Placental Perfusion Pressure Research Articles

Placental ischemia-upregulated angiotensin II type 1 receptor in hypothalamic paraventricular nucleus contributes to hypertension in rat.

Preeclampsia (PE) is associated with increased angiotensin II sensitivity and poor neurological outcomes marked by temporal loss of neural control of blood pressure. Yet the role of centrally expressed angiotensin II type 1 receptor (AT1R) within the paraventricular nucleus of the hypothalamus (PVN) in the PE model is not understood. In a PE rat model with reduced placental perfusion pressure (RUPP) induced on gestational day 14 (GD14), the PVN expression and cellular localization of AT1R were assessed using immunofluorescence and western blotting. The sensitivity of RUPP to acute angiotensin II infusion was assessed. AT1R was antagonized by losartan (100µg/kg/day) for 5days intracerebroventricularly (ICV). Hemodynamic data and samples were collected on GD19 for further analysis. RUPP upregulated (p < 0.05) mRNA and protein of AT1R within the PVN and lowered (p < 0.05) circulating angiotensin II in rats. RUPP increased neural and microglial activation. Cellular localization assessment revealed that AT1R was primarily expressed in neurons and slightly in microglia and astrocytes. Infusion of 100ng/kg as bolus increased the mean arterial pressure (MAP in mmHg) in both RUPP and Sham. ICV losartan infusion attenuated RUPP-increased MAP (113.6 ± 6.22 in RUPP vs. 92.16 ± 5.30 in RUPP + Los, p = 0.021) and the expression of nuclear transcription factor NF-κB, tyrosine hydroxylase (TH), NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) in the PVN. Our data suggest that centrally expressed AT1R, within the PVN, contributes to placental ischemia-induced hypertension in RUPP rats highlighting its therapeutic potential in PE.

Feasibility of continuous intra-uterine pressure measurements during amnioreduction in twin-to-twin transfusion syndrome therapy

IntroductionThis work explores the feasibility of simultaneous and continuous intra-abdominal, intra-uterine, and arterial blood pressure measurements to examine the hemodynamic perturbation expected during therapeutic amnioreduction and to better understand the protective role of the placenta during that treatment. MethodsPatients with twin-to-twin transfusion syndrome were treated with fetoscopic laser ablation followed by amnioreduction. Intra-abdominal, intra-uterine, and mean arterial pressures were simultaneously recorded during amnioreduction performed in steps of 200 mL. Placental thickness and uterine dimensions were measured before and after amnioreduction by ultrasonography. ResultsUseful pressure recordings were obtained between volume reduction steps and short hands-off periods in four studies. Median amnioreduction volume was 1400 mL corresponding to a median uterine volume reduction of 1121 mL. Mean intra-uterine pressure significantly fell from 24.8 to 13.6 mmHg (p = 0.011) and intra-abdominal pressure significantly decreased from 13.4 to 9.2 mmHg after amnioreduction (p = 0.015). Uterine pressure recordings revealed transient contractions (A, in mmHg) following individual amnioreduction steps, which increased with fractional amnioreduction (F, no dimension) (A = 17.23*F + 11.81; r = 0.50, p = 0.001). DiscussionSimultaneous and continuous measurement of intra-abdominal, intra-uterine, and arterial blood pressures during amnioreduction is feasible. The dynamics reveal transient uterine contractions reaching levels comparable to those seen during childbirth which seem to oppose impending maternal hypovolemia by placental steal at the expense of temporarily reducing placental perfusion pressure and underline the importance of uterine and placental interaction.

995: Maternal central blood pressure is associated with middle cerebral artery dopplers

