Blood Flow In Preeclampsia Research Articles

Plane-wave ultrasound assessment of ocular blood flow in preeclampsia and correlation with optical coherence tomography angiography

We examined both eyes of 58 post-partum subjects within 72 hours of delivery with plane-wave ultrasound and optical coherence tomography angiography (OCTA). 8 had preeclampsia (PE), 21 severe PE (sPE). 9 chronic or gestational hypertension and 21 were controls. We performed plane-wave ultrasound with a Verasonics Vantage-128 and L22-14vXLF 18 MHz linear array, acquiring 3-angle compound images of the region of the optic nerve and choroid at 6 kHz for 3 s. Data were post-processed to obtain pulsatile flow characteristics of the central retinal artery and vein, the short posterior ciliary arteries and the choroid. Ultrasound revealed significantly elevated blood flow velocity and reduced resistance in sPE compared to controls. Spectral domain OCTA images were acquired with a Zeiss Plex Elite immediately before or after ultrasound. We analyzed 6x6 images centered on the macula and optic nerve to determine vascular density of the superficial and deep retina, and 3 i 3 images centered on the macula to determine foveal avascular zone area and vascular density of the choriocapillaris. Comparison of ultrasound with OCTA findings revealed significant correlations between flow velocity and resistance with vascular density in the superficial retina and choriocapillaris. These findings demonstrate a relationship between functional (ultrasound flow) and structural (OCTA vascular density) parameters in the eye, and especially in the choriocapillaris which we hypothesized would play role in the reduced flow resistance observed in sPE.

Mechanotransduction and Uterine Blood Flow in Preeclampsia: The Role of Mechanosensing Piezo 1 Ion Channels.

There is a large increase in uterine arterial blood flow during normal pregnancy. Structural and cellular adjustments occur in the uterine vasculature during pregnancy to accommodate this increased blood flow through a complex adaptive process that is dependent on multiple coordinated and interactive influences and this process is known as "vascular remodeling." The etiology of preeclampsia involves aberrant placentation and vascular remodeling leading to reduced uteroplacental perfusion. The placental ischemia leads to development of hypertension and proteinuria in the mother, intrauterine growth restriction, and perinatal death in the fetus. However, the underlying source of the deficient vascular remodeling and the subsequent development of preeclampsia remain to be fully understood. Mechanoreceptors in the vascular system convert mechanical force (shear stress) to biochemical signals and feedback mechanisms. This review focuses on the Piezo 1 channel, a mechanosensitive channel that is sensitive to shear stress in the endothelium; it induces Ca2+ entry which is linked to endothelial nitric oxide synthase (eNOS) activation as the mechanoreceptor responsible for uterine vascular dilatation during pregnancy. Here we describe the downstream signaling pathways involved in this process and the possibility of a deficiency in expression of Piezo 1 in preeclampsia leading to the abnormal vascular dysfunction responsible for the pathophysiology of the disease. The Piezo 1 ion channel is expressed in the endothelium and vascular smooth muscle cells (VSMCs) of small-diameter arteries. It plays a role in the structural remodeling of arteries and is involved in mechanotransduction of hemodynamic shear stress by endothelial cells (ECs).

Radicals, Oxidative/Nitrosative Stress and Preeclampsia.

Preeclampsia (PE) has a profound effect in increasing both maternal and fetal morbidity and mortality especially in third World. Disturbances of extravillous trophoblast migration toward uterine spiral arteries is characteristic feature of PE, which, in turn, leads to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Underlying pathogenesis appeared to be an altered bioavailability of nitric oxide (NO•) and tissue damage caused by increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The increase in ROS and RNS production or the decrease in antioxidant mechanisms generates a condition called oxidative and nitrosative stress, respectively, defined as the imbalance between pro- and antioxidants in favor of the oxidants. Additionally, ROS might trigger platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. As a consequence of these disorders could result in deficiencies in oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the one hand, enzymatic and nonenzymatic antioxidants scavenge ROS and protect tissues against oxidative damage. More specifically, placental antioxidant enzymes including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) protect the vasculature from ROS, maintaining the vascular function. On the other hand, ischemia in placenta in PE reduces the antioxidant activity. Collectively, the extent of oxidative stress would increase and therefore leads to the development of the pathological findings of PE including hypertension and proteinuria. Our goal in this article is to review current literature about researches demonstrating the interplay between oxidative, nitrosative stresses and PE, about their roles in the pathophysiology of PE and also about the outcomes of current clinical trials aiming to prevent PE with antioxidant supplementation.

