Arteries In Pregnancy Research Articles

Comparison of Doppler Flow Parameters of Foetal Middle Cerebral Artery in Pregnancy with Gestational Diabetes versus Normal Pregnancy: A Cohort Study

Comparison of Doppler Flow Parameters of Foetal Middle Cerebral Artery in Pregnancy with Gestational Diabetes versus Normal Pregnancy: A Cohort Study

Unilateral Absent Pulmonary Artery in Pregnancy: A Case Report and Systematic Literature Review.

Unilateral absence of a pulmonary artery (UAPA) is a rare congenital malformation associated with hemoptysis, pulmonary hypertension, and infection. Little is known about the impact on pregnancy outcomes. We sought to synthesize the existing literature on pregnancy outcomes in patients with maternal UAPA. We report a case of maternal UAPA and performed a systematic review of the existing literature. Articles in English reporting pregnancy outcomes among women with unilateral absence or hypoplasia of the pulmonary artery were included. Articles were reviewed at the abstract level and, if eligible, at the full-text level by two independent reviewers with disagreements adjudicated by a third reviewer. Data were abstracted by two independent reviewers. Outcomes of interest were mode of delivery, gestational age at delivery, intensive care admission, maternal death, and length of stay. Summary statistics for each outcome are presented. We identified 14 studies, including the presented case, reporting outcomes in 22 pregnancies impacted by maternal UAPA. Median age at diagnosis was 21 years. Concurrent cardiac comorbidities were reported in 6/13 (46.2%) with pulmonary hypertension in 5/20 (25%) of cases where this information was reported. We observed high rates of preterm birth (4/12, 33.3%), cesarean delivery (10/15, 66.7%), and operative vaginal delivery (2/5, 40.0%). There was one maternal death occurring in the immediate postpartum period for a mortality rate of 4.5%. Our study provides a comprehensive review of existing literature on maternal UAPA. Our findings suggest increased rates of adverse outcomes and underscore the importance of early diagnosis, identification of pulmonary hypertension, and multidisciplinary care. · There may be increased adverse outcomes in maternal UAPA.. · Concurrent cardiac abnormalities are common in maternal UAPA.. · Early diagnosis, identification of pulmonary hypertension, and multidisciplinary care are important..

Doppler Indices of the Uterine, Umbilical and Fetal Middle Cerebral Artery in Diabetic versus Non-Diabetic Pregnancy: Systematic Review and Meta-Analysis.

Background and Objectives: The aim of this study was to assess the differences in Doppler indices of the uterine (Ut), umbilical (UA), and middle cerebral artery (MCA) in diabetic versus non-diabetic pregnancies by conducting a comprehensive systematic review of the literature with a meta-analysis. Materials and Methods: PubMed, Web of Science, and SCOPUS were searched for studies that measured the pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio index (S/D ratio) of the umbilical artery, middle cerebral artery, and uterine artery in diabetic versus non-diabetic pregnancies. Two reviewers independently evaluated the eligibility of studies, abstracted data, and performed quality assessments according to standardized protocols. The standardized mean difference (SMD) was used as a measure of effect size. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated by means of funnel plots. Results: A total of 62 publications were included in the qualitative and 43 in quantitative analysis. The UA-RI, UtA-PI, and UtA-S/D ratios were increased in diabetic compared with non-diabetic pregnancies. Subgroup analysis showed that levels of UtA-PI were significantly higher during the third, but not during the first trimester of pregnancy in diabetic versus non-diabetic pregnancies. No differences were found for the UA-PI, UA-S/D ratio, MCA-PI, MCA-RI, MCA-S/D ratio, or UtA-RI between diabetic and non-diabetic pregnancies. Conclusions: This meta-analysis revealed the presence of hemodynamic changes in uterine and umbilical arteries, but not in the middle cerebral artery in pregnancies complicated by diabetes.

