atrial-natriuretic-factor and Pre-Eclampsia

Corin is a transmembrane protease that activates atrial natriuretic peptide (ANP), an important hormone in regulating salt-water balance and blood pressure. This review focuses on the regulation of corin function and potential roles of corin defects in hypertensive, heart, and renal diseases.. Proprotein convertase subtilisin/kexin-6 has been identified as a primary enzyme that converts zymogen corin to an active protease. Genetic variants that impair corin intracellular trafficking, cell surface expression, and zymogen activation have been found in patients with hypertension, cardiac hypertrophy, and pre-eclampsia. Reduced corin expression has been detected in animal models of cardiomyopathies and in human failing hearts. Low levels of circulating soluble corin have been reported in patients with heart disease and stroke. Corin, ANP and natriuretic peptide receptor-A mRNAs, and proteins have been colocalized in human renal segments, suggesting a corin-ANP autocrine function in the kidney.. Corin is a key enzyme in the natriuretic peptide system. The latest findings indicate that corin-mediated ANP production may act in a tissue-specific manner to regulate cardiovascular and renal function. Corin defects may contribute to major diseases such as hypertension, heart failure, pre-eclampsia, and kidney disease.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Diseases; Humans; Hypertension; Kidney; Kidney Diseases; Pre-Eclampsia; Pregnancy; Proprotein Convertases; Receptors, Atrial Natriuretic Factor; Serine Endopeptidases

In pregnancy, uterine spiral artery remodeling is an adaptive morphological change at the maternal and fetal interface, which is critical for dilating the artery and promoting blood flow to the fetus. Incompletely remodeled spiral arteries have been recognized as a common pathological feature in preeclamptic patients. To date, the molecular mechanism that controls spiral artery remodeling is not well defined. Corin is a transmembrane serine protease discovered in the heart, where it converts pro-atrial natriuretic peptide (pro-ANP) to active ANP, a cardiac hormone that regulates salt-water balance and blood pressure. Recent studies show that corin is up-regulated in the decidua of the pregnant uterus, suggesting a potential role of corin in pregnancy. In mice lacking corin or ANP, high blood pressure and proteinuria were found at late gestational stages. Histological analysis indicated delayed trophoblast invasion and impaired spiral artery remodeling in the uterus. In humans, CORIN gene mutations were identified in patients with preeclampsia. In this review, we discuss the function of corin and ANP in regulating blood pressure and their potential role in preeclampsia.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Female; Gene Expression; Humans; Mice; Mice, Knockout; Mutation; Pre-Eclampsia; Pregnancy; Serine Endopeptidases; Uterine Artery; Uterus

In the last three decades many members of the natriuretic peptide family was isolated. The function and physiological role of these peptides are pleiotropic. All natriuretic peptides are synthesized from polypeptide precursors. Together with the sympathetic nervous system and other hormones they play key roles, like an endogenous system in the regulation of the body fluid homeostasis and blood pressure. Changes in this balance lead to dysfunction in the endothel and left ventricle, which can cause severe complications. In many cardiovascular diseases natriuretic peptides serve not only as marker for diagnosis and prognosis but they have therapeutic importance. In the last years the potential use of the elevated BNP levels for diagnosis of pre-eclampsia was examined. In our review we discuss the current understanding of molecular biology, biochemistry and clinical relevance of natriuretic peptides.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Diseases; Female; Humans; Liver Cirrhosis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Pre-Eclampsia; Pregnancy; Renal Insufficiency; Shock, Septic; Tissue Distribution

Preeclampsia is a multisystem disorder peculiar to human pregnancy. It occurs in 4-5% of all pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity. The pathophysiology of this syndrome is not fully understood. Two stages of vascular dysfunction seem to be involved. In the early stage suboptimal development of the placenta and a hemodynamic maladaptation to pregnancy exist. At this stage maternal constitutional factors such as genetic and immunological factors and pre-existing vascular diseases may play a role. Due to this defective placentation a factor is released from the placenta, supposedly under the influence of ischemia. This factor then results in the late vascular dysfunction characterised mainly by a generalised endothelial dysfunction, leading to the clinical syndrome of preeclampsia. This review attempts to unravel the mechanisms that may contribute to preeclampsia-associated changes in vascular function and to indicate the research needed to improve our understanding of this disease.

Topics: Adult; Arteries; Atrial Natriuretic Factor; Endothelial Growth Factors; Endothelium, Vascular; Epoprostenol; Female; Genotype; Humans; Lymphokines; Muscle, Smooth, Vascular; Placenta; Pre-Eclampsia; Pregnancy; Thromboxane A2; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vasoconstriction

Our goals were (1) to use meta-analysis to determine whether pregnancy and the puerperium are accompanied by alterations in plasma atrial natriuretic peptide levels when compared with the nonpregnant state and (2) to evaluate the additional effects of hypertensive disease during pregnancy on plasma atrial natriuretic peptide levels.. Articles measuring atrial natriuretic peptide levels during pregnancy were reviewed. Data from articles meeting inclusion criteria were abstracted, and a meta-analysis was performed with the use of the maximum likelihood methods of Jennrich and Schluchter (Biometrics 1986;42:805-20).. The mean atrial natriuretic peptide level in nonpregnant control subjects was 28.7 pg/ml (95% confidence interval 22.5 to 36.7). The mean plasma atrial natriuretic peptide level rose 41% to 40.5 pg/ml (95% confidence interval 31.7 to 51.8) in the third trimester (p < 0.0001). It was 71.1 pg/ml (95% confidence interval 51.2 to 98.7) or 148% greater than the mean nonpregnant level during the first week post partum (p < 0.0001). Compared with levels in pregnant control subjects, plasma atrial natriuretic peptide levels increased 52% to 52.1 pg/ml (95% confidence interval 32.9 to 82.5) in women with gestational hypertension (p < 0.005) and 130% to 78.8 pg/ml (95% confidence interval 52.3 to 118.8) in women with preeclampsia (p < 0.0001). Chronic hypertension did not significantly alter atrial natriuretic peptide levels.. The 41% increase in atrial natriuretic peptide levels in the third trimester suggests that atrial stretch receptors sense the expanded blood volume as normal to moderately increased. The rise in atrial natriuretic peptide during the first week post partum is consistent with known hemodynamic changes and suggests that atrial natriuretic peptide may be involved in the postpartum diuresis. The marked increase in plasma atrial natriuretic peptide levels observed in preeclampsia is not likely to result from elevated arterial pressures alone but may reflect underlying factors unique to this disease process.

Topics: Atrial Natriuretic Factor; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Reference Values

Topics: Atrial Natriuretic Factor; Blood Volume; Female; Humans; Models, Cardiovascular; Pre-Eclampsia; Pregnancy; Renin-Angiotensin System

Topics: Animals; Atrial Natriuretic Factor; Eicosanoids; Female; Hemodynamics; Humans; Hypertension; Kidney; Maternal-Fetal Exchange; Pre-Eclampsia; Pregnancy; Pregnancy, Animal

Atrial natriuretic peptide (ANP) is a potent natriuretic and hypotensive substance whose importance in pregnancy has not been fully elucidated. Because abnormalities of sodium and water balance are known to be involved in the pathogenesis of toxemic pregnancy, the authors attempted to evaluate the role of ANP by measuring its plasma concentration in 16 normal and 22 toxemic pregnant women (gestational age 26-40 wks, mean 34.5 +/- 1.2 and 28-40 wks, mean 36.0 +/- 1.0, respectively). The weight gain during pregnancy was significantly higher in the toxemic group (13.9 +/- 1.0 vs 9.1 +/- 1.0 kg, p less than 0.01). Plasma ANP level in the toxemic group (40.65 +/- 6.17 pg/ml) was significantly (p less than 0.05) increased compared to that measured in the normal pregnancy group (22.46 +/- 4.22 pg/ml). There was no statistical correlation between ANP levels and gestational age or weight gain during pregnancy. The results suggest that ANP may play a role in the regulation of impaired water and sodium homeostasis in toxemic pregnancy.

Topics: Atrial Natriuretic Factor; Female; Humans; Pre-Eclampsia; Pregnancy

Recent studies suggest that drugs affecting prostacyclin and thromboxane production may be able to affect the development of preeclampsia. In order to use these agents effectively, we must be able to select properly women at high risk. This review evaluates a number of historic and physical factors and laboratory tests that may aid in the prediction of preeclampsia. Family history, parity, and the roll-over test are currently the most efficient methods that are widely available. Two relatively new laboratory tests, plasma fibronectin concentration and urinary calcium/creatinine ratio, hold the greatest promise for the near future.

Topics: Angiotensin II; Antithrombin III; Atrial Natriuretic Factor; beta-Thromboglobulin; Blood Pressure; Blood Proteins; Calcium; Cardenolides; Digoxin; Female; Humans; Iron; Pre-Eclampsia; Pregnancy; Saponins; Serum Albumin; Uric Acid

Topics: Animals; Atrial Natriuretic Factor; Female; Humans; Pre-Eclampsia; Pregnancy; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

Preeclampsia is a unique disease of pregnancy. Delivery via caesarean section is the most important way of terminating the pregnancy and treating preeclampsia. Perioperative fluid therapy is performed to maintain the circulatory volume and reduce tissue edema. This study evaluated the effects of hypertonic sodium chloride hydroxyethyl starch 40 (HSH40) as perioperative fluid therapy for preeclampsia patients.. Forty preeclamptic women were randomly divided into two groups: the Ringer's solution group and the HSH40 group. Their ECG, HR, MAP, and SPO2 were monitored. Their MVP and HR were recorded at five, eight, and ten minutes after anesthesia induction and at the end of the caesarean section. The corresponding volume of infusion, blood loss, and urine output during the operation were also recorded. Venous samples were collected before HSH40 infusion and 30 min after infusion to measure the plasma concentrations of ET, TXB2, 6-keto-PGF1α, and ANP via a radioimmunoassay.. HSH40 infusion significantly decreased the plasma ET levels (p < 0.01), significantly changed the plasma ANP and TXB2 levels (p < 0.05), and significantly increased the plasma 6-keto-PGF1α levels (p < 0.01) in the experimental group compared with those before infusion. The plasma levels of ET, ANP, TXB2, and 6-keto-PGF1α did not significantly change in the control group. Compared with T1, MAP decreased significantly at T2, T3, T4, and T5 within groups (p < 0.05) and between the two groups. MAP significantly changed at T2, T3, T4, and T5 (p < 0.05). HR did not significant change at T1, T2, T3, T4, and T5 within or between groups. Volume of infusion and urine volume significantly differed between groups (p < 0.05).. Low-dose HSH40 lowers the plasma levels of vasoconstrictor substances (ET and TXB2) and increases the levels of vasodilator substances (6-keto-PGF1α and ANP) during preeclampsia. It effectively maintains and stabilizes the circulating blood volume, increasing renal blood flow, which improves renal function and increases urine output.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Atrial Natriuretic Factor; Cesarean Section; Female; Fluid Therapy; Humans; Hydroxyethyl Starch Derivatives; Isotonic Solutions; Perioperative Care; Plasma Substitutes; Pre-Eclampsia; Pregnancy; Ringer's Solution; Saline Solution, Hypertonic; Therapeutics; Thromboxane B2

Atrial natriuretic factor (ANF), produced by cytotrophoblast cells of the human placenta, may be involved in the regulation of uteroplacental blood flow. Pre-eclampsia is associated with maternal hypertension and reduced uteroplacental perfusion. The relationship between pre-eclampsia and placental production of ANF is not known. This study measured pro-ANF mRNA levels by Northern blot analysis in placentae delivered by caesarean section at preterm and term gestations from women with normotensive and pre-eclamptic pregnancies and found no significant difference between pre-eclampsia and normal pregnancy at either gestation. This result suggests that placental production of ANF is not altered at the pretranslational level during pre-eclampsia.

Topics: Adult; Atrial Natriuretic Factor; Base Sequence; Blotting, Northern; Cesarean Section; Female; Gestational Age; Humans; Molecular Sequence Data; Placenta; Polymerase Chain Reaction; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Probability; Protein Precursors; Reference Values; RNA, Messenger; Sensitivity and Specificity; Statistics, Nonparametric

Preeclampsia is a gestational disease characterized by two major pathological changes-shallow trophoblast invasion and impaired spiral artery remodeling. Atrial natriuretic peptide (ANP) is a kind of peptide hormone that regulates blood pressure, while the lack of active ANP participates in preeclampsia pathogenesis. However, the underlying mechanism of how ANP modulates trophoblasts function remains unclarified. Here, we performed isobaric tags for relative and absolute quantification (iTRAQ) in ANP-treated HTR-8/SVneo cells and identified Protein Kinase 3 (PKN3) as the downstream factor of ANP, which was downregulated in preeclamptic placenta. Chromatin immunoprecipitation analysis and luciferase assays showed that NFYA was one of the transcription factors for the PKN3 promoter, which was also regulated by ANP treatment in HTR-8/SVneo cells. Transmission electron microscopy and Western Blotting in HTR-8/SVneo cells indicated that ANP inhibited autophagy via AMPK-mTORC1 signaling, while excess autophagy was observed in preeclamptic placenta. The increased expression of PKN3 and enhanced cell invasion ability in HTR-8/SVneo cells induced by ANP could be abolished by autophagy activation or transfection with PKN3 shRNA or NFYA shRNA or NPR-A shRNA via regulating the invasion-related genes and the epithelial mesenchymal transition molecules. Our results demonstrated that ANP could enhance trophoblast invasion by upregulating PKN3 via NFYA promotion through autophagy inhibition in an AMPK/mTORC1 signaling-dependent manner.

Topics: AMP-Activated Protein Kinases; Atrial Natriuretic Factor; Autophagy; Cell Line; Cell Movement; Female; Humans; Mechanistic Target of Rapamycin Complex 1; Placenta; Pre-Eclampsia; Pregnancy; RNA, Small Interfering; Trophoblasts

Preeclampsia is associated with an increased lifelong risk of cardiovascular disease (CVD). It is not clear whether this is induced by persistent systemic organ and vascular damage following preeclampsia or due to a predisposition to both conditions that share cardiovascular pathophysiology. Common to both CVD and preeclampsia is the dysregulation of corin and its proteolytic product, atrial natriuretic peptide (ANP). ANP, a hypotensive hormone converted from pro-ANP by corin, is involved in blood pressure homeostasis. While corin is predominantly a cardiac enzyme, both corin and pro-ANP are significantly upregulated in the gravid uterus and dysregulated in preeclampsia. Relatively little is known about ANP function in the endothelium during a pregnancy complicated by preeclampsia. Here, we investigated the effect of ANP on endothelial cell proliferation and migration, markers of endothelial dysfunction, and receptor expression in omental arteries exposed to circulating preeclamptic toxins. ANP receptor expression is significantly upregulated in preeclamptic vasculature but not because of exposure to preeclampsia toxins tumour necrosis factor α or soluble fms-like tyrosine kinase-1. The supplementation of endothelial cells with ANP did not promote proliferation or migration, nor did ANP improve markers of endothelial dysfunction. The role of ANP in preeclampsia is unlikely to be via endothelial pathways.