Our objective was to create maternal cardiac profiles of pregnant women using non-invasive measurements of central BP to identify changes in maternal hemodynamics and the effect on the fetus. This was a prospective cohort study of all pregnancies followed in a single perinatal referral center. Antenatal data was collected for analysis. Central BP was measured non-invasively using the Uscom BP+ device, a supra-systolic oscillometric central BP (cBP) device, which measures BP waveforms peripherally in the arm. The BP+ device calculates central BP and pulse pressure waves using a physics-based model of the arteries between the aorta and the cuff. The Student’s t-test was used to compare categorical means and Spearman rank correlation was used to evaluate correlations between continuous variables. 279 women were recruited for the study. The Uscom BP+ device information was categorized by patient and gestational age (GA) based on ultrasound at the time of the visit. Mean maternal age was 32.4 years (19-54). For first trimester (n=121), the mean central systolic BP was 103.1 mmHg (standard deviation 12.4), the mean central diastolic BP was 67.3 mmHg (10.1), and the mean pulse was 81 bpm (11). For second trimester (n=132), the mean central systolic BP was 100.5 mmHg (12.0), the mean central diastolic BP was 66.7 mmHg (10.8), and the mean pulse was 83 bpm (13). For third trimester (n=39), the mean central systolic BP was 105.8 mmHg (13.1), the mean central diastolic BP was 72.8 mmHg (11.7), and the mean pulse was 91 bpm (9). Both central systolic and diastolic BP were correlated to peripheral systolic and diastolic BP (p<0.01). Central BP was not found to be directly correlated to the estimated fetal weight (EFW) (n=167) (p>0.42). Central BP was negatively correlated to the pulsatility index (PI) for the middle cerebral artery (MCA) (n=19) (p<0.05). Additionally, the MCA PI was found to be positively correlated to the EFW (p<0.05). Non-invasive measurement of maternal central BP likely provides a more accurate indicator of utero- placental perfusion pressure and downstream vascular resistance. We demonstrate that maternal central BP correlates to the MCA PI and, vis-à-vis, EFW.

Abstract 042: Selective Maternal Hepatic Silencing of Angiotensinogen in Reduced Uterine Placental Perfusion Pressure Rats Improves Blood Pressure and Fetal Weights

Women with Preeclampsia (PE), a form of new onset hypertension during pregnancy, exhibit alterations in the renin angiotension system (RAS). These differences include angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA), ANG II sensitivity, and increased oxidation and levels of angiotensinogen (AGT). While antihypertensive drugs are used in pregnancy, their use is associated with reduced fetal growth, and RAS blockade is specifically contraindicated due to fetotoxicity. AGT is the precursor to ANG II and the initial substrate of the RAS pathway. Genetic mutations that result in an over-expression of AGT are strongly associated with hypertension. We have previously shown that siRNA targeting maternal hepatic AGT in a transgenic model of preeclampsia (hAGT x hREN) resulted in lower blood pressure, a 90% reduction in AT1-AA activity, and normalized IUGR. The purpose of the present study is to examine the effect of silencing maternal hepatic AGT on maternal blood pressure and fetal growth in the reduced uterine placental perfusion pressure (RUPP) model of PE. Methods: Pregnant Sprague Dawley rats were divided into 4 groups: normal pregnant (NP, n=7); RUPP (n= 6); RUPP + siRNA (n =7); NP + siRNA (n=7). On day 12 of gestation (GD), siRNA was subcutaneously injected into rats (10mg/kg), GD14 the RUPP surgery was performed, GD18 carotid catheters inserted, and GD19 conscious blood pressure (MAP) and fetal weight was recorded. Results: MAP was elevated in RUPP vs. NP (134±6 vs. 101±4 mmHg, p&lt; 0.05), but was lower in RUPP + siRNA (117±4 mmHg) and unchanged in the NP+siRNA (92±3 mmHg) group compared to NP. Average fetal weights by group were 2.30±0.09 g (NP), 1.89±0.10 g (RUPP), 2.38±0.09 g (NP+siRNA), and 2.12±0.06 (RUPP+siRNA). A one-way ANOVA indicates a significant reduction in pup weights between NP and RUPP, but not NP+siRNA and RUPP+siRNA, indicating administration of siRNA to RUPP rats prevented the decrease in fetal weight. Conclusion: Administration of AGT siRNA to RUPP rats blunts the increase in blood pressure and prevents a decrease in fetal weights in response to placental ischemia and thus could be a potential therapy for management of preeclampsia and other hypertensive disorders of pregnancy. Research Supported by Alnylam &amp; T32HL105324,