Relationship between insulin resistance and tissue blood flow in preeclampsia.

Preeclampsia is characterized by generalized endothelial dysfunction and impaired maternal tissue perfusion, and insulin resistance is a prominent feature of this disease. The aim of this study was to test the hypothesis that insulin resistance in preeclampsia is related to the reduced resting tissue blood flow. We used venous occlusion plethysmography to compare the resting calf muscle blood flow (measured as QaU) in 20 nulliparous women with preeclampsia and 20 normal pregnant controls matched for maternal age, gestational age, parity and BMI during the third trimester. Fasting blood samples were obtained to measure the plasma concentrations of insulin and glucose, and to calculate the fasting insulin resistance index (FIRI), a measure of insulin resistance in both groups of women. Calf blood flow was significantly reduced in the preeclampsia group (1.93 ± 0.86 QaU), compared with normal pregnant controls (3.94 ± 1.1 QaU, P < 0.001). Fasting insulin concentrations and Insulin Resistance Index were significantly higher in preeclampsia compared with normal pregnancy (P < 0.001 for both variables). There were significant inverse correlations between resting calf blood flow and fasting insulin concentrations (r = -0.57, P = 0.008) and FIRI (r = -0.59, P = 0.006) in preeclampsia, but not in normal pregnancy. These findings support our hypothesis and raise the possibility that reduced tissue blood flow may a play a role in the increased insulin resistance seen in preeclampsia.

Nitric oxide and reactive oxygen species in the pathogenesis of preeclampsia.

Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue damage caused by increased levels of reactive oxygen species (ROS). Furthermore, superoxide (O2−) rapidly inactivates NO and forms peroxynitrite (ONOO−). It is known that ONOO− accumulates in the placental tissues and injures the placental function in PE. In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. The disorders could lead to the reduction of oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the other hand, several antioxidants scavenge ROS and protect tissues against oxidative damage. Placental antioxidants including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) protect the vasculature from ROS and maintain the vascular function. However, placental ischemia in PE decreases the antioxidant activity resulting in further elevated oxidative stress, which leads to the appearance of the pathological conditions of PE including hypertension and proteinuria. Oxidative stress is defined as an imbalance between ROS and antioxidant activity. This review provides new insights about roles of oxidative stress in the pathophysiology of PE.

Maternal tissue blood flow and oxygen saturation in pre-eclampsia and intrauterine growth restriction

ObjectiveTo investigate the hypothesis that impaired maternal tissue perfusion occurs in pre-eclampsia and intrauterine growth restriction (IUGR) and this correlates with maternal tissue oxygenation. Study designStrain gauge plethysmography was used to compare maternal calf blood flow during the third trimester in 16 women with pre-eclampsia, 6 women with IUGR and 16 normal pregnant controls. A Mediaid iPOX pulse oximeter was used to measure maternal tissue oxygenation in the three groups and these were compared with tissue blood flow. ResultsMaternal tissue blood flow was significantly reduced in pre-eclampsia compared to the two other groups (p=0.003). Blood flow was significantly reduced in pre-eclampsia compared to IUGR (p=0.03). However there was no difference in blood flow between normal pregnancy and IUGR groups (p=0.76). No significant difference was noted in maternal tissue oxygenation between the normal pregnancy, pre-eclampsia and IUGR groups (mean±S.E.M. [97.13±0.4, 96.69±0.33, 97.83±0.47 respectively], p=0.26). No correlation was noted between blood flow and tissue oxygenation in the three groups of women. ConclusionWe have demonstrated that reduced maternal resting tissue blood flow present in women with pre-eclampsia is not seen in women with IUGR and the reduction in blood flow in pre-eclampsia is not associated with changes in maternal tissue oxygenation.

PM.18 Maternal Resting Peripheral Blood Flow and Tissue Oxygenation in Pregnancies Complicated with Pre-Eclampsia and IUGR

BackgroundPre-eclampsia is characterised by hypertension and proteinuria and associated with systemic hypoperfusion of multiple maternal organs. Intrauterine growth restriction (IUGR) is a recognised complication of pre-eclampsia and the two conditions...