Topics: Atrial Natriuretic Factor; Cardiovascular Diseases; Endothelial Cells; Endothelium; Female; Humans; Pre-Eclampsia; Pregnancy

We examined the heart failure biomarker mid-regional pro-atrial natriuretic peptide during the first trimester of pregnancy in relation to early-onset preeclampsia <34 weeks.. This case-control study included 34 women with singleton pregnancies with a preeclampsia diagnosis and delivery before 34 weeks of gestation who had attended the routine first-trimester ultrasound scan at 11-13+6 weeks of gestation between August 2010 and October 2015 at the Copenhagen University Hospital Rigshospitalet, Denmark, and 91 uncomplicated singleton pregnancies matched by time of the routine first-trimester blood sampling at 8-13+6 weeks. Descriptive statistical analyses were performed for maternal characteristics and obstetric and medical history for the case versus the control group. Concentrations of mid-regional pro-atrial natriuretic peptide, placental growth factor, soluble fms-like tyrosine kinase-1, and pregnancy-associated plasma protein A between early-onset preeclampsia cases and the control group were compared using Students t-test and the Mann-Whitney U test. Biochemical marker concentrations were converted into multiples of the expected median values after adjustment for gestational age.. Mid-regional pro-atrial natriuretic peptide levels were not significantly different between early-onset preeclampsia cases and the control group in the first trimester of pregnancy. As expected, both placental growth factor and pregnancy-associated plasma protein A levels were significantly lower in early-onset preeclampsia, whereas soluble fms-like tyrosine kinase-1 levels were not statistically significantly different.. The maternal first-trimester concentration of mid-regional pro-atrial natriuretic peptide, a peptide with multiple biological functions including a relation to cardiovascular disease, was not significantly different in women with early-onset preeclampsia.

Topics: Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Female; Gestational Age; Humans; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Vascular Endothelial Growth Factor Receptor-1

Topics: Atrial Natriuretic Factor; Biomarkers; Female; Heart Atria; Humans; Natriuretic Peptide, Brain; Pre-Eclampsia; Pregnancy; Ventricular Dysfunction, Left

Arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) may contribute to the pathogenesis of pre-eclampsia (PE), but their role remains to be elucidated. Our aims were to evaluate the surrogates of AVP and ANP, C-terminal pro-AVP (copeptin) and mid-regional pro-ANP (MR-proANP), as biomarkers for the prediction of PE-related pregnancy complications and whether they are associated with angiogenic markers and/or clinical manifestations of PE.. This was a retrospective analysis of a prospective cohort study that enrolled pregnant women with suspected or confirmed PE, between December 2013 and April 2016. From each patient, a blood sample was obtained at study entry and serum levels of copeptin, MR-proANP, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured. We evaluated the ability of sFlt-1, PlGF, sFlt-1/PlGF ratio, copeptin and MR-proANP, assessed either alone or combined with traditional predictors (gestational age, parity, diastolic blood pressure and proteinuria), to predict maternal complications and fetal/neonatal complications. Models were compared using concordance statistic (C-index).. A total of 526 women were evaluated in the study. Women with confirmed PE displayed elevated serum copeptin and MR-proANP levels in comparison to those with suspected PE but no hypertensive disease of pregnancy. When combined with traditional predictors, the sFlt-1/PlGF ratio displayed a higher C-index than copeptin and MR-proANP (0.76, 0.63 and 0.67, respectively, vs 0.60 for the traditional predictors alone) for the prediction of maternal complications. Similarly, for the prediction of fetal/neonatal complications, the sFlt-1/PlGF ratio displayed a higher C-index than copeptin and MR-proANP when added to the traditional model (0.83, 0.79 and 0.80, respectively, vs 0.79 for the traditional predictors alone). When subdividing women according to sFlt-1/PlGF ratio (≥ 85 vs < 85), no differences in copeptin levels were observed, while MR-proANP level was elevated in women with sFlt-1/PlGF ratio ≥ 85. Multiple regression analysis revealed that copeptin and MR-proANP were independent determinants of proteinuria.. Copeptin and MR-proANP have limited value in predicting PE-related complications when compared with the sFlt-1/PlGF ratio. However, both copeptin and MR-proANP were associated with proteinuria, with copeptin exerting this effect independently of the sFlt-1/PlGF ratio. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Female; Gestational Age; Glycopeptides; Humans; Maternal Serum Screening Tests; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Prospective Studies; Retrospective Studies; Vascular Endothelial Growth Factor Receptor-1

Corin is a protease that converts pro-atrial natriuretic peptide (pro-ANP) to ANP. While the involvement of ANP in the cardiovascular regulation is well established, there is increasing evidence that the pregnant uterus produces ANP, which promotes spiral artery remodeling. The present study examines the alterations in corin and PCSK6, a key enzyme in the conversion of pro-corin to corin, in the placenta of hyperinsulinemic dams (HD) featuring pregnancy-induced hypertension (PIH).. The study was conducted on female Wistar rats. Rats were rendered hyperinsulinemic by subcutaneous insulin pellet, mated and followed to the twenty-first day of pregnancy. Normal pregnant dams (NPD) served as controls. Both groups were sacrificed on day 21 of gestation and their placentas were dissected along with the mesometrial triangle (MT). The tissue was then sectioned from the maternal surface to the base of the MT, and processed for histological and molecular biology analysis of Corin, PCSK6 and ANP expression/immunoreactivity.. Hyperinsulinemic dams developed PIH, along lower placental and fetal weights. Corin expression and immunoreactivity were significantly decreased in the placenta by ~40-50%, but not in the MT. Similarly, placental but not MT PCSK6 immunoreactivity was lower in HD. Concomitantly with the downregulation of corin/PCSK6, proANP levels increased in the placenta of HD.. Corin and PCSK6 are expressed in the placenta and MT. The decline in these two enzymes in the placenta of HD suggests a role of corin/PCSK6 machinery in the development of PIH and intrauterine growth restriction characterizing hyperinsulinemia.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Down-Regulation; Female; Humans; Hyperinsulinism; Placenta; Pre-Eclampsia; Pregnancy; Proprotein Convertases; Rats; Rats, Wistar; Serine Endopeptidases

Midregional pro-atrial natriuretic peptide (MR-proANP) is a cardiac biomarker and the maternal serum levels could predict late-onset preeclampsia (PE) or intrauterine growth restriction (IUGR) at third trimester of pregnancy.. We measured MR-proANP between 32 and 37 weeks of pregnancy prospectively: 32 patients suffered from PE and 22 developed IUGR. 676 patients exhibited no pregnancy complications.. The median MR-proANP showed significantly higher results in PE (64.9 pmol/l (interquartile range (IQR) 36.3-105.2) and IUGR (59.7 pmol/l (IQR 39.7-163.0) groups compared to controls (38.7 pmol/l (IQR 29.7-49.2). Linear regression analysis showed association between PE and MR-proANP levels (Exp(ß) = 1.56; 95% CI: 1.34-1.81). AUC showed a predictive value for PE (AUC: 0.72) and IUGR (AUC: 0.71).. Measuring MR-proANP in maternal serum between 32 and 37 weeks of pregnancy could help predicting IUGR and PE diagnosed after 34 week in pregnancy. Thus, we assume that MR-proANP may be an additional biomarker which mirrors the maternal cardiosvascular status next to sFlt-1/PLGF representing the angiogenic status.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Female; Fetal Growth Retardation; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third

To better understand the profound multisystem changes in maternal physiology triggered by parturition, in particular in the underexplored neuronal system, by deploying a panel of pre- vs post-delivery maternal serum biomarkers, most notably the neuronal cytoskeleton constituent neurofilament light chain (NfL). This promising fluid biomarker is not only increasingly applied to investigate disease progression in numerous brain diseases, particularly in proteopathies, but also in detection of traumatic brain injury or monitoring neuroaxonal injury after ischemic stroke.. The study was nested within a prospective cohort study of pregnant women at risk of developing preeclampsia at the University Hospital of Basel. Paired ante- and postpartum levels of progesterone, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin (CT-proAVP), and NfL were measured in 56 women with complete clinical data.. Placental delivery significantly decreased all placental markers: progesterone 4.5-fold, PlGF 2.2-fold, and sFlt-1 1.7-fold. Copeptin and MR-proANP increased slightly (1.4- and 1.2-fold, respectively). Unexpectedly, NfL levels (median [interquartile range]) increased significantly post-partum: 49.4 (34.7-77.8) vs 27.7 (16.7-31.4) pg/ml (p < 0.0001). Antepartum NfL was the sole independent predictor of NfL peri-partum change; mode of delivery, duration of labor, clinical characteristics and other biomarkers were all unrelated. Antepartum NfL levels were themselves independently predicted only by maternal age.. Parturition per se increases maternal serum NfL levels, suggesting a possible impact of parturition on maternal neuronal integrity.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Cardiovascular System; Delivery, Obstetric; Female; Glycopeptides; Humans; Nervous System Physiological Phenomena; Neurofilament Proteins; Parturition; Placenta Growth Factor; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy, High-Risk; Progesterone; Prospective Studies; Risk Factors; Vascular Endothelial Growth Factor Receptor-1

BACKGROUND Atrial natriuretic peptide (ANP) is a cardiac hormone that regulates blood pressure and the salt-water balance in the blood. It acts through natriuretic peptide receptors (NPR), and the major biologically active ANP receptor is natriuretic peptide receptor-A (NPR-A). Aberrant forms of ANP and its receptors have been reported in patients with preeclampsia. However, whether aberrant forms of ANP or NPR-A are present in preeclamptic placenta, and what their role is in preeclampsia pathogenesis, has not yet been elucidated clearly. The aim of this study was to assess the expression of ANP and NPR-A in the placenta and decidua and its role in preeclampsia development. MATERIAL AND METHODS The expression of ANP and NPR-A in the first-trimester villous and decidua, full-term placenta, and preeclamptic placenta was determined using immunohistochemistry and Western blot analysis. The HTR8/SVneo cell line was used to investigate the role of NPR-A in proliferation, apoptosis, and invasion using Cell Counting Kit-8 analysis, flow cytometry analysis, and a Transwell invasion assay, respectively. RESULTS ANP and NPR-A were localized in the syncytiotrophoblasts, cytotrophoblasts, and trophoblast columns of human first-trimester villous trophoblast cells of decidua, and in the glandular epithelium and extravillous trophoblast cells of decidua. ANP-positive and NPR-A-positive cells in the decidual stroma were clustered around and infiltrated into the vascular wall of the spiral artery undergoing remodeling. NPR-A expression was significantly reduced in preeclamptic placentas, and NPR-A knockdown significantly impaired the invasion ability of HTR8/SVneo cells, although it had no effect on cell proliferation and apoptosis. CONCLUSIONS ANP and NPR-A are involved in human placental development. Decreased levels of NPR-A may contribute to the development of preeclampsia.

Topics: Adult; Apoptosis; Atrial Natriuretic Factor; Blotting, Western; Cell Line; Cell Proliferation; Decidua; Female; Gene Expression Profiling; Humans; Immunohistochemistry; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Receptors, Atrial Natriuretic Factor; Young Adult

To compare plasma N-terminal pro-atrial natriuretic peptide concentrations in preeclamptic patients and healthy normotensive pregnant women.. A cases-controls study was done with 180 patients at Hospital Central Dr. Urquinaona, Maracaibo, Venezuela, that included 90 preeclamptic patients (group A; cases) and 90 healthy normotensive pregnant women selected with the same age and body mass index similar to group A (group B; controls). Blood samples were collected one hour after admission and prior to administration of any medication in group A to determine plasma N-terminal pro-atrial natriuretic peptide and other laboratory parameters.. Plasma N-terminal pro-atrial natriuretic peptide concentrations in group A (mean 1.01 [0.26] pg/mL) showed a significant difference when compared with patients in group B (mean 0.55 [0.07] pg/mL; P<.001]. There was no significant correlation with systolic and diastolic blood pressure values in preeclamptic patients (P=ns). A cut-off value of 0.66ng/mL had an area under the curve of 0.93, sensitivity of 87.8%, specificity of 83.3%, a positive predictive value of 84.0% and a negative predictive value of 87.2%, with a diagnostic accuracy of 85.6%.. Preeclamptic patients have significantly higher concentrations of plasma N-terminal pro-atrial natriuretic peptide compared with healthy normotensive pregnant women, with high predictive values for diagnosis.

Topics: Adult; Area Under Curve; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Case-Control Studies; Female; Humans; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Protein Precursors; Reference Values; Sensitivity and Specificity

Corin is a serine protease that converts pro-atrial natriuretic peptide (pro-ANP) to atrial natriuretic peptide (ANP), a cardiac hormone that regulates salt-water balance and blood pressure. ANP is degraded by natriuretic peptide receptor (NPR). This study was to determine if aberrant pro-ANP/corin/NPR signaling is present in maternal vascular system in preeclampsia.. Maternal venous blood was obtained from 197 pregnant women (84 normotensive, 16 complicated with chronic hypertension (CHT), 11 mild and 86 severe preeclampsia). Plasma corin and pro-ANP concentrations were measured by enzyme-linked immunosorbent assay. Maternal subcutaneous fat tissue was obtained from 12 pregnant women with cesarean section delivery (6 normotensive and 6 preeclampsia). Vascular ANP and its receptors NPR-A, NPR-B, and NPR-C expression were examined by immunostaining of paraffin embedded subcutaneous fat tissue sections.. Corin concentrations were significantly higher in mild (2.78 ± 0.67 ng/ml, p < .05) and severe (2.53 ± 0.18 ng/ml, p < .01) preeclampsia than in normotensive (1.58 ± 0.08 ng/ml) and CHT (1.55 ± 0.20 ng/ml) groups. Pro-ANP concentrations were significantly higher in CHT (1.59 ± 0.53 ng/ml, p < .05) and severe preeclampsia (1.42 ± 0.24 ng/ml, p < .01) than in normotensive (0.48 ± 0.06 ng/ml) and mild preeclampsia (0.52 ± 0.09 ng/ml) groups. ANP and NPR-B expression was undetectable in maternal vessels from normotensive and preeclamptic pregnancies, but reduced NPR-A expression and increased NPR-C expression was found in maternal vessel endothelium in preeclampsia.. ANP is a vasodilator and NPR-C is a clearance receptor for ANP. The finding of upregulation of NPR-C expression suggests that circulating ANP clearance or degradation is increased in preeclampsia. These results also suggest that pro-ANP/corin/NPR signaling is dominant in the vascular system in preeclampsia.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Endothelium, Vascular; Female; Humans; Pre-Eclampsia; Pregnancy; Receptors, Atrial Natriuretic Factor; Serine Endopeptidases; Signal Transduction; Young Adult

Preeclampsia (PE) is a major cause of mortality of mothers, fetuses and newborns around the world. The etiology of preeclampsia has not yet been clarified, but many studies indicate a multifactorial basis of PE. Aldosterone synthase (CYP11B2) is responsible for synthesis of aldosterone responsible for regulating blood pressure. Similarly, natriuretic peptide (ANP) regulates blood pressure through a variety of mechanisms affecting the sodium concentration and the amount of extracellular fluid. Currently, attention is paid to the role of the polymorphisms in the expression level of these genes. The aim of the study was to determine the frequencies of genotypes and alleles for polymorphisms of -344C>T CYP11B2 gene and 2238T>C ANP gene in women with preeclampsia and healthy pregnant women from the Caucasian population.. The study included a group of 165 pregnant women (59 women with preeclampsia and 109 healthy pregnant women). DNA was extracted from peripheral blood. Determination of the polymorphism of -344C>T CYP11B2 gene and 2238T>C ANP gene was performed by PCR-RFLP method.. The results showed that the frequencies of the TC and CC genotypes of 2238T>C polymorphism in ANP gene were significantly higher in patients with PE compared to control group. For -344C>T polymorphism of CYP11B2 gene, the frequency of TT genotype was significantly higher in patients with hypertension than in controls (32.2% vs. 23.58%).. Our findings showed that gene polymorphism of CYP11B2 (-344C>T) and ANP (2238T>C) may be associated with developing PE during pregnancy.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Case-Control Studies; Cytochrome P-450 CYP11B2; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Hypertension, Pregnancy-Induced; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Pre-Eclampsia; Pregnancy; White People