Doppler Indices of the Fetal Middle Cerebral and the Umbilical Arteries in Pregnancies at High Risk Followed Up for Suspected Fetal Growth Restriction

Background: Fetal growth restriction is related to compromised perinatal outcomes. The screening and prevention tools for fetal growth restriction like Doppler indices in high-risk groups compared with general antenatal populations. An evaluation of the correlation between Doppler indices and placental weight and birth weight of the neonate at term pregnancy in high-risk pregnancies is essential. For the early detection of fetal growth limitations in high-risk pregnancies, sensitive screening techniques are few. Objectives: To determine the most accurate indicator for predicting a poor perinatal outcome or intrauterine growth restriction by comparing and correlating the modifications in Doppler ultrasound studies of fetal circulation in general pregnant women with those of high-risk patients both with and without intrauterine growth retardation. Study design: A cross-sectional research including 81 healthy pregnancies and 19 high-risk patients at 31–40 weeks of gestation was conducted. The pulsatility index (PI) of the middle cerebral artery (MCA), the umbilical artery (UA), and the MCA PI to UA PI ratio were all analyzed. We compared the Doppler indices' mean values. Then these values were correlated with placental weight and birth weight of the offspring. Results: A significantly low birth weight and less fetoplacental ratio and placental coefficient ratio were found in high-risk cases than in normal pregnant women (P <0.05). A strong positive relationship was observed between the middle cerebral artery pulsatility index and placental weight, while negative relationship between the pulsatility index of the middle cerebral artery and the Feto-placental ratio (P < 0.05). In addition, a positive association was found between the pulsatility index of the middle cerebral artery and placental coefficient, whereas a negative correlation was observed between the Cerebro-placental ratio and Feto-placental ratio in high-risk cases (P <0.05). Conclusion: Low birth weight can be predicted using Doppler indices since there is a definite correlation between it and unfavorable perinatal outcomes. KEY WORDS: Placenta, birth weight, Doppler indices, Middle cerebral artery pulsatility index, Umbilical artery pulsatility index.

Challenges and outcomes of pregnancy in an uncorrected Tetralogy of Fallot with pulmonary atresia and major aorta-pulmonary collateral arteries (MAPCA): a case report

BackgroundTetralogy of Fallot is a severe type of congenital heart disease (CHD) and one of the leading indirect causes of mortality & morbidity among women with CHD. We came across a rare case of an uncorrected Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries in pregnancy. Case presentationWe are reporting the challenges in managing a pregnancy of 25-years-old G3 P0110, previous one stillbirth and who was diagnosed to have congenital heart disease during pregnancy following spontaneous abortion.ConclusionsThis case report highlights the role of multidisciplinary care in managing such a high risk case. It also emphasizes the role of cardiac examination of every woman before pregnancy so that definitive treatment or optimization can be done in time for a better outcome.

Tadalafil Effect on Impedance to Flow in the Umiblical and Fetal Middle Cerebral Arteries in Pregnancies at High Risk for Fetal Growth Restriction

Tadalafil Effect on Impedance to Flow in the Umiblical and Fetal Middle Cerebral Arteries in Pregnancies at High Risk for Fetal Growth Restriction

Effect of prophylactic balloon occlusion of internal iliac artery in pregnancies complicated by placenta previa and accreta