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Objectives To assess the degree of sexual dimorphism for Preterm Birth (PTB), Pregnancy Induced Hypertensive Disorders (PIHD) and Gestational Diabetes Mellitus (GDM) in an Australian population. Methods Retrospective population-based study of 574,358 South Australian singleton live births during 1981–2011 in the South Australian Perinatal Statistics Collection of three major adverse pregnancy outcomes (PTB (divided by PTB [birth before 37 weeks] and ePTB [birth before 34 weeks]), PIHD and GDM) in relation to fetal sex. Results There were 295,724 male (51.5%) and 278,634 (48.5%) female neonates (sex-ratio 1.06). Among all pregnancies there was a significant male dominance in pregnancies complicated by PIHD (RR 1.053, 95%-CI 1.034–1.072), PTB (PTB – RR 1.115, 95%-CI 1.092–1.139 & ePTB – RR 1.151, 95%-CI 1.104–1.199) and GDM (RR 1.042, 95%-CI 1.011–1.074). The pattern for PIHD by gestational age was markedly different (Fig. 1). Preterm PIHD showed a significant female dominance [RR’s ranging from 0.686, 95%-CI 0.581–0.811 (25–29 weeks) to 0.925, 95%-CI 0.870–0.982 (34–36 weeks)], while term PIHD showed a significant male dominance [RR 1.064, 95%-CI 1.037–1.093 (37–39 weeks) and RR 1.074, 95%-CI 1.044–1.105 (40–42 weeks)]. Conclusions This large South Australian cohort confirms the presence of marked sexual dimorphism for PTB, PIHD and GDM. The striking associations of male fetal sex with PTB and female sex with preterm PIHD could indicate that a certain degree of placental dysfunction in the male fetus would lead to PTB while the female fetus may be able to temporarily improve intrauterine life by increasing maternal blood pressure and thereby placental perfusion pressure with the attendant risk of PIHD. Disclosures P.E. Verburg: None. G. Tucker: None. W. Scheil: None. J.H. Erwich: None. C.T. Roberts: None. G.A. Dekker: None.

Effect of propofol on human fetal placental circulation

Background Propofol is an alternative to thiopental for induction of general anaesthesia for cesarean section. It crosses the placenta and induces vasodilatation of isolated vessels and may therefore alter fetal placental vascular resistance. The direct effect of propofol on the fetal placental circulation was studied in vitro. The actions of propofol on vasoconstrictive effects induced by angiotensin II (Ang II), bradykinin (BK), prostaglandin F 2α (PGF 2α) and potassium chloride (KCl) were evaluated. Methods Full-term healthy human placentas (n = 48) were perfused with modified Tyrode’s solution using a pulsatile pump. Placental perfusion pressure was measured in response to injection of Ang II, BK, KCl and PGF 2α before and after perfusion with propofol (1.7 × 10 −5 and 5.6 × 10 −5 M). Results BK, Ang II, KCl and PGF 2α induced a dose-dependent increase in placental perfusion pressure. Propofol induced a concentration-dependent decrease in placental perfusion pressure, but this was not observed with the propofol solvent (Intralipid). Propofol, but not Intralipid, reduced the vasoconstrictor effects of BK, KCl and PGF 2α, while the effect of Ang II was not changed. The effect of KCl was abolished in placentas perfused with Ca 2+-free solution, while the effect of Ang II was not altered. Conclusions Propofol induced vasodilatation and inhibited the vasoconstrictive effects of BK and PGF 2α, in the human placenta. These findings suggest that propofol may not reduce fetal placental blood flow. Since propofol reduced the vasoconstricting effect of KCl but not that of AngII, we propose that the vasodilatory effect of propofol in the human placenta involves inhibition of Ca 2+ channels.

Maternal Nicotine Exposure: Long-Term Effect on Lung Integrity in the Offspring

Nicotine occurs in tobacco smoke. It is a habit forming substance and is prescribed by health professionals to assist smokers to quit smoking. It is rapidly absorbed from the lungs of smokers. It crosses the placenta and accumulates in the developing fetus. Nicotine induces formation of oxygen radicals and at the same time also reduces the anti-oxidant capacity of the lungs. Nicotine and the oxidants cause point mutations in the DNA molecule thereby changing the program that controls lung growth and maintenance of lung structure. The data available indicate that maternal nicotine exposure induces a persistent inhibition of glycolysis and a drastic increased cAMP level. These metabolic changes are thought to contribute to the faster aging of the lungs of the offspring of mothers that are exposed to nicotine via the placenta and mothers milk. The lungs of these animals are more susceptible to damage as shown by the gradual deterioration of the lung parenchyma. The rapid metabolic and structural aging of the lungs of the animals that were exposed to nicotine via the placenta and mothers milk, and thus during phases of lung development characterized by rapid cell division, is likely due to “programming” induced by nicotine and not by inadequate placental perfusion pressure and nutrient supply. It is therefore not advisable to use nicotine during gestation and lactation. Keywords: Lung development, programming, premature aging, nicotine