The ANP knockout mouse is reported to exhibit pregnancy-associated hypertension, proteinuria and impaired placental trophoblast invasion and spiral artery remodeling, key features of pre-eclampsia (PE). We hypothesized that these mice may provide a relevant model of human PE with associated fetal growth restriction (FGR). Here, we investigated pregnancies of ANP wild type (ANP(+/+)), heterozygous (ANP(+/-)) and knockout (ANP(-/-)) mice. Maternal blood pressure did not differ between genotypes (E12.5, E17.5), and fetal weight (E18.5) was unaffected. Placental weight was greater in ANP(-/-) versus ANP(+/+) mice. Therefore, in our hands, the ANP model does not express phenotypic features of PE with FGR.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Disease Models, Animal; Female; Fetal Growth Retardation; Mice; Mice, Knockout; Placenta; Pre-Eclampsia; Pregnancy

Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast invasion and spiral artery remodeling. Yet, elevated maternal plasma atrial natriuretic peptide (ANP) and corin levels have been reported in pregnancies complicated by pre-eclampsia (PE). The aim of this study was to investigate longitudinal changes in maternal plasma levels of corin and mid-regional proatrial natriuretic peptide (MR-PANP) in pregnancies that develop PE and gestational hypertension (GH).. This was a nested case-control study drawn from a larger prospective longitudinal study in singleton pregnancies identified as being at high risk for PE by screening at 11 + 0 to 13 + 6 weeks' gestation. Blood samples were taken every 4 weeks until delivery. Values were compared in pregnancies that developed preterm PE (requiring delivery before 37 weeks' gestation), term PE, GH and those that remained normotensive.. A total of 471 samples were analyzed from 122 women, including 85 that remained normotensive, 12 that developed GH, 13 term PE and 12 preterm PE. In the normotensive group, log10 corin levels were associated with gestational age (P < 0.01), whereas log10 MR-PANP levels were not. In the preterm-PE group, compared with the normotensive group, corin was significantly lower until 20 weeks' gestation (P = 0.001). In the GH and term-PE groups, corin did not differ significantly from the normotensive group (P = 0.637 and P = 0.161, respectively). Compared with the normotensive group, MR-PANP levels were significantly higher in the pregnancies that developed preterm PE and GH (P = 0.046 and P = 0.019, respectively), but not term PE (P = 0.467).. Maternal-plasma corin and MR-PANP could potentially be useful biomarkers for the prediction of preterm PE.

Topics: Adult; Atrial Natriuretic Factor; Female; Humans; Hypertension, Pregnancy-Induced; Longitudinal Studies; Pre-Eclampsia; Pregnancy; Risk Factors; Serine Endopeptidases

We investigated the potential value of maternal serum copeptin, midregional proatrial natriuretic peptide (MR-proANP) and Procalcitonin (PCT) levels at 11-13 weeks' gestation in the prediction of preeclampsia (PE) in a case-control study.. Maternal serum concentration of copeptin, MR-proANP and PCT were measured at 11-13 weeks' gestation in cases of PE (n = 35) and controls (n = 100). The PE group was divided into early-onset PE (EO-PE) and late-onset PE (LO-PE). From the regression model, the value in each case and control was expressed as a multiple of the expected median (MoM). The Mann-Whitney test was used to determine the significance of differences in the median MoM in each outcome group from that in the controls.. In the PE group, compared to controls, maternal serum concentrations of copeptin, MR-proANP and PCT were not significantly different.. The maternal serum copeptin, MR-proANP and PCT levels are higher in EO-PE and LO-PE patients, but the difference is not significant. Thus, their levels in first trimester are not proven to be effective markers to screen for PE.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Gestational Age; Glycopeptides; Humans; Logistic Models; Male; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Protein Precursors

Topics: Atrial Natriuretic Factor; Female; Humans; Pre-Eclampsia; Pregnancy; Serine Endopeptidases

Topics: Atrial Natriuretic Factor; Female; Humans; Pre-Eclampsia; Pregnancy; Serine Endopeptidases

To investigate the ability of cardiovascular plasma biomarkers to identify imminent preeclampsia (PE) among pregnant women at triage.. C-terminal pro-arginine vasopressin (copeptin), C-terminal pro-endothelin-1 (CT-proET-1), mid-regional pro-adrenomedullin (MR-proADM), and mid-regional pro-atrial natriuretic peptide (MR-proANP) were prospectively measured in pregnant women presenting at the obstetrical triage units of the University Hospitals of Basel and Zurich, Switzerland. Logistic regression and receiver operating characteristics (ROC) analysis was used to assess and quantify the predictive ability of cardiovascular biomarkers.. Of the 147 included women, 27 (18.4%) were diagnosed at admission with PE. All biomarker levels were significantly higher in participants with PE as compared to controls. However, only MR-proANP, MR-proADM and CT-proET-1 were significant and independent predictors of PE, after taking into account the effect of various clinical confounders. The area under the ROC curve (AUC) was 0.62 (95% confidence interval 0.50-0.73) for copeptin, 0.64 (0.52-0.76) for MR-proADM, 0.71 (0.61-0.82) for CT-proET-1, and 0.83 (0.73-0.92) for MR-proANP. The combination of MR-proANP and MR-proADM resulted in the highest diagnostic performance (AUC 0.88; 0.79-0.96).. Assessment of the cardiovascular plasma biomarkers MR-proANP and MR-proADM holds promise to support diagnosis of PE at triage.

Topics: Adrenomedullin; Adult; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Endothelin-1; Epidemiologic Studies; Female; Glycopeptides; Humans; Peptide Fragments; Pre-Eclampsia; Pregnancy; Protein Precursors; Triage

In very preterm infants, clinical decision-making, such as closing a patent ductus arteriosus (PDA), may be aided by measuring circulating natriuretic and endothelial pro-peptides.. To investigate the association between perinatal characteristics, PDA echocardiography and plasma concentrations of stable pro-peptides of B-type natriuretic peptide (NT-proBNP), atrial natriuretic peptide (MR-proANP) and endothelin-1 (CT-proET-1).. A prospective, cross-sectional, single-center study was performed in 66 infants who were less than 32 weeks of gestational age. Pro-peptide concentrations were determined at birth and at day 2-3 of life.. Plasma concentrations of all 3 pro-peptides increased on average 2- to 5-fold from birth to day 2-3 of life. NT-proBNP and MR-proANP were closely related at birth and at day 2-3 (Rs 0.902 and 0.897, respectively, p < 0.001), whereas CT-proET-1 was related to NT-proBNP and MR-proANP at birth (Rs 0.478 and 0.460, respectively, p < 0.001) but not at day 2-3. Birth weight was negatively related to all 3 pro-peptides at birth (p < 0.01); however, preeclampsia and compromised placental perfusion were associated with elevated NT-proBNP and MR-proANP concentrations at birth. At day 2-3, MR-proANP and NT-proBNP correlated significantly with the ductal diameter (Rs 0.416 and 0.415, respectively, both p = 0.011), whereas CT-proET-1 correlated with the left atrium/aorta ratio (Rs 0.506, p = 0.027). CT-proET-1 was elevated in infants with treated compared to untreated PDA [median (5-95% range) 388 (272-723) vs. 303 (152-422) pmol/l, p = 0.011], but not NT-proBNP or MR-proANP.. CT-proET-1 is a promising predictor in determining the need for PDA intervention.

Topics: Atrial Natriuretic Factor; Ductus Arteriosus, Patent; Echocardiography; Endothelin-1; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Placenta; Pre-Eclampsia; Pregnancy; Protein Precursors

Preeclampsia is associated with increased risk of cardiovascular disease. Midregional proatrial natriuretic peptide (MR-proANP), a precursor of the atrial natriuretic peptide, is a biomarker for cardiovascular disease. We obtained plasma from 184 pregnant women in gestational weeks 24 to 42 (normotensive pregnancies: n=77, preeclampsia: n=107), from 25 of these women at 5 to 8 years after index pregnancy (normotensive pregnancies: n=11, preeclampsia: n=14), and from 49 normotensive, nonpregnant women and analyzed them by immunoassay for MR-proANP. To investigate potential sources, placental and decidual atrial natriuretic peptide mRNA expression levels were analyzed by quantitative real-time PCR in 21 normotensive and 23 preeclamptic pregnancies, as well as in human heart and kidney samples. For further confirmation, we measured circulating MR-proANP and performed expression studies in a transgenic rat model for preeclampsia. MR-proANP was significantly elevated in maternal plasma in preeclampsia compared with normotensive pregnancies (135 versus 56 pmol/L; P<0.001). However, 5 to 8 years after pregnancy, there was no difference (formerly preeclamptic women versus formerly normotensive in pregnancy: 53 versus 49 pmol/L; P=0.5). Our preeclamptic rat model confirmed the acute MR-proANP differences between preeclamptic and normotensive pregnancies (10.9±1.9 versus 4.3±0.3 pmol/L; P=0.05). Atrial natriuretic peptide expression was high in the heart but negligible in the uteroplacental unit in both normotensive humans and rats, whereas expression in maternal and fetal hearts in the preeclamptic rats was significantly increased, compared with controls. MR-proANP is a serviceable biomarker in preeclampsia, both in humans and a rat model, probably reflecting cardiovascular hemodynamic stress.

Topics: Adult; Animals; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Disease Models, Animal; Female; Humans; Kidney; Myocardium; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Rats; Rats, Transgenic; Risk Factors; RNA, Messenger

In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Case-Control Studies; Cells, Cultured; Disease Models, Animal; Female; Gene Expression Regulation; HEK293 Cells; Humans; Ischemia; Kidney; Kidney Diseases; Mice; Mice, Knockout; Mice, Transgenic; Mutation; Pre-Eclampsia; Pregnancy; Serine Endopeptidases; Trophoblasts; Uterine Artery; Uterus

The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting that preeclampsia is associated with cardiovascular changes in early pregnancy.

Topics: Adult; Atrial Natriuretic Factor; Diabetes Mellitus, Type 1; Female; Gestational Age; Humans; Natriuretic Peptide, Brain; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Young Adult

The purpose of this study was to evaluate the relationship between natriuretic peptides (NT-proANP and NT-proBNP) and hemodynamic parameters in preeclampsia.. This was a cross-sectional study of 19 preeclamptic, 15 chronic hypertensive, and 26 normotensive women in the third trimester of pregnancy. Stroke index (SI), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and left cardiac work index (LCWI) were derived by whole-body impedance cardiography. Systolic blood pressure (SAP), diastolic blood pressure (DAP), and mean arterial pressure (MAP) were measured. The plasma levels of NT-proANP and NT-proBNP were determined with radioimmunoassays.. NT-proANP and NT-proBNP concentrations were significantly higher in preeclamptic women compared to chronic hypertensive and normotensive pregnancies. Preeclamptic women had lower CI and HR and higher SAP, MAP, and SVRI than the control groups. In preeclampsia NT-proANP correlated significantly with SAP and SVRI; meanwhile, NT-proBNP correlated significantly with SVRI and CI. These correlations persisted in the subgroup of nonmedicated preeclamptic women, except in the case of NT-proBNP and CI.. High NT-proANP and NT-proBNP concentrations in preeclampsia reflect the strain on the heart caused by high afterload, rather than the function of the heart expressed as SI or CI.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Chronic Disease; Cross-Sectional Studies; Female; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Placental Circulation; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Third; Probability; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index

Pregnancy induces a smaller rise in plasma volume in formerly preeclamptic women with a pre-existent subnormal plasma volume than in their counterparts with a normal plasma volume. These women also have a three times higher recurrence rate of pregnancy-induced hypertensive disorders. In this study we tested the hypothesis that a subnormal plasma volume in these women is related to a lower capacitance of their venous compartment.. In 31 nonpregnant formerly preeclamptic women with a subnormal plasma volume and eight parous controls, we infused intravenously 500 mL of a modified gelatin solution over 30 minutes. Before and after infusion we measured the circulating levels of alpha-atrial natriuretic peptide (alpha-ANP) and active plasma renin concentration (APRC). During volume loading, we recorded the change in heart rate, stroke volume, and cardiac output using pulse contour analysis. We measured the ratio of percent change in blood volume and percent change in cardiac output during volume loading as a marker for venous capacitance.. During volume loading, patients differed from controls by a larger rise in alpha-ANP, pulse rate, and cardiac output, and by a lower estimated venous capacitance. The concomitant response of stroke volume and APRC did not differ appreciably between groups.. Formerly preeclamptic women with a subnormal plasma volume differ from controls with a normal plasma volume by a reduced venous capacitance. These results support our hypothesis that, in these women, a subnormal plasma volume indicates the presence of a subnormal venous capacitance.

Topics: Adult; Atrial Natriuretic Factor; Cardiac Output; Female; Heart Rate; Hematocrit; Humans; Plasma Volume; Pre-Eclampsia; Pregnancy; Renin; Statistics, Nonparametric; Stroke Volume; Vascular Capacitance

In formerly preeclamptic women with a low plasma volume, the recurrence rate of preeclampsia is higher than in women with a normal prepregnant plasma volume. In a recent study, we demonstrated that the low plasma volume subgroup also had a subnormal venous capacitance. In the present study, we determined the impact of subnormal plasma volume on the hemodynamic response to moderate exercise.. We performed this study in the follicular phase of the menstrual cycle, in 31 formerly preeclamptic women with a subnormal plasma volume (low-PV) and eight parous controls. The exercise consisted of 60 minutes of cycling in the supine position at 35% of the individualized maximum capacity. Before, during, and after cycling, we measured the percentage change in heart rate, stroke volume, and cardiac output. Before and after exercise, we measured the effective renal plasma flow (ERPF, para-amino-hippurate [PAH] clearance), glomerular filtration rate (GFR, inulin clearance), circulating levels of alpha-atrial natriuretic peptide (alpha-ANP), and active plasma renin concentration (APRC).. The response to exercise of formerly preeclamptic women with a subnormal plasma volume differed from that in controls by a lack of rise in stroke volume, a smaller rise in cardiac output and alpha-ANP, and a greater fall in GFR. The responses in heart rate, ERPF, and APRC did not differ between the two groups.. The response to moderate exercise of formerly preeclamptic women with a subnormal plasma volume differs from that in healthy parous controls with a normal plasma volume and suggests a lower capacity to raise venous return in conditions of a higher demand for systemic flow. The lower capacity to raise venous return in these conditions is associated with more cardiovascular drift. The physiologic consequence is a lower aerobic endurance performance during moderate exercise.