Abstract P090: The Contractile Effect of Angiotensin II Type 1 Receptor Autoantibodies on Human Placental Vessels

Background: Decreased placental perfusion induced by abnormal placental vascular contraction is one of the pathological basis of preeclampsia. It has been reported that the sera titers of the autoantibody against the second extracellular loop of angiotensin II type 1 receptor (AT1-AA) were negatively correlated with placental blood flow in preeclampsia. Our previous study has found that AT1-AA could induce contraction of rat thoracic aorta and coronary rings by activing angiotensin II type 1 receptor (AT1R). However, there is no direct evidence for explaining whether AT1-AA might cause vasoconstriction on human placental blood vessels. Methods: The SD rats were immunized with the synthetic peptide corresponding to the sequence of the second extracellular loop of the human AT1 receptor (AT1R-EC II ), and anti-AT1R antibody (AT1R-Ab) was extracted. The expression of AT1R on human placental vessels was determined by immunohistochemistry. The effects of AT1R-Ab on placental vessels were measured with isolated vascular ring technique. Results: (1) AT1R was highly expressed in the human placental artery, vein and vascular endothelial cells. (2) AT1R-Ab (10 mmol/L) respectively enhanced the contraction of the placental arteries and veins (29.21% ± 3.7% vs . 21.35% ± 2.8%, P &gt;0.05), which could be completely reversed when AT1R was blocked by AT1R inhibitor. (3) AT1R-Ab (0.1, 1 and 10 mmol/L) induced placental vasoconstriction of normal human. The percentage of maximal contraction was 2.73% ± 1.11%, 4.00% ± 3.2% and 33.30% ± 5.6%, respectively. There was significantly difference between the three groups for contraction amplitude induced by different concentrations of AT1R-Ab ( P &lt;0.01). (4) AT1R-Ab (0.1, 1 and 10 mmol/L) induced placental vasoconstriction of preeclampsia. The percentage of maximal contraction was 1.74% ± 0.3%, 5.58% ± 1.41% and 3.73% ± 2.5%, respectively. There was significantly difference between the three groups for contraction amplitude induced by different concentrations of AT1R-Ab ( P &lt;0.01). Conclusion: AT1R-Ab could induce human placental vasoconstriction in a concentration-dependent manner, which suggested that AT1-AA might be involved in the pathogenesis of preeclampsia by directly contracted placental blood vessles.

Increased Cerebral Blood Flow in Preeclampsia With Magnetic Resonance Imaging

Increased Cerebral Blood Flow in Preeclampsia With Magnetic Resonance Imaging

The effect of magnesium sulfate on large cerebral artery blood flow in preeclampsia

Objectives. To determine the effect of a 6 gram intravenous bolus of magnesium sulfate on maternal cerebral blood flow in women with preeclampsia.Study Desiqn. Velocity-encoded phase-contrast magnetic resonance imaging studies were performed on twelve preeclamptic women prior to and immediately after infusion of a 6 gram magnesium sulfate loading dose. Cerebral blood flow was determined at the bilateral proximal middle and posterior cerebral arteries. Study participants returned 6 weeks postpartum for a non-pregnant measurement of cerebral blood flow. The Wilcoxon paired-sample test was used with statistical significance defined as p<0.05.Results. There was no significant difference in cerebral vessel diameter nor blood flow for any of the examined arteries between the pre- and post magnesium sulfate therapy states.Conclusions. The absence of a significant difference in cerebral blood flow of the middle and posterior cerebral arteries before and after infusion of a 6 gram loading dose of magnesium sulfate in women with preeclampsia could suggest the absence of vasoconstriction of the large cerebral arteries in preeclampsia and question the role of magnesium sulfate as a vasodilator of these arteries.

Increased cerebral blood flow in preeclampsia with magnetic resonance imaging

The purpose of this study was to compare third trimester and nonpregnant cerebral blood flow of women with preeclampsia to normotensive control subjects with the use of magnetic resonance imaging techniques. Nine normotensive pregnant women and 12 untreated women with preeclampsia underwent velocity-encoded phase contrast magnetic resonance imaging of the bilateral middle and posterior cerebral arteries in the third trimester and at 6 to 8 weeks after delivery. The Student t test was used for comparison, with a probability value of <.05 considered significant. Third-trimester large cerebral artery blood flow was significantly higher in preeclampsia. Mean vessel diameter was unchanged, except for the left posterior cerebral artery. There was no difference in mean vessel diameter or cerebral blood flow between the 2 groups while the women were not pregnant. Cerebral blood flow is increased significantly in preeclampsia. We hypothesize that increased cerebral blood flow ultimately could lead to eclampsia through hyperperfusion and the development of vasogenic edema.