PLACENTAL HEME OXYGENASE ACTIVITY REDUCTION IS ASSOCIATED WITH HYPERTENSION IN PREGNANT RATS

Reduction in the placental perfusion pressure has long been thought to underlie preeclampsia (PE). It has also been demonstrated that inhibition of heme oxygenase (HO) activity in isolated placenta increases placental perfusion pressure. This finding suggests that the HO‐CO system is involved in regulating blood flow to this organ. However, it is unknown whether the reduction of placental HO activity produces hypertension during gestation, which is a common feature in PE. Therefore, the aim of this study was to determine whether administration of an HO inhibitor during gestation induces an elevation in blood pressure (BP) and whether the hypertension is associated to a reduced placental HO activity. The HO inhibitor, stannous mesoporphyrin (SnMP; 50 micromol/kg i.p) or vehicle (sodium carbonate) were administered to virgin (n=6) and pregnant rats (n=7) at day 14 of gestation. BP was measured 5 days later in conscious rats. SnMP increased (p&lt;0.01) BP in pregnant rats (114 ± 1 vs 100 ± 2 mmHg) but had no effect in virgin rats (121 ± 2 vs 124 ± 3 mmHg). This increase was associated to a reduction in placental HO activity (10.4 ± 0.5 vs 6.9 ± 0.2 ng/bilirubin/μg protein/h, p&lt;0.05) and an important fetal reabsorption (4.0 ± 0.7 vs 1.0 ± 0.3, p&lt;0.05), indicating possible placental ischemia. These results suggest that the HO‐CO system may play an important role in the development of PE.

The effect of nicotine on in vitro placental perfusion pressure

Cigarette smoking throughout pregnancy is associated with several negative outcomes, of which an increased incidence of intra-uterine growth restriction (IUGR) is most pronounced. Gestationally age-matched infants born to smoking mothers are, on average, 200 g lighter at birth, per pack smoked per day. The mechanisms and specific tobacco compounds responsible for the increased risk of IUGR among smokers have yet to be identified; however, it is widely accepted that smoking women have compromised placental perfusion throughout gestation due to the vasoconstricting effect of nicotine on uterine and placental blood vessels. Despite the universal acceptance of this theory, very little work has been completed to date examining the vasoactive properties of nicotine within the human placenta. The objective of this study was to determine the effect of nicotine on placental vascular function. Normal-term human placentae were obtained after elective cesarean sections. An in vitro placental perfusion system was used; increasing doses of nicotine (20-240 ng/mL) were added to either the maternal (n = 5) or fetal (n = 3) circulation. The basal feto-placental perfusion pressure was 39.87 +/- 4.3 mmHg and was not affected by nicotine. This finding supports the hypotheses that nicotine does not directly affect placental microvascular function and that any contribution to fetal growth restriction is likely at the level of placental function (i.e., amino acid transport) and (or) uterine vascular function.

The effect of cholic acid on placental artery perfusion pressure in the ex vivo placental cotyledon model

The effect of cholic acid on placental artery perfusion pressure in the ex vivo placental cotyledon model

Autonomic dysfunction may be an under-recognized cause of female fertility disorders