Topics: Adult; Atrial Natriuretic Factor; Cardiac Output; Exercise; Female; Glomerular Filtration Rate; Heart Rate; Humans; Logistic Models; Plasma Volume; Pre-Eclampsia; Pregnancy; Renal Plasma Flow; Renin; Stroke Volume; Vascular Capacitance

The majority of women with a history of preeclampsia have either an underlying thrombophilic disorder or a vascular disorder. In this study, we tested the hypothesis that only the latter condition predisposes for abnormal hemodynamic adaptation to pregnancy.. Thirty-seven formerly preeclamptic subjects were subdivided into a hypertensive (HYPERT, N = 10), a normotensive thrombophilic (THROMB, N = 13) and a normotensive nonthrombophilic subgroup (NONTHROMB, N = 14). In these women and in 10 normal parous controls, the following variables were measured at least five-months postpartum at day 5 (+/-2) of the menstrual cycle and again at five- and seven-weeks amenorrhea in the next pregnancy: mean arterial pressure, heart rate, cardiac output, central cardiovascular dimensions, plasma volume, glomerular filtration rate, effective renal plasma flow, 17-beta estradiol, progesterone, the hormones of the renin-angiotensin-aldosterone (RAAS) axis, catecholamines and alpha-atrial natriuretic peptide.. The early pregnancy rise in cardiac output, renal variables, RAAS activity, and plasma volume was comparable in all groups. However, the HYPERT and NONTHROMB subgroups differed from controls by a lower plasma volume in the prepregnant state. In addition, only the women in these two subgroups responded to pregnancy by a rise in circulating alpha-atrial natriuretic peptide. In addition, at seven weeks, in the subjects belonging to the HYPERT and NONTHROMB subgroups, plasma volume was the lowest and correlated inversely with the concomitant circulating level of alpha-atrial natriuretic peptide.. The hemodynamic adaptation to pregnancy in the HYPERT and NONTHROMB subgroups differs from that in THROMB and controls by an early pregnancy rise in alpha-atrial natriuretic peptide. As a consequence, the early pregnancy plasma volume expansion in the NONTHROMB and HYPERT subgroups is less than in normal parous controls.

Topics: Adaptation, Physiological; Adult; Atrial Natriuretic Factor; Blood Volume; Female; Hemodynamics; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Reference Values; Thrombophilia

Among women with a history of preeclampsia the prevalence of hemodynamic and clotting disorders is elevated. In this study we tested the hypothesis that the normal cyclic variation in hemodynamic and renal function parameters with the menstrual cycle that is seen among healthy women would be preserved in women with a history of preeclampsia irrespective of whether they had an underlying hemodynamic or clotting disorder.. We compared the hemodynamic and volume cyclic variations during the menstrual cycle among women with a history of preeclampsia (n = 39) with those among healthy parous control women (control group, n = 10). The participants with a history of preeclampsia were subdivided into groups of women with hypertension with or without thrombophilia (hypertension group, n = 10), women with a normotension and a thrombophilic disorder (thrombophilia group, n = 17), and women without either of these abnormalities (symptom-free group, n = 12). We measured > or =5 months post partum, once during the follicular phase of the menstrual cycle (day 5 +/- 2) and once during the luteal phase (day 22 +/- 2), the following variables: body weight and length, mean arterial pressure, heart rate, cardiac output, plasma volume, glomerular filtration rate, effective renal plasma flow, and concentrations of renal volume homeostatic hormones, reproductive hormones, and catecholamines. From the measured data we calculated body mass index, cardiac index, left ventricular work, total peripheral and renal vascular resistances, effective renal blood flow, and renal filtration fraction.. The hypertension group differed from the control group in having higher baseline (follicular phase) values for cardiac output, cardiac output, left ventricular work, renal vascular resistance, and atrial natriuretic peptide and norepinephrine levels. The symptom-free group differed from the control group in having a lower baseline plasma volume and higher baseline cardiac output and left ventricular work values. Women in the thrombophilia group were comparable to those in the control group with respect to baseline hemodynamic and renal function variables except for a higher renal vascular work value. In the control group heart rate, plasma volume, effective renal plasma volume, effective renal blood flow, and concentrations of renin-angiotensin-aldosterone system hormones and norepinephrine were increased during the luteal phase with respect to values during the follicular phase, whereas the renal vascular resistance and atrial natriuretic peptide values were decreased. In the three subgroups of women with a history of preeclampsia this cyclic pattern with the menstrual cycle was preserved for most of these parameters.. Although baseline hemodynamic and volume status among women with a history of preeclampsia differed from that among healthy parous control subjects, the cyclic variation with the menstrual cycle was largely preserved.

Topics: Atrial Natriuretic Factor; Blood Flow Velocity; Blood Pressure; Blood Volume; Cardiac Output; Female; Follicular Phase; Glomerular Filtration Rate; Heart Rate; Hemodynamics; Homeostasis; Humans; Hypertension; Kidney; Luteal Phase; Menstrual Cycle; Norepinephrine; Pre-Eclampsia; Pregnancy; Thrombophilia; Vascular Resistance

This study was done to evaluate left ventricular structure and function among pregnant patients with preeclampsia and compare them with those of normotensive pregnant and nonpregnant subjects. It also tested the hypothesis that abnormalities in left ventricular structure and function are associated with elevated plasma levels of natriuretic peptides.. The study compared 75 pregnant women (n = 40 with preeclampsia; n = 35 normotensive pregnant women) and 10 nonpregnant normotensive control subjects undergoing an echocardiographic and biohumoral (renin activity and aldosterone, atrial natriuretic peptide, and brain natriuretic peptide concentrations) evaluation. The statistical analysis was carried out by analysis of variance, and significance was set at P <.05.. Comparison of pregnant patients with preeclampsia versus both normotensive pregnant women and nonpregnant women showed significant increases in left ventricular mass and left ventricular endsystolic and end-diastolic volumes and significant reductions in left ventricular ejection fraction and percentage of fractional shortening. These changes coincided with increases in plasma levels of atrial natriuretic peptide and brain natriuretic peptide that were linearly related to the left ventricular structural and functional changes observed in patients with preeclampsia.. Pregnant patients with preeclampsia showed adaptation to the increase in systemic blood pressure, with significant modification of left ventricular structure and function related to the plasma levels of both atrial natriuretic peptide and brain natriuretic peptide. A simple evaluation of plasma natriuretic peptide concentrations could help to discriminate patients with preeclampsia who have a condition of mild left ventricular overload.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Echocardiography; Female; Gestational Age; Heart Ventricles; Hemodynamics; Humans; Natriuretic Peptide, Brain; Pre-Eclampsia; Pregnancy; Renin; Ventricular Function, Left

We investigated the characteristic changes in histamine-induced, endothelium-derived nitric oxide (NO)-mediated relaxation in human omental resistance arteries seen in pre-eclampsia. Isometric contraction was provoked by a stable analogue of thromboxane A(2) in endothelium-intact strips from both pre-eclamptic and normotensive pregnant women. Histamine (0.3 nM-10 microM) produced a concentration-dependent relaxation of this contraction in both groups. The magnitude of the relaxation induced by histamine (1 microM) was significantly smaller in pre-eclampsia both in the presence and absence of famotidine (H(2)-receptor blocker). In the presence of famotidine, L-N(G)-nitroarginine significantly attenuated the histamine-induced relaxation in strips from normotensive pregnant women but not in those from pre-eclamptic women. The relaxation induced by human atrial natriuretic peptide (0. 1 nM-1 microM) was also significantly smaller in the pre-eclamptic group. It is concluded that the histamine-induced, endothelium-derived NO-mediated relaxation (mediated via H(1)-receptors) is down-regulated in resistance arteries in pre-eclampsia and we suggest that this is due, at least in part, to an attenuation of the action of cyclic GMP in smooth muscle cells.

Topics: Adult; Arteries; Atrial Natriuretic Factor; Cyclic GMP; Down-Regulation; Endothelium, Vascular; Famotidine; Female; Histamine; Humans; Isometric Contraction; Muscle, Smooth, Vascular; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitroarginine; Pre-Eclampsia; Pregnancy; Pyrilamine; Receptors, Histamine H1; Receptors, Histamine H2; Vascular Resistance; Vasodilation

Adrenomedullin (AM) is a peptide that elicits a long-lasting vasorelaxant activity, while atrial natriuretic peptide (ANP) has also been shown to be a potent vasodilatory agent. To clarify the possible role of AM and ANP in the physiology of pregnancy and pathophysiology of pre-eclampsia, we measured plasma concentrations of these peptides in non-pregnant women, normal pregnant women and women with pre-eclampsia. A gradual increase in plasma AM was observed as pregnancy progressed. The plasma AM concentrations during the second trimester (12.7 +/- 1.4 fmol/ml) were significantly elevated, in comparison with the non-pregnant follicular phase (6.4 +/- 0.61 fmol/ml), luteal phase (6.0 +/- 0.49 fmol/ml), and the first trimester (6.5 +/- 0.8 fmol/ml). The plasma AM concentrations of the third trimester (21.5 +/- 1.4 fmol/ml) were significantly elevated when compared with those of the second trimester (P < 0.05). Northern blot analysis confirmed the expression of the AM mRNA transcript (1.6 kb) in third trimester placentas. In comparison with those observed at term (25.3 +/- 4.5 fmol/ml), the plasma concentrations were significantly reduced post-partum (6.4 +/- 0.6 fmol/ml). In the third trimester, plasma AM concentrations did not differ significantly between women with pre-eclampsia (17.2 +/- 2.3 fmol/ml) and normal pregnant women. In contrast, the plasma ANP concentrations in pre-eclampsia (39.5 +/- 7. 1 pg/ml) were significantly elevated when compared with those of the normal third trimester (14.4 +/- 1.4 pg/ml) (P < 0.05). ANP concentrations were reasonably constant throughout the pregnancy.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Female; Follicular Phase; Gene Expression; Humans; Luteal Phase; Peptides; Placenta; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy Trimester, Third; RNA, Messenger

Changes in vasoactive hormones are reported to play an important role in the pathogenesis of preeclampsia linking placental hypoperfusion with hypertension, systemic disease, and proteinuria. We, therefore, studied diurnal patterns of vasoactive hormones in mild preeclampsia.. Venous blood samples were drawn every 2 h over 25 h for measurements of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, renin activity, and aldosterone and two urine collections (12 h each) for stable prostaglandin metabolite measurements. The patients were nine women with mild preeclampsia and, for comparison, nine control women matched for gestation and parity.. Women with mild preeclampsia had higher norepinephrine levels throughout 25 h, and lower systemic prostacyclin production as measured by the urinary 2,3-dinor-6-keto PGF1 alpha excretion during the daytime. Plasma endothelin and ANP and BNP concentrations tended to be higher throughout 25 h in preeclampsia, but differences between the two groups did not reach levels of statistical significance. Plasma renin activity and aldosterone did not differ between the groups. Whereas control women exhibited a diurnal variation in plasma norepinephrine, ANP, BNP, and aldosterone, and in both urinary prostacyclin and thromboxane A2 metabolites, this was less distinct or absent in patients with mild preeclampsia.. We conclude that mild preeclampsia is associated with elevated plasma norepinephrine levels, lower systemic daytime production of prostacyclin, and blunting of the normal diurnal variation for a number of indices including plasma levels of BNP, ANP, norepinephrine, and aldosterone, and urinary prostacyclin metabolites.

Topics: Adult; Aldosterone; Analysis of Variance; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Female; Humans; Linear Models; Nerve Tissue Proteins; Norepinephrine; Pre-Eclampsia; Pregnancy; Prostaglandins; Radioimmunoassay; Renin

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.

Topics: Atrial Natriuretic Factor; Equipment Design; Female; Guanylate Cyclase; Humans; Placenta; Pre-Eclampsia; Pregnancy; Vascular Resistance

To determine whether maternal midtrimester serum N-terminal peptide of proatrial natriuretic peptide, free beta subunit of human chorionic gonadotropin (hCGbeta), or alpha-fetoprotein (AFP) levels can predict preeclampsia.. A population-based cohort included 1037 nulliparous women, of whom 637 (61%) participated in a maternal serum Down syndrome screening program. Measurements of hCGbeta, AFP, and N-terminal peptide of proatrial natriuretic peptide were made from maternal serum collected at 15-19 weeks' gestation. Sensitivity, specificity, and predictive values were calculated for elevated AFP (at least 2.0 multiples of the median [MoM]) and hCGbeta (at least 2.0 MoM) values.. No difference was found in the concentrations of the N-terminal peptide of proatrial natriuretic peptide among the 30 women in whom preeclampsia developed later (median 270 [range 142-604] pmol/L) compared with 536 women who remained normotensive (274 [51-2626] pmol/L). The sensitivity and specificity of elevated AFP in predicting preeclampsia were 3% and 98% and those of elevated hCGbeta were 20% and 84%, respectively. When a stepwise multiple logistic regression model was used, only mean arterial pressure was an independent risk factor in predicting preeclampsia.. Determinations of the proposed new marker N-terminal peptide of proatrial natriuretic peptide, as well as serum hCGbeta or AFP, are not helpful in predicting preeclampsia.

Topics: Adult; alpha-Fetoproteins; Atrial Natriuretic Factor; Biomarkers; Chorionic Gonadotropin, beta Subunit, Human; Cohort Studies; Female; Humans; Logistic Models; Mass Screening; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Second; Protein Precursors; Risk Factors; Sensitivity and Specificity

The objective was to test the hypothesis that women with a recent history of preeclampsia have abnormalities in renal hemodynamics and volume status.. We studied a group of 26 primiparous women with history of preeclampsia and a group of 12 parous women with a history of uneventful pregnancies (control group). At least 4 months post partum we compared the following variables between these groups: effective renal plasma flow, glomerular filtration rate, plasma volume, plasma concentration of active renin, plasma concentration of angiotensin II, plasma concentration of aldosterone, and plasma concentration of atrial natriuretic peptide.. Both plasma volume and plasma concentration of atrial natriuretic peptide were lower in the formerly preeclamptic group. Compared with the control subjects, the formerly preeclamptic group also had a lower effective renal plasma flow, a higher filtration fraction, and a higher renal vascular resistance. Intergroup differences in plasma concentration of active renin, plasma concentration of angiotensin II and plasma concentration of aldosterone were small and inconsistent.. Women with history of preeclampsia are relatively hypovolemic and tend to have lower effective renal plasma flow and higher renal vascular resistance and filtration fraction than do control subjects. These findings support the hypothesis that otherwise healthy women with a history of preeclampsia show abnormalities in their volume status and renal hemodynamics, irrespective of their blood pressure.

Topics: Adult; Atrial Natriuretic Factor; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Medical Records; Plasma Volume; Postpartum Period; Pre-Eclampsia; Pregnancy; Reference Values; Renal Circulation; Vascular Resistance

Topics: Atrial Natriuretic Factor; Female; Humans; Pre-Eclampsia; Pregnancy

To determine whether increased concentrations of the N-terminal peptide of proatrial natriuretic peptide and of atrial natriuretic peptide are related to the severity of preeclampsia and gestational hypertension.. Blood samples were collected from 70 healthy pregnant women, 48 women with preeclampsia, and 19 women with gestational hypertension in the third trimester. We used a specific radioimmunoassay (RIA) method suitable for the determination of the plasma N-terminal peptide of proatrial natriuretic peptide in unextracted plasma. The atrial natriuretic peptide was measured by RIA from Sep-Pak C18-extracted plasma.. The N-terminal peptide of proatrial natriuretic peptide levels were significantly higher in preeclamptic women than in healthy pregnant controls (median 571 [range 189-2000] versus 266 pmol/L [80-634], P < .001) and also significantly higher in women with severe preeclampsia than in women with mild preeclampsia (766 [431-2000] versus 492 pmol/L [189-1283], P = .01). The N-terminal peptide of proatrial natriuretic peptide values were significantly elevated in the subgroup of hypertensive pregnancies with abnormal Doppler velocimetry. At entry into the study the values for the N-terminal peptide of proatrial natriuretic peptide were higher in the subgroup of women who developed severe preeclampsia and/or gave birth to a small for gestational age (SGA) infant compared to the values in the subgroup of women in whom the hypertensive condition remained stable (710 [271-1475] versus 407 pmol/L [189-1067], P = .006). Similar comparisons of atrial natriuretic peptide values did not reach significant differences.. The levels of N-terminal peptide of proatrial natriuretic peptide were higher in women with preeclampsia than in those with gestational hypertension and higher in women with gestational hypertension than in those with normal pregnancies. A marked elevation in N-terminal peptide of proatrial natriuretic peptide may predict development of severe preeclampsia and/or an SGA infant.