BackgroundPlacenta previa and accreta are serious obstetric conditions that are associated with a high risk of intraoperative massive hemorrhage, the prophylactic intravascular balloon occlusion technique is increasingly used in managing uncontrolled hemorrhage in cesarean section (CS). We aim to examine the clinical effectiveness of prophylactic balloon occlusion of the internal iliac artery (PBOIIA) during CS in improving maternal outcomes for patients with placenta previa and accreta.MethodsA total of 420 women with placenta previa and accreta who underwent CS from January 2014 to December 2018 were included retrospectively. Patients were divided into balloon group in which patients had PBOIIA (n = 248) and the control group in which patients did not have PBOIIA (n = 172). Meanwhile, we performed a subgroup analysis in whether taking parallel transverse uterine incision (PTUI) surgery. Information on conditions of patients and newborns, perioperative blood indicators, surgical outcomes were collected.ResultsMedian estimated blood loss (mEBL) was 2200 mL in the balloon group and 2150 mL in the control group respectively, there was no significant difference between two-groups comparison (P > 0.05), and the rate of patients with hysterectomy was also has no difference between the two groups (36.3% verus 35.5%, P > 0.05), while there is a significant difference between two groups in the amount of PRBCs transfused [3 (0–31.5) verus 3 (0–39), P <0.05], moreover, the proportion of PRBCS> 8 units in the balloon group is significantly lower than that in control group (11.29% verus 23.26%, P <0.05).. However, the total hospitalization costs (45,624.4 ± 11,061.9 verus 37,523.1 ± 14,662.2, CYN) and surgery costs (19,910.6 ± 2622.6 verus 11,850.5 ± 3146.1, CYN) in balloon group were significantly higher than those in control group (P < 0.05). Subgroup analysis showed PTUI surgery had no significant differences in EBL (P >0.05), but it could significantly decrease hysterectomy rates (P <0.05).ConclusionsPBOIIA has no significant effect on reducing intraoperative EBL and hysterectomy rate in patients with placenta previa and accreta. and although it could reduce the intraoperative PRBCs in patients with massive hemorrhage, it significantly increases the financial cost for patients. Therefore, PBOIIA should not be routinely recommended to patients with placenta previa and accreta.

Life saved and a lesson learned-anomalous origin of the left coronary artery from pulmonary artery in pregnancy

Anomalous origin of the left coronary artery from pulmonary artery constitutes 0.5% of all CHD (Boutsikou M, Shore D, Li W, et al, Int J Cardiol 261: 49-53, 2018). Fifteen percent survive into adulthood undiagnosed and 90% present with sudden death (Yau JM, Singh R, Halpern EJ, Fischman D, Clin Cardiol 34: 204-210, 2011; Alexi-Meskishvili V, Berger F, Weng Y, Lange PE, Hetzer R, J Card Surg 10: 309-315, 1995). We describe an enigmatic case of a 29-year-old female who presented after an aborted cardiac arrest and was diagnosed with anomalous origin of the left coronary artery from pulmonary artery.

Ryanodine receptor subtypes regulate Ca2+ sparks/spontaneous transient outward currents and myogenic tone of uterine arteries in pregnancy.

Our recent study demonstrated that increased Ca2+ sparks and spontaneous transient outward currents (STOCs) played an important role in uterine vascular tone and haemodynamic adaptation to pregnancy. The present study examined the role of ryanodine receptor (RyR) subtypes in regulating Ca2+ sparks/STOCs and myogenic tone in uterine arterial adaptation to pregnancy. Uterine arteries isolated from non-pregnant and near-term pregnant sheep were used in the present study. Pregnancy increased the association of α and β1 subunits of large-conductance Ca2+-activated K+ (BKCa) channels and enhanced the co-localization of RyR1 and RyR2 with the β1 subunit in the uterine artery. In contrast, RyR3 was not co-localized with BKCa β1 subunit. Knockdown of RyR1 or RyR2 in uterine arteries of pregnant sheep downregulated the β1 but not α subunit of the BKCa channel and decreased the association of α and β1 subunits. Unlike RyR1 and RyR2, knockdown of RyR3 had no significant effect on either expression or association of BKCa subunits. In addition, knockdown of RyR1 or RyR2 significantly decreased Ca2+ spark frequency, suppressed STOCs frequency and amplitude, and increased pressure-dependent myogenic tone in uterine arteries of pregnant animals. RyR3 knockdown did not affect Ca2+ sparks/STOCs and myogenic tone in the uterine artery. Together, the present study demonstrates a novel mechanistic paradigm of RyR subtypes in the regulation of Ca2+ sparks/STOCs and uterine vascular tone, providing new insights into the mechanisms underlying uterine vascular adaptation to pregnancy.