Female conditions of impaired fertility comprise a heterogeneous group of disorders that are attributed to various anatomic, hormonal and immunologic disturbances. We hypothesize that autonomic dysfunction may be a previously unrecognized factor in female fertility disorders. Emerging physiologic and molecular evidence suggests that autonomic balance varies during normal menstrual cycles with a shift to sympathetic bias during the luteal phase. Furthermore, many diseases associated with autonomic dysfunction show catamenial variations in patterns consistent with a shift to sympathetic bias occurs during the second half of normal menstrual cycles. The shift to sympathetic bias during the normal luteal phase may be an evolutionary adaptation to address the immunologic and physiologic demands for successful implantation and gestation. Through direct modulation of the lymphoid system and activation of the cortisol pathway, sympathetic bias promotes a shift to relative T helper (Th)-2 biased immunity which may favor maternal tolerance of the embryo by attenuating Th-1 mediated interference of implantation. Indeed, a growing body of evidence has implicated abnormal Th balance in fertility disorders, but the link has been attributed to factors other than autonomic function, such as hormonal factors. After implantation, maternal sympathetic bias may further support gestation through physiologic changes necessary to maintain placental perfusion pressure. We propose that insufficient shift to sympathetic bias during the luteal phase, which manifests in inadequate shift towards Th-2 bias and down-regulation of Th-1 function, may be the mechanism of impaired fertility in certain patients. Our hypothesis portends new potential methods to treat fertility disorders by modulating autonomic balance.

Carbon Monoxide Decreases Perfusion Pressure in Isolated Human Placenta

Carbon monoxide (CO) is one of the metabolites formed via heme oxidation catalysed by the enzyme heme oxygenase (HO). Endogenous formation of CO, mediated by HO, has been noted in both placental and umbilical vessels. In blood vessels from different mammalian sources, it has been proposed that the vasodilator effect of CO is mediated via stimulation of soluble guanylyl cyclase (sGC) and consequent increased cGMP formation. The purpose of the present study was to determine the effect of exogenous CO on placental cotyledon perfusion pressure and to determine the role of sGC in the CO-induced decrease of perfusion pressure using the in vitro human placental perfusion preparation. A thromboxane A2 mimetic (U46619) was added to the foetal perfusion medium to constrict the placental blood vessels. Carbon monoxide was added to the foetal perfusion medium in increasing concentrations to determine its effect on placental perfusion pressure. Carbon monoxide produced a concentration-dependent decrease in placental perfusion pressure. The addition of ODQ, a sGC inhibitor, attenuated the CO-induced decrease in placental perfusion pressure, while addition of YC-1, an activator of sGC, augmented the CO-induced decrease in placental perfusion pressure. The data indicate that CO causes vasorelaxation of placental resistance blood vessels, in large part, via activation of sGC.

Fetal Placental Vascular Responses to Corticotropin-Releasing Hormone in Vitro. Effects of Variation in Oxygen Tension

In this study, using the human placenta perfused in vitro with Krebs' bicarbonate solution, we have examined the effects of changes in oxygen tension on the vasoreactivity of fetal placental blood vessels to corticotropin releasing hormone (CRH). Vasodilatory responses to human synthetic CRH were measured during sub-maximal vasoconstriction of the fetal placental circulation with prostaglandin F2α(PGF2α) (1–100μm). Decreases in fetal placental arterial perfusion pressure (FAP) were obtained with CRH under conditions of high oxygen or low oxygen tension, ≥450mmHg and ≤50mmHg, respectively. Secretion of CRH into the maternal and fetal placental circulations was measured during changes in oxygen tension in normal placentae and placentae from abnormal pregnancies complicated by pre-eclampsia.The change from high to low oxygen perfusion resulted in a small increase in the basal perfusion pressure (21±3.6 to 28.3±2.6mmHg; (P≤ 0.001, Student's paired t -test). During high oxygen perfusion, CRH (0.3–3000p m) caused a concentrationdependent reduction of the PGF2αinduced increase in FAP. However, during low oxygen perfusion, the vasodilatory effects of CRH were completely inhibited (P≤ 0.05, regression analysis, ANOVA). The effect of the NO synthase inhibitor l -nitro-ω-arginine methyl ester (l -NAME, 1–100μm), on basal FAP during high and low oxygen conditions was also established. Low oxygen perfusion significantly attenuated l -NAME-induced increases in perfusion pressure (P≤ 0.05, regression analysis, ANOVA). Low oxygen perfusion was associated with an increase in CRH secretion into the maternal but not fetal circulation. CRH release into either the maternal or fetal circulations of abnormal placentae were not significantly different from normal controlsIn conclusion CRH-induced vasodilatation of the fetal placental vasculature in vitro is inhibited during low oxygen perfusion. This effect may be related to reduced NO production. Reduced CRH induced vasodilation is associated with increased secretion of the CRH into the maternal but not fetal circulation.