Topics: Adult; Atrial Natriuretic Factor; Case-Control Studies; Female; Gestational Age; Humans; Hypertension; Infant, Newborn; Infant, Small for Gestational Age; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Third; Protein Precursors; Severity of Illness Index; Ultrasonography

Topics: Aldosterone; Atrial Natriuretic Factor; Creatinine; Female; Humans; Kallikreins; Pre-Eclampsia; Predictive Value of Tests; Pregnancy

Various biochemical tests, suggested to be of value in the prediction of pre-eclampsia, have been evaluated. Some of these tests are currently available for use clinical, whereas others exist only in the laboratory. None, however, has been found to fulfil all desired criteria for the prediction of the development of pre-eclampsia.

Topics: Atrial Natriuretic Factor; Blood Coagulation Factors; Calcium; Endothelium, Vascular; Female; Humans; Platelet Count; Pre-Eclampsia; Pregnancy; Uric Acid

To further elucidate the role of atrial natriuretic peptide (ANP) in preeclampsia, its metabolic clearance (MCRANP) was determined concomitantly with its effects on sodium excretion (UNa), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF). Ten untreated preeclamptic primigravidae (PET) were studied at 29-37 wk gestation and again 4 mo postpartum (PP). Basal plasma concentration of ANP was significantly increased in PET compared with PP (14.8 +/- 1.9 vs. 4.1 +/- 0.5 pmol/l, respectively; P < 0.0001). MCRANP in PET and PP was 5.0 +/- 0.8 and 4.9 +/- 0.5 l/min [not significant (NS)], respectively. In PET, infusion of ANP produced (basal vs. ANP) a natriuresis (UNa 0.14 +/- 0.02 vs. 0.28 +/- 0.04 mmol/min, P < 0.001) and an increase in GFR (97 +/- 7 vs. 106 +/- 8 ml/min, P < 0.05), with ERPF unchanged (609 +/- 24 vs. 634 +/- 29 ml/min, NS). In PP, ANP infusion also produced a natriuresis (UNa 0.20 +/- 0.02 vs. 0.25 +/- 0.02 mmol/min, P = 0.01), no significant change in GFR (109 +/- 7 vs. 102 +/- 4 ml/min), and a significant reduction in ERPF (514 +/- 22 vs. 409 +/- 18 ml/min, P < 0.0001). Analysis of variance demonstrated a greater natriuretic effect of ANP in PET compared with PP (P < 0.05), similarly a significant difference in the effect of ANP on ERPF (P < 0.01) and GFR (P < 0.05) was seen but not on filtration fraction (P = 0.35).

Topics: Adult; Atrial Natriuretic Factor; Female; Gestational Age; Glomerular Filtration Rate; Hemodynamics; Humans; Infusions, Intravenous; Kidney; Metabolic Clearance Rate; Multivariate Analysis; Natriuresis; Parity; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Proteinuria; Regional Blood Flow; Renal Circulation; Sodium

One of the possible mechanisms responsible for pre-eclampsia is a loss of efficiency of the L-arginine-nitric oxide pathway with subsequent inactivation of the guanylyl cyclases of the vascular smooth muscle cells. As a result there should be a decrease in plasma cyclic 3'-5' guanosine monophosphate (cGMP) concentrations in pre-eclampsia. We assessed the behavior of this nucleotid in the plasma of pre-eclamptic women.. Sixteen pre-eclamptic women, 16 normotensive pregnant women matched for gestational age and six nonpregnant controls were investigated. Arterial blood pressure was recorded at inclusion time and then once-a-day until the fourth day after delivery concomitantly with the collection of blood samples for determining plasma cGMP, atrial natriuretic peptides (ANP), creatinine, uric acid and platelet counts. Also 24 h urines were simultaneously collected to calculate renal clearance of cGMP.. Before the initiation of antihypertensive treatment, plasma cGMP levels were significantly higher (p < 0.01) in pre-eclampsia women as compared both to pregnant normotensive controls and nonpregnant women (7.02 +/- 0.9 versus 4.8 +/- 0.76 versus 1.93 +/- 0.15 pmol.ml-1, p < 0.01). Under antihypertensive treatment, cGMP levels decreased significantly (p < 0.05) to 5.48 +/- 0.9 pmol.ml-1. The increase of plasma cGMP was associated with high ANP levels; the likelihood that a renal impairment could account for an increase in plasma cGMP was ruled out because the clearance of creatinine was not impaired. Similarly the possibility of a significant linear correlation between cGMP levels and blood pressure values or biological data was excluded in these women.. Plasma cGMP concentrations are increased in pre-eclampsia. They decrease to control values when blood pressure returns to normal values; they indicate enhanced guanylyl cyclase activation by ANP and additional factors, but cannot be considered as a direct index of the severity of pre-eclampsia.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Female; Guanylate Cyclase; Humans; Hypertension; Nitric Oxide; Parity; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular

To measure plasma atrial natriuretic peptide (ANP) in relation to maternal haemodynamics and body fluid balance in the early puerperium following uncomplicated pregnancy and pre-eclampsia.. A longitudinal study from late pregnancy and into the early postpartum period (days 1 to 3 and days 4 to 6) compared with nonpregnant controls.. Eleven women with uncomplicated pregnancies, 12 women with pre-eclampsia and 12 healthy, nonpregnant women.. Maternal heart dimensions determined by M-mode echocardiography, concentrations of ANP, and daily urine output and sodium excretion.. After delivery increases in left atrial dimensions, represented as mean (SEM), from 33.2 (1.6) to 37.7 (1.7) mm and ANP levels from 7.9 (1.1) to 19.0 (2.7) pmol/L were observed at 1-3 days postpartum in normal pregnant women, but we were not able to demonstrate a significant increase in diuresis and natriuresis. In the third trimester left atrial dimensions (38.4 (1.2) mm) and ANP levels (15.4 (2.2) pmol/L) were greater in pre-eclampsia. ANP levels rose further in pre-eclamptic women in the early puerperium (27.4 (7.4) pmol/L) with an increase in diuresis and natriuresis, while left atrial dimensions did not change significantly (39.4 (1.7) mm). A pericardial effusion was found in 11 pre-eclamptic but in only three healthy pregnant women.. A concommitant increase in left atrial dimensions and ANP in the early puerperium following uncomplicated pregnancies is consistent with the mechanism of atrial stretch as a stimulus for ANP release, although the biological significance of this finding remained unclear. A significantly higher release of ANP in the early puerperium after pregnancies complicated by pre-eclampsia may be a mechanism which promotes the renal elimination of excessive body fluids and sodium.

Topics: Adult; Atrial Natriuretic Factor; Echocardiography; Female; Heart Atria; Humans; Longitudinal Studies; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third

The study was undertaken to measure both plasma arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) concentrations in normal and preeclamptic pregnancies to elucidate the mechanisms of plasma volume regulation during pregnancy. The mean plasma AVP concentration in healthy pregnant women was much lower than nonpregnant controls; however, the concentration in preeclamptic patients was similar to that in the comparative period of normal pregnancy. Despite volume expansion, the mean plasma concentration of ANP in normal pregnancy showed no changes compared to nonpregnant controls. The concentration of plasma ANP in patients complicated by mild preeclampsia was higher than that in normal pregnant women. The concentration of plasma ANP in those with severe preeclampsia was much higher roughly in proportion to the severity of the disease. It is inferable that the lowered concentration of plasma AVP is involved in plasma volume expansion in normal pregnancy, largely but not in a depletion of plasma volume in preeclampsia. The elevated concentration of plasma ANP appears to be closely related to impaired plasma volume expansion in preeclampsia.

Topics: Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Female; Humans; Pre-Eclampsia; Pregnancy

The haemodynamic effect of volume load at elective Caesarean delivery may be modulated by atrial natriuretic peptide (ANP) especially in pre-eclamptic women in whom basal ANP levels are increased.. We followed the haemodynamic parameters and determined the peripheral venous levels of ANP before and after an intravenous volume preload of 1000 ml of Ringer's acetate solution, followed by a further load of the same volume under spinal anaesthesia in 7 healthy and in 6 pre-eclamptic women.. During the preload period the median ANP level increased more (from 14.8 to 22.1 pmol/l, P = 0.03) in pre-eclamptic than in healthy women (from 8.0 to 8.5 pmol/l, NS); while an increment in central venous pressure (CVP) was also greater in pre-eclamptic than in healthy women. The increase in the concentrations of ANP correlated significantly (P < 0.05) with the increase in CVP in the total study group. A significant increase in ANP levels in healthy pregnant women was not seen until during the second infusion period under spinal anaesthesia; in pre-eclamptic women the levels increased further during that period.. These findings concur with the theory that atrial stretch is a stimulus for ANP release. An exaggerated release of ANP in response to volume loading may aid in the adaptation of maternal circulation to volume load at elective Caesarean delivery in pre-eclamptic women.

Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Atrial Natriuretic Factor; Blood Volume; Central Venous Pressure; Cesarean Section; Female; Humans; Infusions, Intravenous; Pre-Eclampsia; Pregnancy

To investigate the possible role of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in the pathogenesis of pregnancy-induced hypertension (PIH).. A total of 110 normal pregnant women (in three trimesters, labour or postpartum) and 30 patients with PIH were studied by measuring plasma ET-1 and ANP levels by radioimmunoassay; 23 normal non-pregnant women were selected as controls.. Compared with normal non-pregnant women, plasma ET-1 levels were significantly decreased in normal pregnant women during all three trimesters. Plasma ET-1 level was significantly increased in the 2nd stage of labour, compared with that in the 3rd trimester. There were significant positive correlation between plasma ET-1 level and mean arterial pressure in normal non-pregnant women and normal pregnant women in all three trimesters. Compared with matched normal pregnant women, plasma ET-1 and ANP levels were significantly increased, while plasma ANP/ET-1 ratio was significantly decreased in PIH patients. Significant positive correlations existed between plasma ET-1 level and mean arterial pressure or the score index of the severity of PIH. After the treatment with magnesium sulfate infusion, plasma ET-1 and ANP levels were significantly decreased, but plasma ANP/ET-1 ratio was significantly increased in PIH patients.. Augmentation of ET-1 secretion and attenuation of ANP function may be responsible for the development of PIH. ET-1 secretion may be indirectly influenced by magnesium in PIH.

Topics: Adult; Atrial Natriuretic Factor; Endothelin-1; Female; Humans; Pre-Eclampsia; Pregnancy; Radioimmunoassay; Vasoconstriction

Atrial natriuretic peptide (ANP) is found to be elevated in preeclamptic patients despite the presence of hemodynamic characteristics such as vasoconstriction and hypovolemia. In this study, the effect on ANP secretion of plasma volume expansion with crystalloid solutions was investigated. Seven preeclamptic and seven normotensive pregnant women in their last trimester were compared. After basal ANP measurements, 0.9% Ringer's solution, 15 cm3/kg body weight was infused within 30 min to expand the plasma volume. Blood sampling was repeated after the infusion. Maternal blood volume expansion was calculated from the decrease in hematocrit. Plasma ANP levels were corrected according to the degree of volume expansion. Basal mean levels in both groups were not different. Although the postinfusion levels of ANP in normotensive pregnant women were similar to the basal levels (means +/- SE: 20.6 +/- 0.41 and 27.2 +/- 0.52 pg/ml, respectively, p = 0.10), the postinfusion ANP levels in preeclamptic women increased significantly (21.4 +/- 0.31 and 34.1 +/- 0.28 pg/ml, respectively, p = 0.01). Preeclampsia is associated with a greater increase in plasma ANP levels in response to volume expansion compared with normotensive pregnancy. The greater change in the right atrial pressure with volume expansion, due to decreased compliance of the capacitance vessels in preeclamptic subjects might explain the greater change in the plasma level of ANP.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Female; Humans; Plasma Volume; Pre-Eclampsia; Pregnancy; Reference Values

The decreased volume of maternal extracellular fluid in preeclamptics may result in a different rate of atrial natriuretic peptide secretion and thus affect its plasma levels. Our objectives were to determine whether there was a difference in plasma levels of atrial natriuretic peptide in the various hypertensive disorders of pregnancy. Forty-nine pregnant women in the third trimester of pregnancy were evaluated: 21 with preeclampsia, 17 with chronic hypertension during pregnancy and 11 normotensives. The atrial natriuretic peptide concentration was 13.9 +/- 5.9 pg/ml, 17.8 +/- 13.5 pg/ml and 16.7 +/- 7.4 pg/ml in the preeclamptics, chronic hypertensives and normotensives, respectively. The differences between the three groups were not statistically significant. Atrial natriuretic peptide plasma levels remained stable in the various hypertensive disorders of pregnancy.

Topics: Adult; Atrial Natriuretic Factor; Chronic Disease; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Third

Atriopeptin III (AP III) and its six analogues were synthesized by solid phase method and their diuretic and hypotensive activities were determined. Among these analogues, analogue [D-Ala-5, D-Arg-23] AP III was nearly 10 times as potent as AP III in diuretic activity while its hypotensive activity increased only 50% of that of AP III. Analogue des [Ser-15Gly-16Leu-17Gly-18Asn-20Ser-21] AP III was 15% as potent as AP III in diuretic activity, but it still maintained about 60% of the hypotensive activity of AP III. Meanwhile, we tried analogue [D-Ala-5, D-Agr-23] AP III for the treatment of hypertensive syndrome in pregnancy and obtained some good results.

Topics: Adult; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Diuretics; Female; Humans; Molecular Conformation; Peptide Fragments; Pre-Eclampsia; Pregnancy; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship

Topics: Atrial Natriuretic Factor; Blood Flow Velocity; Blood Pressure; Female; Humans; Placental Circulation; Pre-Eclampsia; Pregnancy; Pulsatile Flow

The pathophysiology of preeclampsia has not been fully clarified. A variety of factors have been implicated with this disease including vasoactive peptides and hormones during the last 20 years. Inadequate generation of atrial natriuretic peptide (ANP) has been one of the mechanisms discussed as to possibly contribute to the development of hypertension. In human pregnancy multiple studies of ANP-plasma-concentration in normal or hypertensive pregnancies showed conflicting results. The complexity of the clinical findings of hypertension in pregnancy makes it very difficult to carry out comparative clinical and biochemical studies in humans. In an animal experience genetic as environmental influences could be excluded. Therefore, the present study shows an experimental preeclampsia-like syndrome in the rat by reduction of the utero-placental flow. We observed a significant increase of plasma ANP in pregnant rats with experimentally induced hypertension. Furthermore, our results suggest that the ventricles could be an important source of ANP gene expression.