Effects of sildenafil citrate on impedance to flow in the umbilical and fetal middle cerebral arteries in pregnancies at high risk for fetal growth restriction

Objective: To assess whether sildenafil citrate improves blood flow in fetal um- bilical arteries and middle cerebral arteries in pregnancies at high risk for fetal growth restriction. Methods: A quasi-experimental study was carried out at the Department of Ob- stetrics and Gynecology, Suez Canal University Hospital in Ismail- ia over the period from June 2017 to April 2018. Trans-abdominal obstetric ultrasonography (U/S) was done for 30 pregnant women aged24 to 35 years, gestational age ranged between 33- 36 weeks, at high risk for fetal growth restriction (mild pre-eclampsia, diabetes mellitus, history of previous pregnancy with a small for gestational age, stillbirth, severe pre-eclampsia or pregnancies with abnormal umbilical artery indices-above 90th centile). Fetal umbilical and middle cerebral artery blood flow Doppler indices were determined before and 2 and 6 hours after ingestion of sildenafil citrate 20 mg tablet. Results: There was a statistically significant decrease in umbilical artery Dop- pler indices before, two hours and six hours following sildenafil ci- trate therapy in the studied patients (P<0.05) and a statistically signif- icant increase in middle cerebral artery Doppler indices before, two hours and six hours following sildenafil citrate therapy in the studied patients (P<0.05). Conclusions: Sildenafil citrate significantly increases blood flow in the umbilical arteries and normalizes blood flow in fetal middle cerebral arteries in pregnancies at high risk for fetal growth restriction thereby restoring a normal fetal circulation and corrects the “brain sparing” adaptive mechanism.

Maternal Serum Matrix Metalloproteinase 14 (MMP14) in Early Onset Preeclampsia and Normal Pregnancy

Matrix Metalloproteinases 14 presumably play for cytotrophoblast migration and invasion of the uterine wall and in the remodeling of the spiral arteries in pregnancy. Inadequate trophoblastic invasion leads to an inappropriate vascular remodeling, which generates conditions of hypoxia and increased oxidative stress in the placenta early onset preeclampsia. Therefore, it is particularly important to investigating whether MMP14 altered and can be used as biomarker of preeclampsia. There have been no studies done to measure MMP14 in serum maternal between early onset preeclampsia and normal pregnancy The purpose of this study was to analyse whether maternal serum matrix metalloproteinases 14 levels differ in early onset preeclampsia and uncomplicated pregnancies. This crosssectional study was carried out in 20 subjects with early onset preeclampsia and 20 subjects of normotensive pregnant women range 24 up to 34 weeks of gestation. The study was conducted in Margono Hospital Purwokerto, Indonesia. Level of MMP 14 was measured in maternal serum using an enzyme-linked immunosorbent assay (ELISA). The mean difference was statically analysed by independent samples T-test and ROC curve to determine sensitivity and specificity of MMP 14.Women age, gestational age, parity and body mass index showed a non significant difference between both groups. In this study level MMP 14 in serum was higher in pregnant women with preeclampsia compared to the normotensive ( 266.41 vs 46.80 pg/dl ; p&lt;0.00). Moreover, the area under curve of serum MMP 14 was 0.936, standard error 0.043, p&lt;0.00. The optimal cut-off value of serum MMP at 110.73 pg/dl showed a high diagnostic value in preeclampsia with a sensitivity of 90 % and a specificity of 90%. Maternal serum MMP 14 was higher in preeclampsia and the important finding is the MMP 14 probably become a marker to predict early onset preeclampsia.

Doppler Sonography of Uterine Arteries in Pregnancy as a Marker of Preeclampsia

Doppler Sonography of Uterine Arteries in Pregnancy as a Marker of Preeclampsia

244: The effect of maternal hyperoxygenation on fetal pulmonary vasoreactivity and on blood flow patterns in the umbilical artery and middle cerebral artery in pregnancy