Hemeoxygenase expression in human placenta and placental bed implies a role in regulation of trophoblast invasion and placental function.

The purpose of this study was to examine the expression of hemeoxygenases HO-1 and HO-2, which are responsible for the production of carbon monoxide (CO), in the human placenta and placental bed and to determine the role of inhibitors of HO on placental perfusion pressure. We hypothesized that HO is expressed within the placenta and that invading cytotrophoblast cells (CTB) express HO isoforms. The expression of HO-1 and HO-2 was studied on placenta and placental bed biopsies, obtained using a transcervical sampling technique, from normal human pregnancies between 8 and 19 wk gestation and at term. In the placenta, HO-2 immunostaining was prominent in syncytiotrophoblast in the first trimester and reduced toward term (P<0.0005). HO-2 endothelial immunostaining was weak in the first trimester, but increased by term (P<0.0005). Within the placental bed, HO-2 was expressed by CTB in cell columns, the cytotrophoblast shell, and cell islands. Both intravascular CTB and interstitial CTB expressed HO-2. HO-1 immunostaining was low in the placenta but intense on the CTB within the placental bed. A striking feature was the absence of HO-1 from the proximal layers of cell columns, with strong expression on the more distal CTB layers of the cell columns. In placental perfusion studies, a significant dose-dependent increase in perfusion pressure was observed in the presence of zinc protoporphyrin, an inhibitor of HO. These results suggest a role for CO in placental function, trophoblast invasion, and spiral artery transformation. Hemeoxygenase expression in human placenta and placental bed implies a role in regulation of trophoblast invasion and placental function.

In vitro effect of bioactive natriuretic peptides on perfusion pressure in placentas from normal and pre-eclamptic pregnancies.

The number of placental vascular guanylate-coupled receptors. corresponding to bioactive natriuretic peptide receptors is greater in preeclampsia. but there are no clear data about atrial natriuretic peptide (ANP) concentration in preeclampsia. The influence of various doses of ANP and urodilatin (URO) on placental perfusion pressure in preeclampsia was investigated by perfusing 16 human placentas in vitro. The placental vessels were submaximally preconstricted by continuous infusion of N-omega-nitro-L-arginine (NOLA). Perfusion pressure was measured continuously. Over 180 min various doses of alphaANP or URO were administrated (25, 50, 100, 200 nmol/l, 2 min increments). The effects of pretreatment with the guanylate cyclase inhibitor, LY 83583 was also examined. We found that ANP and URO attenuated NOLA-induced vasoconstriction, that URO given in higher doses produced stronger vasocilation than ANP, and that the mean decrease of perfusion pressure was higher in preeclampsia. The possibility of a non cGMP-mediated pathway of ANP and URO action should be considered.

Adrenocorticotropin causes vasodilatation in the human fetal-placental circulation.

During human pregnancy, ACTH is produced by both the placenta and fetal pituitary. ACTH has been shown to cause vasodilatation in the adrenal cortex in vitro. In this context we have investigated the vasoactive effects of ACTH in the human fetal-placental circulation. Single lobules of term human placentas were bilaterally perfused in vitro with Krebs solution (maternal and fetal, 5 mL/min; 95% O2-5% CO2; 37 C; pH 7.3), and changes in fetal placental arterial perfusion pressure (FAP) were measured. ACTH (40-4000 pmol/L; n = 5) caused a dose-dependent reduction of both KC1 and PGF2alpha-induced increases in FAP in the fetal placental circulation. The reductions were of a similar magnitude in the presence of either constrictor agent. ACTH was 187.4 (95% confidence limits, 162.7-215.9) times more potent than prostacyclin (PGI2; 1.2-1180 nmol/L; n = 6), which is a known vasodilator of the fetal-placental circulation. The threshold concentrations for ACTH and PGI2 were 40 pmol/L and 1.2 nmol/L, respectively. ACTH-induced reductions in PGF2alpha-induced increases in FAP in the fetal placental circulation were not inhibited by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (100 micromol/L; n = 5), the cyclooxygenase inhibitor indomethacin (3 micromol/L; n = 5), or a guanylate cyclase inhibitor LY83583(1 micromol/L; n = 5). The inhibitory effect of ACTH was attenuated by the antagonist, ACTH-(7-38) (240 pmol/L; n = 4), and a polyclonal ACTH antiserum (1:1000 dilution; n = 4). We have demonstrated that ACTH causes a reduction in fetal placental vascular resistance in the human fetal-placental circulation in vitro. The mechanism by which it exerts these effects has not been defined, but neither nitric oxide nor PG-mediated pathways appear to be involved.