Topics: Animals; Atrial Natriuretic Factor; Female; Heart Atria; Heart Ventricles; Myocardium; Pre-Eclampsia; Pregnancy; Rats; Rats, Wistar; RNA, Messenger; Syndrome

Atrial natriuretic peptide (ANP) is a family of peptides secreted by the heart, affecting the cardiovascular, renal and endocrine systems. This study questions previous research findings regarding elevated ANP levels, despite vasoconstriction and hypovolemia, in preeclamptic patients.. Seventeen patients with preeclampsia, 5 with superimposed preeclampsia with chronic hypertension and 17 normotensive pregnant women were compared with respect to plasma ANP levels. Seventeen non-pregnant women were taken as the control group. All the women, except the ones with superimposed preeclampsia, were age matched and in their third trimester.. ANP levels in the non-pregnant women (6.9 +/- 0.7 pg/ml) were not different from those in the normotensive pregnant women (6.4 +/- 0.7 pg/ml). ANP levels were significantly higher in women with preeclampsia (10.8 +/- 1.8 pg/ml) or superimposed preeclampsia (9.7 +/- 1.4 pg/ml) than in normotensive pregnant women and normal non-pregnant women (P < 0.05). According to the literature, there is a volume depletion in preeclamptic women. However, this wasn't demonstrated in our study group.. ANP levels in preeclamptic women were found to be higher than those in normotensive pregnant women. The etiology still remains obscure.

Topics: Adolescent; Adult; Analysis of Variance; Atrial Natriuretic Factor; Blood Pressure; Case-Control Studies; Evaluation Studies as Topic; Female; Humans; Pre-Eclampsia; Pregnancy; Reference Values

Plasma levels of endothelin (ET) and atrial natriuretic peptide (ANP) were measured in 32 normal pregnant women and 26 patients with pregnancy induced hypertension (PIH). The correlation between ET and ANP were examined. This study indicated that the levels of ET and ANP in hypertensive pregnancy were higher than those of the normal pregnancy (P < 0.01). There was no correlation between ET and ANP in normal pregnancy (r = 0.18, P > 0.05), but significant inverse correlation in the patient with PIH (r = -0.57, P < 0.05). There findings suggested that ET may play an important role in the pathogenesis of PIH. An imbalance of increased amount of ET relative to deficient ANP may lead to PIH.

Topics: Adult; Atrial Natriuretic Factor; Endothelins; Female; Humans; Pre-Eclampsia; Pregnancy; Radioimmunoassay

Our purpose was to quantify fetoplacental vascular atrial natriuretic peptide receptor subtypes in human pregnancies complicated by intrauterine growth retardation or preeclampsia and to relate these parameters to the fetoplacental vascular impedance as assessed by Doppler velocimetry.. Guanylate cyclase-coupled and uncoupled receptors were quantified by radioligand-binding methods in membrane fractions prepared from primary and secondary stem villous vessels. Data for 16 abnormal pregnancies delivered preterm were compared with that for six gestationally matched preterm controls.. The number of guanylate cyclase-coupled receptors was significantly (p < 0.001) greater in pregnancies complicated by intrauterine growth retardation or preeclampsia irrespective of normal or abnormal umbilical artery Doppler blood flow velocity pattern. The number of guanylate cyclase-uncoupled receptors was unaltered.. Because fetal plasma atrial natriuretic peptide concentration is normal or elevated in intrauterine growth retardation and preeclampsia, these data suggest that atrial natriuretic peptide-mediated fetoplacental vasodilation is augmented in these disorders even in the presence of increased vascular resistance within the fetoplacental unit.

Topics: Atrial Natriuretic Factor; Binding, Competitive; Birth Weight; Blood Pressure; Delivery, Obstetric; Female; Fetal Growth Retardation; Gestational Age; Guanylate Cyclase; Humans; Infant, Newborn; Infant, Premature; Placenta; Pre-Eclampsia; Pregnancy; Radioligand Assay; Receptors, Atrial Natriuretic Factor; Regression Analysis; Rheology; Ultrasonography, Prenatal; Vascular Resistance

Brain natriuretic peptide (BNP) was increased in many hypertensive subjects. In this study, we have evaluated maternal, umbilical plasma and amniotic fluid BNP and atrial natriuretic peptide (ANP) in 19 normotensive pregnant women and in 35 preeclamptic patients. The maternal plasma and umbilical cord plasma ANP (p < 0.05) and BNP (p < 0.005) levels were significantly higher than those in normal pregnancy. There was no significant correlation among ANP level, BNP level, clinical symptoms and laboratory examinations. It is suggested that ANP and BNP may be rather a sequel to preeclamptic pathophysiological changes, and may not play an important role as the etiological factor of preeclampsia.

Topics: Amniotic Fluid; Atrial Natriuretic Factor; Female; Fetal Blood; Humans; Infant, Newborn; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Postpartum Period; Pre-Eclampsia; Pregnancy

To study the effects of low doses of the hormone atrial natriuretic peptide (ANP) on uteroplacental blood flow in patients with preeclampsia.. Eleven women with preeclampsia were infused intravenously with ANP (10 ng/kg/minute). Uteroplacental blood flow index was measured using dynamic placental scintigraphy with indium-113m. Regional blood flows were assessed by pulsed Doppler ultrasound and expressed as pulsatility index (PI). Hemodynamic measurements and blood sampling for peripheral venous plasma analysis of cyclic guanosine monophosphate (cGMP), an ANP second messenger, were performed before and after 30 minutes of infusion. Nonparametric statistics were used.. The uteroplacental blood flow index increased by 28% (-2 to 58%; mean and 95% confidence interval). The Doppler findings were unaffected. Mean arterial blood pressure decreased from 112 (108-117) to 108 (103-114) mmHg (P < .01). Cyclic GMP increased significantly from 9.2 (6.2-12.3) to 17.4 (12.3-22.6) nmol/L (P < .01). Subjects exhibiting a substantial increase in uteroplacental blood flow index (25% or more) demonstrated a significantly greater cGMP response (P < .01) than those who did not (6% or less increase).. A tendency to an increased uteroplacental blood flow index combined with minor blood pressure reduction after ANP infusion suggest the possibility of uteroplacental vasodilatation.

Topics: Adult; Atrial Natriuretic Factor; Blood Flow Velocity; Blood Pressure; Female; Guanosine Monophosphate; Humans; Indium Radioisotopes; Infusions, Intravenous; Maternal-Fetal Exchange; Placenta; Pre-Eclampsia; Pregnancy; Pulsatile Flow; Radionuclide Imaging; Regional Blood Flow; Ultrasonography, Prenatal; Uterus; Vasodilation

To compare normal pregnancy with pregnancy-induced hypertension (PIH)/preeclampsia with respect to the effects of acute volume expansion on plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP) and fetal-maternal circulation.. Observational study.. University hospital.. Fifteen women with PIH/preeclampsia and 15 healthy pregnant controls.. Before and after 30 minutes' infusion of a crystalloid solution (15 ml/kg), maternal venous blood was sampled for ANP and cGMP analysis and echocardiographic and Doppler investigations were performed.. Basal median (range) ANP and cGMP levels were significantly higher in the PIH/preeclampsia group compared to the controls: 6.5 (3.8-30.4) compared to 3.9 (2.0-6.7) pmol/l, p < 0.01 and 5.8 (2.4-11.6) compared to 4.0 (2.3-10.8) nmol/l, p < 0.05. The response to volume load was enhanced: 4.6 (-4.5-21.8) compared to 0.7 (-4.1-8.8), p < 0.05 and 2.9 (0.1-10.9) compared to 1.2 (-5.0-6.0), p < 0.05, respectively. Systemic vascular resistance was initially higher in the patient group, 22.3 (14.1-36.7) compared to 15.6 (10.0-25.5) peripheral resistance units, p < 0.01 but the response to volume load was similar in both groups (12-13% decrease). The pulsatility index of the uterine artery, 0.85 (0.46-1.38) compared to 0.72 (0.49-1.26) and umbilical artery 0.89 (0.66-1.57) compared to 0.97 (0.74-1.31) did not differ between the groups. Volume expansion did not affect any of these variables.. The pulsatility index of the uterine artery remained unaffected in both preeclamptic patients and healthy controls despite an increase of ANP and cGMP concentration and a systemic vasodilatation during acute volume expansion. This finding may indicate the absence of a vasodilation of the uteroplacental vascular bed.

Topics: Atrial Natriuretic Factor; Blood Circulation; Blood Volume; Cyclic GMP; Female; Fetal Blood; Humans; Hypertension, Renal; Maternal-Fetal Exchange; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Pulsatile Flow; Vascular Resistance

The hypothesis that preeclampsia may be associated with an increase in the response of the placental arteries to vasoconstrictors or a decrease in their response to vasodilators was tested.. Concentration-response curves to various agents were determined on helical strips of fetal placental arteries from normotensive (n = 33) and preeclamptic (n = 8) women to calculate the potencies and maximal effects of the agents.. Endothelin, prostaglandin F2 alpha, and serotonin caused concentration-dependent contractions; angiotensin II and norepinephrine produced little or no effects. The prostacyclin analog iloprost and atrial natriuretic factor, but not isoproterenol, relaxed placental arteries. Iloprost was more effective on preeclamptic than on normal arteries, but the effects of other agents on the two groups of arteries did not differ. Placental arteries exhibited spontaneous oscillations that were more marked in preeclamptic than in normal arteries and were inhibited by indomethacin.. Preeclampsia is not associated with an increase in the responses of fetal placental arteries to vasoconstrictors or a decrease in their response to vasodilators. However, placental arteries from preeclamptic subjects exhibit increased oscillations.

Topics: Adult; Angiotensin II; Arteries; Atrial Natriuretic Factor; Dinoprost; Endothelins; Female; Humans; Iloprost; Isoproterenol; Norepinephrine; Placenta; Pre-Eclampsia; Pregnancy; Serotonin; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

To study the relationship between somatostatin (SS), atrial natriuretic peptide (ANP), beta-endorphin (beta-EP), aldosterone (Aldo) and pregnancy induced hypertension (PIH), blood was collected from 69 cases, including non-pregnant women, normal pregnant women, patients with PIH and their newborns (umbilical arteries) and plasma levels of ANP, SS, beta-EP, Aldo were measured by radioimmunoassay. Results indicated that ANP, SS beta-EP and Aldo levels either during normal pregnancy or at delivery were significantly higher than those in non-pregnant women. ANP, SS and beta-EP levels in last trimester of patients with PIH, particular in severe cases, were significantly higher than those in normal pregnancy or moderate PIH whereas Aldo levels were lower in PIH when compared with normal pregnancy. A positive correlation between ANP, SS levels and the severity of PIH was observed. Levels of ANP, SS, beta-EP and Aldo in newborns were higher than those in mothers at delivery. Levels of ANP and SS in neonates born to mother of PIH were much higher, whereas beta-EP and Aldo were lower as compared with normal pregnancy. The conclusion is that high levels of ANP and Aldo during pregnancy may play an important role in stabilizing blood pressure and maintaining the balance of water and electrolyte. Therefore it could be used as an index for prediction of PIH.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; beta-Endorphin; Biomarkers; Female; Fetal Blood; Humans; Pre-Eclampsia; Pregnancy; Somatostatin

Highly active atrial natriuretic peptide III (haANP III) was administered for the treatment of heart failure due to pregnancy induced hypertension (PIH) in 7 patients with success. The heart failure was rapidly controlled within 24-48 hours with lowering of the blood pressure, disappearance of edema and urinary protein and alleviation of subjective symptoms. The plasma level of renin, angiotensin, aldosterone (RAA) and SOD all decreased. The results suggested that haANP III had the ability to facilitate the excretion of sodium and water, dilate the blood vessels and inhibit the action of RAA, and it could effectively reduce heart load and improve the cardiac function. Therefore, haANP III seemed to be an ideal new drug in treating heart failure in PIH, and it would have a wide scope for future development.

Topics: Adult; Atrial Natriuretic Factor; Female; Heart Failure; Humans; Peptide Fragments; Pre-Eclampsia; Pregnancy

This paper was written on the following base: 31 women with severe pregnancy induced hypertension (PIH) were chosen randomly as an observation group, 32 healthy and gestational age matched pregnant women with uneventful delivery were served as control group. Blood samples were collected from intervillous space of placenta and umbilical cord vein after delivery. The levels of LPO, SOD and atrial natriuretic peptide (ANP) were measured separately. From the placenta point of view, the pathogenic mechanism of PIH and the relation to the occurrence of intrauterine growth retardation (IUGR) were discussed. The results showed: the concentrations of LPO, SOD and ANP of placenta and umbilical cord vein were higher in the PIH group than that in the control group. The difference between 2 groups was statistically significant. A positive correlation between LPO and ANP was found both in PIH group and in control group (r = 0.641, P < 0.02). The birth weight of newborn was 2,174 +/- 142 g in PIH group and 3,460 +/- 187 g in control group. The difference between them was significant (P < 0.01). It suggested that the pathogenesis of PIH and the occurrence of IUGR might be closely related to the high concentration of LPO in placenta and umbilical cord vein.

Topics: Adult; Atrial Natriuretic Factor; Female; Fetal Blood; Fetal Growth Retardation; Humans; Infant, Newborn; Lipid Peroxides; Placenta; Pre-Eclampsia; Pregnancy; Superoxide Dismutase

A hypothesis is presented that high plasma concentration of alpha-human Atrial Natriuretic Peptide (ANP) might be responsible for hemoconcentration of preeclampsia (PE), mediated by increased diuresis and shift of fluid to the interstitium. ANP is known as a peptide regulating blood volume by diuresis and natriuresis, and perhaps through increased permeability in vessels. Moreover ANP is an antagonist to the renin-angiotensin-aldosterone (RAA) system, especially when this system is activated quantitatively as in pregnancy or qualitatively as in PE.

Topics: Atrial Natriuretic Factor; Blood Pressure; Capillary Permeability; Diuresis; Female; Humans; Models, Cardiovascular; Natriuresis; Plasma Volume; Pre-Eclampsia; Pregnancy; Renin-Angiotensin System

Plasma endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) concentrations were determined in 83 cases, including 30 cases of PIH and 30 normal pregnant women during their third trimester, and 23 non-pregnant women as controls.. compared to the non-pregnant women and normal pregnant women in their late pregnancy, the concentrations of plasma ET-1 and ANP were significantly increased in patients with PIH; after administration of magnesium sulfate infusion, the decrease of ET-1 and ANP concentrations was statistically significant in PIH cases, while there was no change in normal late pregnancy. In PIH patients, the score index of PIH had significant positive correlation with the level of plasma ET-1 (r = 0.717, P < 0.01). There were also positive correlations between the mean arterial pressure and the level of plasma ET-1 in PIH, normal pregnant and non-pregnant women (r = 0.613, P < 0.01; r = 0.441, P < 0.05; r = 0.586, P < 0.01). We failed to find any association between the concentrations of ET-1 and ANP in all 3 groups (r = 0.247, r = 0.384, r = -0.227; P > 0.05).. ET-1 acts as an important physioregulatory factor of blood pressure, and its increase may be responsible for the development of PIH, and may serve as an indicator of the severity of PIH.

Topics: Adult; Atrial Natriuretic Factor; Endothelins; Female; Humans; Magnesium Sulfate; Pre-Eclampsia; Pregnancy

From our perspective, Priscilla Kincaid-Smith's major achievement in the field of hypertension relates to the pathogenesis of vascular lesions. Our own studies of the hypertension of renal parenchymal disease have suggested a role for impairment of the cortisol-cortisone shuttle and decreased activity of the enzyme complex 11-beta-hydroxy-steroid dehydrogenase. We have defined the renal functional consequences of steroid-induced hypertension and shown that the rise in blood pressure produced by steroids with predominant glucocorticoid activity is not dependent on volume shifts or sodium status, although the magnitude of the rise is modulated by dietary sodium content. We have shown that normal pregnant women adapt readily to extremes of sodium intake while women with pre-eclampsia retain sodium, and have shown enhanced capillary permeability. Recent studies have defined an abnormal aldosterone:renin ratio, dopaminergic inhibition of aldosterone, elevations of plasma atrial natriuretic peptide and reduced urinary prostacyclin:thromboxane ratios in women with pre-eclampsia.