Impaired retrograde transmission of vasodilatory signals via the endothelium in pre-eclampsia: a cause of reduced tissue blood flow?

There is evidence that tissue blood flow is regulated by retrograde transmission of signals initiated at capillary and post-capillary sites, and transmitted via the endothelium to modulate pre-capillary resistance. We have used pre-eclampsia as a model to test the hypothesis that normal endothelium is required to enable adjustment of blood flow to match tissue requirements. Integrity of the endothelial pathway was assessed by measuring calf blood flow at increasing venous pressures, using an established small cumulative-step venous-congestion plethysmography protocol in ten women with pre-eclampsia, 17 normal pregnant controls and ten non-pregnant women. Endothelial cell activation was assessed by measuring plasma levels of the cell adhesion molecules, intercellular cell-adhesion molecule-1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1) and E-selectin. Baseline calf blood flow was significantly lower in pre-eclampsia than in the other two groups (P<0.0001; ANOVA). In the pre-eclampsia group, there was a fall in blood flow as venous congestion pressure was raised (P<0.0001; ANOVA). No such change was observed in the other two groups. A significant inverse correlation was observed between the reduction in blood flow in pre-eclampsia and the levels of E-selectin (r=-0.92, P=0.0002), VCAM-1 (r=-0.93, P=0.0008) and ICAM-1 (r=-0.86, P=0.001). The differences between the pre-eclamptic women and the other two groups support the notion that the failure to sustain blood flow during a cumulative pressure step protocol in the pre-eclamptic group might be influenced by interference with the retrograde transmission of signals via the endothelium in these patients.

Forearm blood flow in pre-eclampsia

Objective 1. To characterise the forearm vascular reactivity of women with pre-eclampsia in the third trimester of pregnancy and compare it with that in normal or gestational hypertensive pregnancies. 2. To document female sex steroid (oestradiol, progesterone, oestriol and βhCG) levels in the three groups of women. Design Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial infusion of saline and vasoactive substances: angiotensin II, sodium nitroprusside, acetylcholine and N G-monomethyl- l-arginine ( l-NMMA). Setting Research laboratory at St George Hospital, Kogarah, Sydney, Australia. Sample Fifteen non-pregnant women in the follicular phase of the menstrual cycle, 15 third trimester normal pregnant women, 13 women in the third trimester with gestational hypertension and 15 women with pre-eclampsia. Main outcome measures Changes in forearm blood flow in response to vasoactive substances. Results Normal pregnant women had higher baseline forearm blood flow than non-pregnant women, decreased vasodilator responses to sodium nitroprusside and reduced vasoconstrictor responses to angiotensin II. No difference in response to angiotensin II, sodium nitroprusside or l-NMMA was found among normal pregnant, pre-eclampsia or gestational hypertension women, but vasodilatory responses of pre-eclamptic women to acetylcholine were reduced compared with normal pregnant women. Higher serum progesterone levels were found in women with pre-eclampsia and gestational hypertension than in normal pregnancy. Conclusion The hyperdynamic circulation of normal pregnancy is characterised by refractoriness to angiotensin II but this is not altered in pre-eclampsia. Pre-eclamptic women demonstrate a reduced vasodilator response to acetylcholine which, in the absence of any alteration in response to l-NMMA, implies that factors other than nitric oxide deficiency mediate the vasoconstriction of pre-eclampsia.

Effect of hyperventilation on cerebral blood flow velocity in preeclamptic pregnancies: is there evidence for an altered cerebral vasoreactivity?

The purpose of this study was to investigate cerebral arteriolar vasoreactivity function in preeclampsia. Preeclamptic (n = 26) and healthy pregnant (n = 22) women underwent transcranial Doppler sonography of the middle cerebral artery at rest and after 60 seconds of hyperventilation (HV). Systolic, diastolic, and mean blood flow velocities were recorded. The percentage change of the blood flow velocities after HV was calculated. Mean blood flow velocity of the middle cerebral artery was higher in preeclamptic women as compared with healthy pregnant women. No difference could be detected in percentage change of middle cerebral artery blood flow velocities after HV between the two groups. There is no evidence of a small-vessel vasoconstriction among preeclamptic patients. The role of vasoconstriction of the large cerebral arteries and vasodilation of the resistance arterioles, as well as a combination of these 2 pathomechanisms, in determining cerebral blood flow in preeclampsia and eclampsia should be investigated in further studies.