We sought to evaluate the changes in fetal pulmonary artery, umbilical artery and middle cerebral artery Doppler waveforms in response to maternal hyperoxygenation. Nineteen pregnant women with a singleton gestation in the third trimester were prospectively recruited to the study. The protocol for the investigation was approved by the National Ethics Committee and the Health Products Regulatory Authority (HPRA) in Ireland. Informed consent was signed by all participants. Blood flow velocity waveforms were recorded during periods of fetal quiescence. A comprehensive fetal echocardiogram was performed on all subjects. Pulsatility index (PI), acceleration time (AT), and ejection time (ET) were taken within the proximal portion of the fetal main pulmonary artery (PA). AT:ET was used to assess pulmonary vascular resistance (PVR). The sample volume gate was adjusted to 3 mm, and the angle of insonation was maintained at ≤ 15°. Umbilical artery (UAD) and middle cerebral artery (MCA) PIs were also obtained. Measurements were taken at baseline and repeated immediately following maternal hyperoxygenation with 60% FiO2 for a 10-minute duration. Values are presented as medians [Inter-quartile ranges] or means ±SD. The median gestational age was 36 [33 - 37] weeks. There was a decrease in fetal PA PI following maternal hyperoxygenation (from 2.47 [2.11 - 2.80] to 2.08 [1.75 - 2.49], p=0.02) with a mean decrease of 21% [9-36] from the baseline. There was an increase in PA AT (43 [40-47] to 57 [47 - 60] ms, p=0.005) leading to an increase in AT:ET (indicating a fall in PVR) following maternal hyperoxygenation (0.25 [0.24 - 0.28] to 0.32 [0.26 - 0.34], p=0.005). There were no changes in the PIs of the UAD or MCA following hyperoxygenation (0.93 to 0.99, p=0.92 and 1.54 to 1.72, p=0.20 respectively). This study demonstrates that maternal hyperoxygenation diminishes the relative vasoconstriction in the fetal pulmonary vasculature. There were no significant changes to the MCA or UAD PI indices following hyperoxygenation suggesting that this effect is unique to the fetal pulmonary vessels.

OP 13 The tryptophan metabolite kynurenine induces vasorelaxation in systemic maternal arteries – A new target for therapeutic intervention?

Introduction The important immunoregulatory role of Kynurenine (Kyn) pathway tryptophan metabolism in the placenta is well established. Activity of this pathway is reduced in pre-eclampsia. Recently Kyn was shown to relax blood vessels and reduce blood pressure in animal models [1] . In a small study of non-pregnant humans (n = 5), Kyn relaxed omental arteries; this was attenuated by Linopirdine (Lin; 10 μM), an inhibitor of type 7 voltage-gated potassium (Kv7) channels [2] . Objectives To determine if Kyn contributes to regulation of vascular tone in systemic resistance arteries in pregnancy. Materials and methods Omental resistance arteries ( Results Treatment with 1, 3 or 6 mM Kyn dose-dependently attenuated arterial constriction to U46619 (N = 4–8, p = 0.003); greatest effect was observed at an intermediate U46619 dose of 10–7 M (change in constriction: control −0.19 ± 0.08 vs Kyn 6 mM −0.61 ± 0.13). Kyn induced relaxation of pre-constricted omental arteries (N = 7, p = 0.032; 0.70 ± 0.11 vs. 0.35 ± 0.08). Treatment with Lin 10 μM had no effect on Kyn-induced relaxation (N = 5, p = ns; 0.22 ± 0.12 vs. 0.17 ± 0.03). Conclusion This is the first study to demonstrate that Kyn has vasorelaxant effects on systemic resistance arteries in pregnancy. This supports our hypothesis that restoring Kyn pathway activity in pre-eclampsia could be a novel therapeutic target to attenuate maternal features of the disease. Kyn-induced relaxation was not inhibited by Lin 10 μM as previously reported outwith pregnancy, suggesting incomplete inhibition of Kv7 channels or an alternate compensatory mechanism.

Spiral artery remodeling and maternal cardiovascular risk: the spiral artery remodeling (SPAR) study.