Topics: Adrenal Cortex Hormones; Atrial Natriuretic Factor; Australia; Female; History, 20th Century; Humans; Hypertension; Hypertension, Renal; Kidney; Nephrology; Pre-Eclampsia; Pregnancy; Renin-Angiotensin System

To investigate the involvement of brain natriuretic peptide in the circulation of pregnant women with pregnancy-induced hypertension.. We determined the plasma levels of brain and atrial natriuretic peptides in a cross-sectional study of 36 normal pregnant women and 17 women with pregnancy-induced hypertension.. During normal pregnancy, the plasma brain natriuretic peptide level was similar to that in nonpregnant women, but the plasma atrial natriuretic peptide level in the second trimester was significantly higher than that in nonpregnant women (P < .05). In women with severe pregnancy-induced hypertension, the plasma brain natriuretic peptide level was eight times higher than that in normal pregnant women in the third trimester; the plasma atrial natriuretic peptide level in the same patients was three times higher than that in normal pregnancy. The plasma brain natriuretic peptide level showed a positive correlation with the mean blood pressure (r = 0.62, P < .001).. The present findings suggest that brain natriuretic peptide is increased in the plasma of women with pregnancy-induced hypertension and that brain natriuretic peptide, in concert with atrial natriuretic peptide, participates in maintaining homeostasis of the maternal circulation.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Blood Urea Nitrogen; Cross-Sectional Studies; Female; Humans; Hypertension; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular

A new highly active atrial natriuretic peptide (haANP), synthesized by a solid phase technique, was given by intravenous infusion to 20 patients with severe pregnancy-induced hypertension (PIH) and the curative result of haANP was observed. Compared with basal values, supine systolic and diastolic BP was lowered significantly (P < 0.01), which may be related to the specific receptor of hANP and inhibition of renin-angiotensin-aldosterone system (RAAS). The haANP was found to possess significant effects of antispasm, detumescence and reducing proteinuria, probably by repairing mildly injured glomerulae, strong effects of diuresis and improving heart function with no side effects. Auto-antibody of hANP was found in patients with severe PIH, which affected the function of target cells of highly concentrated endogenous hANP. This auto-antibody might be one of the causes for PIH.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Infusions, Intravenous; Pre-Eclampsia; Pregnancy

The ANP (atrial natriuretic peptide) receptor binding site was studied in human placentas of normal and hypertensive pregnancy. The results showed there were specific high affinity ANP receptors in the nonbrush border (fetal side), and their affinity to ANP was higher than that in the microvillous membrane (meternal side). The ANP receptor affinity in the nonbrush border and microvillous membrane of normal pregnancy was higher than that of hypertensive pregnancy. Though the weight of placentas of hypertensive pregnancy was lower than that of normal pregnancy, high ANP concentrations in the placental tissues, umbilical and maternal blood were found in hypertensive pregnancy. It is believed that the distribution of ANP receptors in the placentas is related to hemodynamics, maternal exchange and fluid and electrolyte balance. The decrease of ANP receptors and lowering of affinity in hypertensive pregnancy may influence the the target cell effect of ANP, especially in the fetal side. This may be related to the pathogenesis of hypertensive pregnancy.

Topics: Atrial Natriuretic Factor; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

To study the antihypertensive effects of a new synthetic highly active atrial natriuretic peptide (haANP), the effects were observed in patients with moderate and severe pregnancy-induced hypertension (PIH). There were significant decreases in blood pressure (BP) for 10 min after haANP infusion (from 20.46 +/- 1.04/14.15 +/- 1.59 kPa to 18.17 +/- 0.60/11.08 +/- 1.36 kpa; P less than 0.05). 90 min after haANP infusion, BP decrease was the lowest (to 16.00 +/- 1.21/10.5 +/- 0.71 kPa; P less than 0.01), while plasma ANP levels increased 11 folds (from 47.5 +/- 5.5 ng/L to 525.4 +/- 15.6 ng/L). The effects continued for 300 minutes. Antihypertensive effects of magnesium sulphate were relatively relaxed (compared with those of haANP). The results showed strong and rapid antihypertensive effects of haANP. We found that mean RA and ALD levels were significantly decreased after haANP.

Topics: Adult; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Infusions, Intravenous; Pre-Eclampsia; Pregnancy; Renin-Angiotensin System

Topics: Aldosterone; Atrial Natriuretic Factor; Biomarkers; Catecholamines; Endothelium, Vascular; Female; Humans; Nitric Oxide; Pre-Eclampsia; Pregnancy; Prostaglandins; Renin-Angiotensin System

In this paper, patients with severe pregnancy induced hypertension (PIH) were treated with a highly active atrial natriuretic peptide (haANP). The results indicated that the effect of haANP in decreasing blood pressure (BP), clearing proteinuria and detumescence was marked. Serum hSOD-1 concentrations after haANP infusion decreased significantly (P less than 0.01). This may be related to the amelioration of the disease. Serum hSOD-1 concentrations in normal pregnancy and mild, moderate PIH were higher than in the non-pregnant. Serum hSOD-1 concentration in severe PIH was highest. These findings suggested the presence of a defence mechanism in the body against oxidative damage on tissues. The pathogenesis of PIH may be associated with the defence effect of the hSOD-1, and defective free radicals. The initial results suggest that ANP may be related to hSOD-1 in normal pregnancy as well as in PIH.

Topics: Adult; Atrial Natriuretic Factor; Female; Free Radicals; Humans; Pre-Eclampsia; Pregnancy; Superoxide Dismutase

The purpose of this study was to determine if endothelin levels are elevated in women with preeclampsia and if these levels correlated with other laboratory features of disease severity.. Parameters were compared in four groups of women volunteers by means of analysis of variance: (1) 16 women with preeclamptic pregnancies, (2) 11 pregnant women without preeclampsia, of similar lengths of gestation, (3) six otherwise normal women with pregnancies at term or beyond (greater than 38 weeks), and (4) 22 normotensive young women.. Endothelin levels were elevated in women with preeclampsia as compared with those of gestation-matched pregnant and nonpregnant controls (22.6 +/- 2.0 vs 12.0 +/- 1.0 vs 10.4 +/- 1.3 pmol/L, p less than 0.005, preeclampsia vs controls) and also were increased in late gestation (17.7 +/- 2.0 pmol/L). Endothelin correlated positively with plasma levels of uric acid (r = 0.698, p less than 0.005) and inversely with creatinine clearance (r = -0.659, p less than 0.05).. Circulating endothelin levels are elevated in women with preeclampsia and correlate closely with serum uric acid levels and measures of renal dysfunction. These observations suggest that endothelin may contribute to renal vasoconstriction in preeclampsia.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Endothelins; Female; Humans; Kidney; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Renin; Uric Acid

Atrial natriuretic peptide (ANP) concentrations are typically elevated in hypervolemic states. However, ANP levels have been reported to be increased in the peripartum period in women with preeclampsia, a disorder characterized by central hypovolemia. We postulated that ANP levels are elevated in preeclamptic patients before clinically evident disease. ANP concentrations were determined in three groups: uncomplicated pregnancies, pregnancies complicated by preeclampsia, and non-pregnant reproductive-aged women. The former groups were matched for gestational age at plasma sampling and delivery. The plasma samples, obtained prospectively from each patient during the first, second, and third trimesters and within 72 h postpartum, were frozen before RIA. A significant gestational increase in ANP was noted in both groups of pregnant women, with third trimester levels exceeding first trimester levels (P less than 0.05). Consistent with previous reports, ANP levels were elevated in overtly preeclamptic patients vs. matched controls in the third trimester. The ANP concentration was also significantly increased during the second trimester in women destined to develop preeclampsia. Postpartum ANP values decreased in the preeclamptic group to approach the level in normal patients postpartum. Thus, it appears that the stimuli of ANP secretion differ in uncomplicated and preeclamptic patients. Moreover, an elevation of plasma ANP is detectable before the onset of clinical evidence of preeclampsia.

Topics: Atrial Natriuretic Factor; Blood Pressure; Endothelins; Female; Humans; Postpartum Period; Pre-Eclampsia; Pregnancy

Plasma atrial natriuretic peptide (ANP) and circulatory responses were studied during rapid plasma volume expansion with crystalloid solutions. Sixteen women with preeclampsia and 16 healthy controls in the third trimester were compared. Basal mean (+/- standard error of the mean) ANP levels were not significantly higher in the preeclamptics than in controls (13.6 +/- 3.5 versus 6.4 +/- 1.1 pmol/L; not significant), but the increment following volume expansion was more pronounced (12.9 +/- 2.6 versus 6.1 +/- 2.3 pmol/L; P less than .05). The mean plasma volume expansion was less in the preeclamptic group (6.1 +/- 0.8 versus 9.3 +/- 1.1%; P less than .05), reflecting a higher capillary permeability in this disease. Left ventricular posterior-wall thickness in diastole was increased in the preeclamptics under basal conditions as compared with the controls (9.8 +/- 0.3 versus 8.9 +/- 0.3 mm; P less than .05), as was the thickness of the interventricular septum in systole (14.3 +/- 0.5 versus 12.3 +/- 0.6 mm; P less than .05). Systemic vascular resistance was higher in the preeclamptic group (19.7 +/- 0.8 versus 15.1 +/- 1.1 peripheral resistance units; P less than .01). In the controls, cardiac output increased by 23 +/- 4% and systemic vascular resistance decreased by 17 +/- 3%. The preeclamptic women reacted in a similar way. Our results indicate that preeclampsia is associated with an enhanced ANP response despite a less pronounced increase in plasma volume during acute fluid challenge.

Topics: Adult; Atrial Natriuretic Factor; Cardiac Output; Female; Hemodynamics; Humans; Plasma Volume; Pre-Eclampsia; Pregnancy

Preeclampsia is characterized by enhanced pressor responsiveness to angiotensin II. This report summarizes studies by our laboratory to investigate possible roles for calcium, sodium, membrane pumps, and the vasoactive hormones, atrial natriuretic peptide (hANP) and endothelin, in modulating the change in vascular reactivity characteristic of preeclampsia. Urinary calcium excretion, 1 alpha-25(OH)2D3 levels, and serum free calcium levels were all decreased, whereas parathyroid hormone levels and intraplatelet calcium concentrations were increased in women with preeclampsia. Erythrocyte sodium content was elevated, while red blood cell membrane Na-K-ATPase activity was decreased in patients with severe disease. Preeclamptics also had elevated levels of hANP, which failed to increase further when saline was infused or when blood pressure was increased transiently with angiotensin II administration. Finally, endothelin levels that are reduced in normal gestation, were increased in preeclampsia. While the cause of increased vascular reactivity is still unclear, there appear to be changes in the intracellular cation environment, combined with loss of compensating mechanisms, both at the membrane and humoral level, as well as enhanced concentrations of a potent vasoconstrictor in blood; all which lead to increases in vasoreactivity and blood pressure in preeclampsia.

Topics: Atrial Natriuretic Factor; Blood Pressure; Calcium; Endothelins; Female; Humans; Pre-Eclampsia; Pregnancy; Sodium; Vasoconstriction

The influence of preeclampsia on the circulating concentrations of the 28-amino-acid carboxy terminus (C-terminus) (i.e., atrial natriuretic factor) and the amino terminus (N-terminus) of the 126-amino-acid atrial natriuretic factor prohormone (pro ANF) was studied in the third trimester with the use of three specific radioimmunoassays that recognize: (1) atrial natriuretic factor (i.e., amino acids 99 to 126), (2) the whole 98-amino-acid N-terminus, and (3) amino acids 31 to 67 from the midportion of the N-terminus of the prohormone. The C-terminus was significantly increased (p less than 0.001) in the third trimester in women with preeclampsia, the mean +/- SEM of 15 subjects was 150 +/- 7 pg/ml versus 89 +/- 7 pg/ml in the third trimester in 12 women during normal pregnancies and 65 +/- 2 pg/ml in 19 healthy nonpregnant women. The whole 98-amino-acid N-terminus, likewise, was significantly increased (p less than 0.001) in women with preeclampsia to 4706 +/- 629 pg/ml versus 2160 +/- 79 pg/ml in women in the third trimester of normal pregnancies and versus the circulating concentration of 1847 +/- 127 pg/ml in healthy nonpregnant women. ProANF 31 to 67 mean circulating concentration in preeclampsia was 4638 +/- 725 pg/ml, which was also significantly (p less than 0.001) increased compared with its mean circulating concentration in the third trimester of normal pregnancy of 1758 +/- 83 pg/ml or that in healthy nonpregnant women (1400 +/- 105 pg/ml). The circulating concentrations of both the N-terminus and C-terminus of the atrial natriuretic factor prohormone decreased within 24 hours after delivery in contrast to a normal pregnancy in which they both increase post partum. These results indicate a marked difference in the metabolism of both the N-terminus and the C-terminus of the atrial natriuretic factor prohormone in women with preeclampsia versus that in women with normal pregnancies or that in healthy nonpregnant women.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Female; Humans; Peptide Fragments; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Protein Precursors; Radioimmunoassay

Atrial natriuretic peptide (ANP) was measured in arterial and venous umbilical cord plasma at the time of delivery by cesarean section in pre-eclamptic (n = 7) and normal women (n = 6). In addition venous samples were obtained from pre-eclamptic (n = 7) and normal pregnant women (n = 7) near term. ANP plasma levels were higher in pregnant women with pre-eclampsia than in normal pregnant women (27.9 +/- 4.4 [mean +/- SEM] and 14.1 +/- 2.5 pmol l-1, respectively, P less than 0.05). Immediately after delivery plasma ANP in pre-eclamptic mothers was 66.7 +/- 12.8 pmol l-1 compared to 13.9 +/- 2.2 pmol l-1 in normal mothers (P less than 0.01). However, in the pre-eclamptic group the levels of ANP in arterial and venous umbilical cord plasma (19.5 +/- 4.2 and 16.7 +/- 4.3 pmol l-1, respectively) were significantly (P less than 0.01) lower than ANP levels in arterial and venous cord plasma (39.6 +/- 1.0 and 31.1 +/- 4.2 pmol l-1, respectively) from normal mothers. It is concluded that the increased ANP plasma level in pre-eclamptic women originates from a maternal source. In addition, since the ANP level is lower in cord plasma than in maternal plasma in pre-eclampsia, feto-placental volume homeostasis may also be changed in pre-eclampsia.

Topics: Adult; Atrial Natriuretic Factor; Cesarean Section; Female; Fetal Blood; Humans; Labor, Obstetric; Maternal-Fetal Exchange; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third

The concentration of human serum superoxide dismutase-1 (hSOD-1) containing copper and zinc ions were measured by radioimmunoassay healthy nonpregnant women, 15 normal pregnant women, 15 patients with mild to moderate hypertension (MMHSP) and 15 with severe hypertensive syndrome of pregnancy (SHSP). The mean serum hSOD-1 concentration in nonpregnant women was 148.84 +/- 60.53 (x +/- s) micrograms/L; while in the other 3 groups it was 394.19 +/- 122.21 micrograms/L, 377.12 +/- 173.45 micrograms/L and 581.15 +/- 118.50 micrograms/L. The results suggest that harmful free radicals increase gradually and a strong body defence system against oxidation damage of tissue cells is produced in the course of normal pregnancy and MMHSP. With cardionatrin treatment serum hSOD-1 concentrations of patients ameliorated returned to the level of normal pregnancy. The results indicate that there is a positive correlation between cardionatrin and hSOD-1 levels (r = 0.569, P less than 0.05), and a physiological regulation of the defence system exists, which may be related to the white blood cells. Hence, hSOD-1 probably plays a significant role in defence during normal pregnancy and hypertensive syndrome of pregnancy (HSP).

