angiotensin I by an action which is proximal to the terminal synapse.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
Myometrial prostaglandins during the human menstrual cycle.
Prostaglandins E and F (PGE, PGF) and their 13,14-dihydro-15-keto metabolites were measured by radioimmunoassay in myometrium obtained from 27 women during abdominal hysterectomy for benign gynecologic conditions at defined stages of the menstrual cycle. Excepting the late secretory phase, when myometrial PGF concentrations were highest, the myometrial PGE concentration exceeded that of PGF throughout most of the menstrual cycle, especially during the late proliferative phase. The prostaglandin metabolites in myometrium did not fluctuate during the cycle, but their respective ratios with the parent prostaglandins showed changes indicative of increased biosynthesis and/or reduced catabolism of PGF and reduced biosynthesis and/or increased catabolism of PGE during the late secretory phase. The results suggest that PGE is involved in the mechanism of increased myometrial activity in the periovulatory period and that PGF may be important in the initiation of menstruation.
Adult↗
Radioimmunoassay of prostaglandin F2 alpha using sephadex G-75 gel chromatography.
The development of a "bound-free" separation technique and its application to the radioimmunoassay of prostaglandin F2 alpha is described. The method is simple, rapid, free of non-specific binding and could be performed either at 4 degrees C C or at room temperature. A total of 100 tubes could be subjected to "bound-free" separation in 30 min at 4 degrees C. The bound fraction is collected directly into scintillation vials. The total column length was 9.5 cm, of which the bed volume was 2.5 ml. The PGF2 alpha radioimmunoassay incubation volume of 0.3 ml when bedded in required 1.4 ml of elution buffer to elute the antibody-bound fraction. The free fraction was washed out with 4.0 ml of buffer and the columns were ready for further use. A standard curve of high sensitivity (5 pg) and good reproducibility (CV%: intra-assay = 6.54; inter-assay = 9.68) was obtained.
Antigen-Antibody Complex↗