Women with a history of placental bed disorders, including preeclampsia and intrauterine growth restriction have an increased long-term risk of cardiovascular disease (CVD). Further, similarities exist between atherosclerosis and abnormalities observed in placental bed spiral arteries in pregnancies affected by preeclampsia and intrauterine growth restriction, such as acute atherosis and defective remodeling. This suggests a common pathophysiological pathway underlying both disorders. The aim of this study was to investigate vascular and inflammatory lesions in the placental bed of women with preeclampsia and normal pregnancy using a systematic approach to characterize lesions of the placental bed, and relate spiral artery pathology to postpartum CVD risk assessment. Placental bed punch biopsies were performed following caesarean section and systematically studied to assess vascular pathology, arterial remodeling, and the presence of CD3, CD56, and CD68 cells. In addition, levels of modifiable CVD risk factors were assessed immediately postpartum. We found fewer spiral arteries with complete remodeling in women with preeclampsia than in the control group (21 vs. 68%; P = 0.008). Further, women with preeclampsia showed less presence of CD3 cells in both the decidua and the myometrium. Preliminary findings of CVD risk factor assessment postpartum suggest a correlation between acute atherosis and higher triglyceride and low-density lipoprotein cholesterol levels. Systematic study of vascular pathology in uterine spiral artery biopsy samples in relation to CVD risk factors provides valuable insight into the link between cardiovascular health and placental bed disorders.

Comparison between transdermal nitroglycerin and sildenafil citrate in intrauterine growth restriction: effects on uterine, umbilical and fetal middle cerebral artery pulsatility indices.

To evaluate the effects of transdermal nitroglycerin (GTN) and sildenafil citrate on Doppler velocity waveforms of the uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) arteries in pregnancies with intrauterine growth restriction (IUGR). This was a prospective study of 35 singleton pregnancies (gestational age, 24-31 weeks) with IUGR and abnormal UtA and UA Doppler waveforms. We compared maternal arterial blood pressure and Z-scores of the pulsatility index (PI) of UtA, UA and fetal MCA before and after application of a transdermal GTN patch (average dose, 0.4 mg/h), oral sildenafil citrate (50 mg) or placebo. Statistical analysis was performed by ANOVA for paired samples. There was a significant decrease in UtA-PI after application of GTN (21.0%) and sildenafil citrate (20.4%). A significant reduction in UA-PI was also observed for both GTN (19.1%) and sildenafil citrate (18.2%). There was no difference in UtA- and UA-PI when the GTN and sildenafil groups were compared. No changes in Doppler velocimetry were observed in the placebo group and no significant change in MCA-PI was observed in any group. Maternal arterial blood pressure decreased with administration of both GTN and sildenafil citrate in those with pre-eclampsia. The use of transdermal GTN or sildenafil citrate in pregnancies with IUGR is associated with a significant reduction in both UtA and UA Doppler PI, as well as maternal arterial blood pressure. Neither drug affected the MCA-PI. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Effect of cigarette smoking on vascular flows in pregnancies complicated by intrauterine growth restriction.

Exposure to tobacco smoke during pregnancy may result in intrauterine growth restriction (IUGR). In the study, the effect of tobacco smoke on vascular flows in the middle cerebral artery, umbilical artery, ductus venosus in fetuses and uterine artery in pregnancies complicated by IUGR was investigated. The study subjects were divided into three groups: smoking women with IUGR (n=31), women with idiopathic IUGR (n=28) and healthy controls (n=50). Fetal biometry and flow parameters were measured. Concentration of heavy metals and antioxidants was tested in maternal blood and fetal umbilical cord blood. The Student t test and multiple regression analysis were used. Cotinine and cadmium concentrations were significantly higher in smokers (55.23±54.23, 1.52±0.9), while metallothionein was significantly higher (22.94±8.64) in the idiopathic IUGR group. Strong correlations between cotinine and cadmium concentrations and cerebral-umbilical index were found. Long-term exposure to tobacco smoke deteriorates flows in vital fetal vessels.

DNA methylation contributes to chronic hypoxia‐induced downregulation of large‐conductance Ca2+‐activated K+ channels in uterine arteries in pregnancy (889.3)