Resting peripheral blood flow in normal pregnancy and in pre-eclampsia

Multiple organ dysfunction followed by end organ failure occurs in pre-eclampsia. While one would intuitively reason that one of the factors contributing to the end organ failure is poor nutritional blood flow, this has yet to be demonstrated. The aim of the present study was to determine whether changes in resting nutritional blood flow occur in pre-eclampsia. We used strain-gauge plethysmography to study calf blood flow in 19 women with pre-eclampsia, 13 normal pregnant women and 17 non-pregnant controls. We reasoned that, since the calf comprises mostly skeletal muscle, without anastomotic channels, blood flowing through this region would primarily reflect nutritive flow. Calf blood flow was significantly reduced in women with pre-eclampsia (1.95+/-0.9 ml.min(-1).100 ml(-1)) compared with normal pregnant (3.9+/-1.4 ml.min(-1).100 ml(-1)) and non-pregnant (3.8+/-1.0 ml.min(-1).100 ml(-1)) women (P=0.0004 and P=0.0005 respectively; ANOVA). Blood flow in pre-eclampsia was also correlated significantly with platelet count as an index of disease severity. In addition, there was a significant negative correlation between blood flow and systolic blood pressure (r=-0.69, P=0.004) in the women with pre-eclampsia. These findings support the hypothesis that nutritional blood flow is reduced in pre-eclampsia. We suggest that measurement of resting calf blood flow could give a non-invasive index of deterioration of nutritive blood flow to vital organs in pre-eclampsia.

The effects of transdermal nitroglycerin (nitrol patch) on the uterine and umbilical artery blood flow in preeclampsia: a randomized double blind placebo controlled study

The effects of transdermal nitroglycerin (nitrol patch) on the uterine and umbilical artery blood flow in preeclampsia: a randomized double blind placebo controlled study

Reactivities to serotonin and histamine in umbilical and placental vessels during the third trimester after normotensive pregnancies and pregnancies complicated by preeclampsia

Objective: The aim of the study was to evaluate responses of umbilical and placental arteries and veins to serotonin and histamine after normotensive pregnancies and pregnancies complicated by preeclampsia. Study Design: Each pair of placentas from a normotensive woman and a woman with preeclampsia was matched for gestational age. Rings of these vessels were prepared and mounted in tissue baths under their respective optimal passive tension. Cumulative concentration-response curves to serotonin and histamine were measured. Results: Responses to serotonin were decreased in umbilical vessels from the preeclampsia group with respect to the normotensive group. This is reflected by reduced maximum responses and sensitivity (negative logarithm of the 50% effective concentration) to serotonin. Maximum response to serotonin was significantly decreased in placental vein rings from the preeclampsia group. We recorded a decreased maximal response to histamine in placental vein rings from pregnancies complicated by preeclampsia with respect to those from normal pregnancies. Among normotensive women there was a significant positive linear relationship between neonatal weight and sensitivity to serotonin in umbilical and placental veins. This relationship was totally absent in preeclampsia. Sensitivity to histamine was linearly related to neonatal weight in umbilical vessels of the pooled results of both experimental groups. Conclusion: The vasoconstrictive effects of serotonin, but not those of histamine, are decreased in umbilical and placental vessels after preeclampsia. Sensitivities to serotonin and histamine change in umbilicoplacental vessels during the third trimester. Altered reactivity to serotonin may play a significant role in the reduction of umbilicoplacental blood flow in preeclampsia. (Am J Obstet Gynecol 1999;180:650-9.)