Effects of captopril on the human foetal placental circulation: an interaction with bradykinin and angiotensin I.

1. The mechanism underlying the foetal toxicity induced by captopril is not well understood. Since bradykinin and angiotensin II appear to be important in the regulation of the placental circulation, experiments were performed to assess the effects of captopril on the vascular actions of these peptides on the human foetal placental circulation. 2. Full-term human placentas, obtained from normal pregnancy, were perfused with a modified Tyrode solution bubbled with O2 using a pulsatile pump. The placental perfusion pressure was measured with a Statham pressure transducer and recorded continuously on a Hewlett-Packard polygraph. 3. Bradykinin (0.1, 0.3 and 1.0 nmol) injected into the placental arterial circulation produced an increase in placental perfusion pressure in all experiments. This effect of bradykinin was significantly inhibited by indomethacin (3 x 10(-7) M). 4. Captopril (10(-7) M) significantly potentiated the pressor effect of bradykinin on the human placental circulation (n = 6). This effect of captopril was reversed by indomethacin (3 x 10(-7) M). 5. Angiotensin I (n = 6) and angiotensin II (n = 6), injected into the placental arterial circulation, both produced dose-dependent increases in placental perfusion pressure. The dose-response curves to angiotensin I (n = 6) were significantly displaced to the right by captopril in a concentration-dependent manner. 6. We suggest that the toxic effects of captopril on the foetus, rather than reflecting an inhibition of angiotensin II formation, may instead be related to a potentiation of the vasoconstrictor effect of bradykinin on the foetal placental circulation, thereby reducing blood flow and causing foetal damage. The reasons for this are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal response to carbon dioxide pneumoperitoneum in the pregnant ewe

To determine the effects of maternal abdominal carbon dioxide (CO2) insufflation on placental blood flow and fetal blood gas measurements in the pregnant ewe. Five time-bred ewes at 110 days' gestation were surgically prepared with maternal and fetal catheters placed for subsequent measurement of vascular pressures, blood gas tensions, and placental blood flows. On surgical recovery day 3, the ewe was anesthetized, placed on her right side, intubated, and manually ventilated to maintain a constant maternal carbon dioxide pressure (PCO2) range (37.1 +/- 3.3 mmHg) for the duration of the experiment. The maternal abdomen was inflated with CO2 to maintain an intraabdominal pressure of 20.7 +/- 0.6 mmHg. Maternal and fetal blood flows and blood gases were determined at 30 minutes of ventilation, 60 minutes of insufflation, and 40 minutes of desufflation. Simultaneous maternal and fetal organ blood flows were determined using the radioactive microsphere technique. Maternal perfusion pressure fell 22% (P = .01) in response to insufflation, whereas pressure in the inferior vena cava rose 53% (P = .003). Maternal placental blood flow fell to 61% (P = .002) of control. Seventy-seven percent of this blood-flow change was in response to the decreased perfusion pressure, with 23% resulting from an increased placental vascular resistance of 32% (P = .02). Maternal blood gas values did not change with insufflation or desufflation. Despite the marked decrease in maternal placental blood flow, the fetal placental perfusion pressure and blood flow, pH, and blood gas tensions were unaffected by insufflation or desufflation. The sheep fetus has sufficient placental flow reserves or compensatory responses to maintain adequate gas exchange during a 1-hour, 20 mmHg maternal pneumoperitoneum. Laparoscopic surgical procedures may prove to be a safe alternative to laparotomy during pregnancy.

The effects of atrial natriuretic factor and angiotensin II on placental perfusion pressure in the ex-vivo cotyledon model

The effects of atrial natriuretic factor and angiotensin II on placental perfusion pressure in the ex-vivo cotyledon model

The effects of atrial natriuretic factor and angiotensin II on placental perfusion pressure in the ex-vivo cotyledon model

The effects of atrial natriuretic factor and angiotensin II on placental perfusion pressure in the ex-vivo cotyledon model