Uterine blood flow increases dramatically during pregnancy in part due to an upregulation of the large‐conductance Ca2+‐activated K+ (BKCa) channel in the uterine artery. However, this hemodynamic change is complicated by chronic hypoxia. We hypothesized that DNA methylation may play a role in chronic hypoxia‐induced downregulation of BKCa channels. Uterine arteries were isolated from nonpregnant (NPUA) and near‐term (~140 days) pregnant (PUA) sheep and incubated under 21% or 10.5% O2 for 48 hours at 37°C. Exposure to chronic hypoxia significantly reduced the BKCa current density in PUA (p &lt; 0.05), but not in NPUA. 5‐aza‐2'‐deoxycytidine (5‐aza), a DNA methylation inhibitor, blocked the hypoxia‐mediated effect in PUA. Accordingly, chronic hypoxia decreased a BKCa activator NS 1619‐induced relaxations of PUA, which was abrogated by 5‐aza. Treatment of NPUA ex vivo under 21% O2 with physiological concentrations of estrogen and progesterone (E2β/P4) resulted in increased BKCa current density; and chronic hypoxia suppressed this upregulation. However, 5‐aza reversed the impact of chronic hypoxia and restored the ability of E2β/P4 in upregulating the BKCa current density. Taken together, our findings suggest that an epigenetic modification of DNA methylation plays an important role in chronic hypoxia‐induced downregulation of BKCa channel function in uterine arteries in pregnancy.Grant Funding Source: HL089012, HL110125

Chronic hypoxia‐mediated oxidative stress downregulates the large‐conductance Ca2+‐activated K+ channel activity in uterine arteries in pregnancy (889.4)

Chronic hypoxia during pregnancy constitutes a major insult to maternal cardiovascular homeostasis, leading to complicated uteroplacental circulation. We recently demonstrated that long term high‐altitude hypoxia enhanced uterine arterial myogenic tone, which was mediated by the downregulation of the large‐conductance Ca2+‐activated K+ channel (BKCa) activity via enhanced oxidative stress. In the present study we tested the hypothesis that chronic hypoxia exposure directly increases generation of reactive oxygen species (ROS) in the uterine artery from pregnant sheep, which in turn suppresses BKCa channel activity in VSMCs of the vessel. Uterine arteries were isolated from near‐term (~140 days) pregnant sheep and incubated under 21% or 10.5% O2 for 48 hours at 37 °C. Exposure to chronic hypoxia significantly increased ROS levels and depressed the BKCa current density (p &lt; 0.05). Neither ROS levels nor BKCa current density in tissues cultured in 21% O2 were altered by the antioxidant N‐acetylcysteine (NAC). However, the increased ROS level and depressed BKCa current density during exposure to chronic hypoxia were ablated by NAC. Our findings suggest a direct effect of chronic hypoxia in suppressing the function of BKCa channels in uterine arteries through increased generation of ROS, which may contribute to the increased myogenic tone of uterine arteries in response to chronic hypoxia during gestation.Grant Funding Source: HL089012, HL110125

Gestational hypoxia up-regulates protein kinase C and inhibits calcium-activated potassium channels in ovine uterine arteries.

Objective: The present study tested the hypothesis that gestational hypoxia up-regulates protein kinase C (PKC) and inhibits calcium-activated potassium channels (KCa)-mediated relaxations of uterine arteries in pregnancy. Study design: Uterine arteries were isolated from nonpregnant (NPUA) and pregnant (PUA) (~140 day gestation) sheep maintained at either sea level or high altitude (3,820 m for 110 days, PaO2: 60 mmHg). Contractions of uterine arteries were determined. Key findings: In normoxic PUA, selective inhibition of large-conductance KCa (BK) channels significantly enhanced PKC activator phorbol 12, 13-dibutyrate (PDBu)-induced contractions. This effect was abrogated by chronic hypoxia in gestation. Unlike BK channels, inhibition of small-conductance KCa (SK) channels had no significant effect on PDBu-mediated contractions. In normoxic PUA, activation of both BK with NS1619 or SK with NS309 produced concentration-dependent relaxations, which were not altered by the addition of PDBu. However, in uterine arteries treated with chronic hypoxia (10.5% O2 for 48 h), both NS1619- and NS309-induced relaxations were significantly attenuated by PDBu. In NPUAs, inhibition of BK channels significantly enhanced PDBu-induced contractions in both normoxic and hypoxic animals. Conclusion: The results suggest that in the normoxic condition BK inhibits PKC activity and uterine vascular contractility, which is selectively attenuated by chronic hypoxia during gestation. In addition, hypoxia induces PKC-mediated inhibition of BK and SK activities and relaxations of uterine arteries in pregnancy.