Altered expression of gelatinase and surface-associated plasminogen activator activity by trophoblast cells isolated from placentas of preeclamptic patients

OBJECTIVE: This study compared in vitro degradative properties of trophoblasts isolated from placentas of preeclamptic patients with those of trophoblasts isolated from placentas of patients with uncomplicated pregnancies. Specifically, the expression of gelatinases, plasminogen activators, and plasminogen activator inhibitor type 1 by these cells was examined. STUDY DESIGN: Gelatinase and plasminogen activator secretion were determined by zymography, whereas antigenic levels of urinary-type plasminogen activator and plasminogen activator inhibitor type 1 in culture-conditioned medium were determined by enzyme-linked immunosorbent assay. We also evaluated expression of cell-surface plasminogen activator activity with a sensitive assay that uses the fluorescent plasmin substrate H-D-Val-Leu-Lys-7-amino-4-methylcoumarin. RESULTS: Cells from both normal and preeclamptic placentas secreted variable levels of gelatinase, of which the most predominant was matrix metalloproteinase-9 (gelatinase B). In 60% of the media conditioned by preeclamptic cells the matrix metalloproteinase-9 present was exclusively of a higher molecular weight (>92 kd) than the predominant enzyme secreted by trophoblasts isolated from normal placentas. Incubation of the preeclamptic cell culture-conditioned media with p-aminophenylmercuric acetate, an activator of metalloproteinases, resulted in a decrease in the apparent molecular weight of the enzyme, indicating that most of the matrix metalloproteinase-9 contained in these samples was in the inactive form. Although trophoblasts from normal and preeclamptic placentas secreted similar amounts of urinary-type plasminogen activator and plasminogen activator inhibitor type 1, the latter cells expressed significantly less (p < 0.001) cell surface plasminogen activator activity. CONCLUSION: These results suggest that abnormal uteroplacental blood flow in preeclampsia (as a result of either shallow invasiveness of the uterine arteries or excessive fibrin deposition within the intervillous spaces) might result from altered expression of active proteinases by trophoblasts. (Am J Obstet Gynecol 1996;175:555-62.)

Enhancement of hepatic artery resistance to blood flow in preeclampsia in presence or absence of HELLP syndrome (hemolyis, elevated liver enzymes, and low platelets)

Our purpose was to test the hypothesis that the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome is the result of excessive vasoconstriction of the hepatic arterial circulation. Doppler ultrasonography was used to measure the pulsatility index of the common hepatic artery in 14 women with preeclampsia, 15 with preeclampsia complicated by HELLP syndrome, and 8 with HELLP syndrome but without proteinuria. Gestational age ranged from 24 to 38 weeks. The study group was compared with a reference group (n = 42). Both in preeclampsia and in the HELLP syndrome the hepatic artery pulsatility index values were significantly increased compared with the reference group. However, no significant differences were found between the preeclamptic group, the HELLP group with proteinuria, and those with HELLP without proteinuria. These findings indicate that hepatic artery resistance to blood flow is increased in preeclampsia in the presence or absence of the HELLP syndrome. The results also demonstrate that vasoconstriction of the hepatic arteries is not more pronounced in the HELLP syndrome than in other manifestations of preeclampsia. Therefore factors other than vasoconstriction are likely to be responsible for the development of the HELLP syndrome.

Effects of isradipine on endothelin-induced constriction of myometrial arteries in normotensive pregnant women.

The results of our previous studies suggested that endothelin-1 (ET-1) might be contributory to the impaired uteroplacental blood flow seen in preeclampsia. The aim of this study was to investigate the in vitro influence of isradipine on ET-1-induced contraction of myometrial resistance arteries from pregnant women, as these vessels are partly responsible for the regulation of uteroplacental blood flow in preeclampsia. Small myometrial arteries were dissected from myometrium obtained from 20 normotensive term pregnant women undergoing elective cesarean section and mounted in a tissue chamber. Tension was recorded isometrically. When ET-1 (10(-8) mol/L)-contracted vessels were exposed to increasing concentrations (10(-6), 10(-5), and 10(-4) mol/L) of isradipine, the myometrial arteries demonstrated essentially no relaxation. A significant mean relaxation of 31% was seen only with the highest isradipine concentration of 10(-3) mol/L. Pretreatment with isradipine attenuated ET-1-induced contraction by 26% at 3 x 10(-4) mol/L and by up to 80% at 10(-3) mol/L. Preincubation with lower concentrations of isradipine did not significantly reduce subsequent ET-1 contraction. The present study has thus shown that isradipine at high concentrations counteracts ET-1-induced constriction of myometrial arteries in term pregnant women. Pretreatment with isradipine at high concentrations attenuates the ET-1 contraction.