Topics: Adult; Atrial Natriuretic Factor; Female; Humans; Peptide Fragments; Pre-Eclampsia; Pregnancy; Radioimmunoassay; Superoxide Dismutase

Plasma concentration of atrial natriuretic peptide (ANP) was determined in pregnant women with preeclampsia, in normal pregnant and in nonpregnant women by a specific radioimmunoassay. Results did not show important differences between nonpregnant controls and normal pregnant women, but a significant rise was seen in women with preeclampsia compared to nonpregnant controls. Marked interindividual variation was found in all three groups. The mechanism of ANP release may differ between those women with normal pregnancy and those with preeclampsia. It is unclear whether the increased level of ANP in preeclampsia is an effect or a cause of the disease.

Topics: Adult; Atrial Natriuretic Factor; Birth Weight; Female; Gestational Age; Hemodynamics; Humans; Menstruation; Postpartum Period; Pre-Eclampsia; Pregnancy; Radioimmunoassay

Topics: Atrial Natriuretic Factor; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Shock

Topics: Atrial Natriuretic Factor; Dioxolanes; Dipeptides; Female; Humans; Methacrylates; Pre-Eclampsia; Pregnancy; Thromboxane-A Synthase

Changes in plasmaconcentration of ANP in normal pregnancy and pregnancy complicated by pre-eclampsia were examined and compared to non-pregnant controls. The maternal plasma concentration increased gradually during normal pregnancy but values did not deviate significantly from non-pregnant women. A further increase was demonstrated post partum. In pre-eclampsia maternal plasma ANP levels increased significantly compared with normal gravida at the same gestational age and non-pregnant controls. After delivery ANP decreased significantly. Non correlation between ANP and aldosterone were found in either normal pregnancy nor pregnancy complicated by pre-eclampsia. It is not yet clear how important ANP is for the regulation of blood pressure and sodium and water balance during normal pregnancy and pregnancy complicated by pre-eclampsia.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third

Topics: Adult; Anemia, Hemolytic; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Liver Function Tests; Pre-Eclampsia; Pregnancy; Prospective Studies; Syndrome; Thrombocytopenia; Water-Electrolyte Balance

To clarify the possible role of elevated atrial natriuretic peptide (ANP) in the pathophysiology of preeclampsia, we measured ANP, renin activity (PRA), angiotensin II (Ang II), TXB2 (a stable metabolite of TXA2) and 6-keto-PGF1 alpha (a stable end product of PGI2) concentrations in the plasma of 19 normal pregnant women and 35 severe preeclamptic patients at term. Plasma ANP levels in the preeclamptic patients (n = 35, 71.5 +/- 3.8 pg/ml, mean +/- S.E.) and also umbilical plasma ANP (n = 35, 83.0 +/- 4.2 pg/ml) were significantly (p less than 0.01) higher than those of normal pregnant women plasma (n = 19, 58.7 +/- 3.7 pg/ml) and umbilical plasma (n = 19, 47.6 +/- 4.7 pg/ml). There was a significant (p less than 0.01) positive correlation between maternal ANP levels and fetal ANP levels (n = 54, r = 0.44). Plasma PRA and 6-keto-PGF1 alpha levels in preeclampsia were significantly (p less than 0.05) lower than those of normal pregnancy. The ratio of 6-keto-PGF1 alpha/TXB2 in preeclampsia was significantly (p less than 0.01) lower than that of normal pregnancy as we reported previously. There was no significant correlation between plasma ANP level and plasma PRA, Ang II, plasma TXB2 and 6-keto-PGF1 alpha concentrations. Moreover there was no significant correlation between plasma ANP level and the severity of preeclampsia. These data suggest the possibility of a transplacental crossing of ANP secreted by feto-placental unit, which might be, at least in part, responsible for the high ANP levels observed in preeclampsia. The ANP in preeclampsia is not related directly to hypertension, but it may play a substantial role in the regulation or normalization of blood volume and vascular reactivity.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Angiotensin II; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Epoprostenol; Female; Fetus; Humans; Pre-Eclampsia; Pregnancy; Radioimmunoassay; Renin; Thromboxane A2

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Female; Humans; Osmolar Concentration; Pre-Eclampsia; Pregnancy; Reference Values

A prospective longitudinal study of 25 pregnant women (30 pregnancies) with chronic hypertension, a group prone to development of preeclampsia, was conducted to explore the relationship between the renin-angiotensin-aldosterone system and the development of superimposed preeclampsia. In women with chronic hypertension in whom preeclampsia did not develop (17 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated, beginning in the first trimester and continuing throughout pregnancy as found previously in normotensive pregnant women (n = 58). Plasma estradiol and progesterone levels also increased progressively. In women with chronic hypertension in whom preeclampsia developed (13 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated in the first trimester as in the other groups. However, later in pregnancy significant differences were observed. Blood pressure began to rise in the second trimester. Initially the renin-angiotensin-aldosterone system remained stimulated, but in the early third trimester, when preeclampsia was diagnosed, plasma renin activity and urine aldosterone excretion decreased, and atrial natriuretic factor increased. These data provide information that may be useful in the recognition of superimposed preeclampsia, and in the investigation of its pathogenesis.

Topics: Adult; Analysis of Variance; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Chronic Disease; Estradiol; Female; Humans; Hypertension; Kidney; Longitudinal Studies; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Progesterone; Prospective Studies; Renin-Angiotensin System

The Atrial Natriuretic Factor discovered by De Bold in 1981, is currently being investigated by biochemists, physiologists and cardiologists. The physiological effects of this hormone closely resemble the normal changes occurring in pregnancy. Based on the experimental data published, the rise in the concentration of Atrial Natriuretic Factor in normal pregnancies may explain the physiological changes of pregnancy. It is postulated that the failure to induce a rise in the plasma concentration of Atrial Natriuretic Factor with its protective effects against the renin-angiotensin-aldosterone system will cause preeclampsia. A prospective study to compare serial Atrial Natriuretic Factor plasma concentrations with the pregnancy outcome from the point of view of preeclampsia is proposed to test this hypothesis.

Topics: Atrial Natriuretic Factor; Blood Volume; Female; Hemodynamics; Humans; Pre-Eclampsia; Pregnancy; Uterus

Atrial natriuretic factor may play a role in the regulation of blood pressure, renal function, and volume homeostasis in normal and pathologic states. Atrial natriuretic factor and plasma renin activity were measured by radioimmunoassay in pregnant women with normal blood pressure (n = 29), chronic hypertension (n = 17), and preeclampsia (n = 18) during the first, second, and third trimesters and in the postpartum period. Serial data were obtained in 11 patients. Nonpregnant age-matched women were used as controls (n = 14). In normal gestation and in chronic hypertension, atrial natriuretic factor levels were in the same range as that in the control group. Mean atrial natriuretic factor was significantly higher in the antepartum and postpartum periods in severe preeclampsia. There was an inverse relationship between atrial natriuretic factor and plasma renin activity in pregnancies complicated by chronic hypertension or preeclampsia. Although fluctuations in atrial natriuretic factor levels did not predict preeclampsia, atrial natriuretic factor did correlate with the severity of the disease.

Topics: Atrial Natriuretic Factor; Chronic Disease; Eclampsia; Female; Humans; Hypertension; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Renin

Little is known about atrial natriuretic peptide metabolism or secretion in the human fetus. The purpose of this study was to determine if both the placenta and umbilical vessels are possible sites of atrial natriuretic peptide metabolism and to evaluate the effects that labor, route of delivery, prolonged pregnancy, preeclampsia, and fetal distress have on umbilical arterial atrial natriuretic peptide levels. We found that plasma atrial natriuretic peptide levels in the umbilical artery are significantly greater than those in the vein (p less than 0.001). Umbilical arterial and umbilical venous atrial natriuretic peptide levels were higher in plasma samples collected immediately at delivery when compared with those obtained 10 minutes later (p less than 0.001). Umbilical arterial atrial natriuretic peptide levels were elevated in pregnancies complicated by preeclampsia and fetal distress (p less than 0.01). Labor, route of delivery, and prolonged pregnancy had no effect on umbilical arterial atrial natriuretic peptide levels. We propose that both the placenta and umbilical vessels contain atrial natriuretic peptide receptors that are involved in the clearance or metabolism of atrial natriuretic peptide. The increased umbilical arterial atrial natriuretic peptide levels present in preeclampsia and fetal distress may reflect an attempt by the fetus to regulate blood flow.

Topics: Atrial Natriuretic Factor; Cesarean Section; Female; Fetal Blood; Fetal Distress; Humans; Labor, Obstetric; Maternal-Fetal Exchange; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy, Prolonged; Umbilical Arteries; Umbilical Veins

There is a reduction in intravascular volume in patients with preeclampsia. Since the secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention, we sought to determine whether circulating maternal plasma atrial natriuretic factor concentrations were lower in patients with preeclampsia compared to normal pregnant women. The level of alpha-human atrial natriuretic factor was measured by a specific radioimmunoassay. Maternal venous concentrations of a alpha-human atrial natriuretic factor were higher in patients with severe preeclampsia (116.12 +/- 13.37 pg/ml) than in normal pregnant women (80.30 +/- 4.02 pg/ml). Umbilical artery alpha-human atrial natriuretic factor concentrations were higher in fetuses born to patients with severe preeclampsia (197.68 +/- 29.10 pg/ml) than normal control subjects (118.00 +/- 12.52 pg/ml). Umbilical artery alpha-human atrial natriuretic factor concentrations were higher than umbilical or maternal venous concentrations. In cases of severe preeclampsia, despite the presumed volume changes, maternal atrial natriuretic factor concentrations are higher than in normal pregnant women. The fetus appears to produce its own atrial natriuretic factor. Umbilical artery atrial natriuretic factor concentrations in fetuses born to preeclamptic mothers are higher than those seen in normal control subjects.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Birth Weight; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Parity; Pre-Eclampsia; Pregnancy; Radioimmunoassay

The possibility of evaluating the ratio between aldosterone and atrial natriuretic peptide (ANP) instead of the two hormones by themselves in studying sodium handling in normal pregnancy and in preeclampsia in the steady state and following albumin infusion was examined in this study. In 32 normal pregnancies monitored monthly, the highest aldosterone/ANP ratio was observed in the last weeks (28.7 +/- 12), and dropped in the first postpartum week (3.6 +/- 2.8), without changes in fractional excretion of sodium. In 18 preeclamptic patients, the ratio was significantly lower than in normal pregnancy at the same gestational ages, and it was coupled with absolute reduction in the sodium excretion. Among preeclamptic patients, a significant inverse correlation (P less than 0.025) was revealed between the ratio and sodium excretion. Natriuresis in response to acute volume expansion with albumin infusion occurred only in 50% of preeclamptic patients, and was associated with an ANP increase, an aldosterone decrease, and a further decrease in the ratio. A blunted natriuresis was observed in cases with a particularly low prealbumin value of this ratio. Furthermore, in preeclampsia, a particularly low ratio seemed to be typical of the patients who showed poorer placental flows and fetal outcomes. These results suggest that the balance between aldosterone and ANP may be a useful index in understanding sodium homeostasis in these settings.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Female; Humans; Natriuresis; Pre-Eclampsia; Pregnancy; Water-Electrolyte Balance

To assess the effect of endogenous human atrial natriuretic peptide on the vascular system in preeclampsia, the circadian variations of plasma human atrial natriuretic peptide, cyclic guanosine 3'5'-monophosphate, cyclic adenosine 3'5'-monophosphate, and blood pressure were measured. In severe preeclamptic women, the mean 24-hour values of human atrial natriuretic peptide and cyclic guanosine 3'5'-monophosphate rose significantly compared with those in normal nonpregnant and pregnant women. Also, in severe preeclamptic women, circadian variations of plasma atrial natriuretic peptide, cyclic guanosine 3'5'-monophosphate, and blood pressure confirmed the same circadian rhythm with acrophase during the middle of the night. Plasma cyclic adenosine 3'5'-monophosphate values did not differ significantly among the three groups and did not confirm a circadian rhythm. These results suggest that plasma human atrial natriuretic peptide may not strongly influence blood pressure, although it may induce the relaxation of vascular smooth muscles via the cyclic guanosine 3'5'-monophosphate system in preeclampsia.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Circadian Rhythm; Cyclic AMP; Cyclic GMP; Female; Humans; Pre-Eclampsia; Pregnancy

Particulate guanylate cyclase is stimulated by several hormones through receptor-dependent and by nitrosovasodilators through receptor-independent mechanisms. A subtype of atrial natriuretic peptide (ANP) receptors is coupled to guanylate cyclase. It has been shown that there is a down-regulation of the affinity of ANP receptors to alpha-hANP in placental plasma membranes obtained from severely toxemic patients. We have asked the question whether these changes are associated with a down-regulation of ANP-dependent guanylate cyclase activity. Guanylate cyclase was determined by in vitro experiments using a placental plasma membrane fraction obtained from normal and from severely toxemic patients. The presence of ANP-dependent placental guanylate cyclase activity was demonstrated both in normal and toxemic placentas. Although basal guanylate cyclase activity was not influenced by toxemia of pregnancy, there was a significant decrease in the maximum stimulation of this enzyme by alpha-hANP (104.81 +/- 12.02% (n = 4) vs 49.41 +/- 8.73% (n = 7) for normal and toxemics, respectively). Finally, stimulation by a nitrosovasodilator, sodium azide (NaN3), was also lower in toxemic placentas than in normal controls. These observations extend our previously reported results on placental ANP receptor function but also suggest the presence of a possibly receptor-independent decrease in guanylate cyclase activity in toxemic placentas.

Topics: Adult; Atrial Natriuretic Factor; Azides; Female; Guanylate Cyclase; Humans; Placenta; Pre-Eclampsia; Pregnancy; Sodium Azide

The influence of pregnancy on circadian variations of plasma atrial natriuretic peptide and aldosterone was studied. In those women with normal pregnancies, the mean 24-hour values of atrial natriuretic peptide and aldosterone increased, compared with the levels in normal nonpregnant subjects. In cases of severe preeclampsia, levels of atrial natriuretic peptide were significantly higher than in the other subjects, but aldosterone levels decreased to nearly those seen in the nonpregnant subjects. Atrial natriuretic peptide did not establish a rhythm in normal nonpregnant and pregnant subjects, but in the studies of aldosterone levels, a clear circadian rhythm was evident. In severe cases of preeclampsia, atrial natriuretic peptide established a circadian rhythm similar to that of blood pressure, and the circadian rhythm of aldosterone disappeared. The main characteristic of the rhythm in atrial natriuretic peptide and blood pressure in women showing preeclamptic signs is that the acrophase occurred at midnight. This evidence suggests that in women with symptoms of preeclampsia the load to the atria increases at midnight.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Circadian Rhythm; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third

Plasma immunoreactive atrial natriuretic factor 99-126 (ir ANF), plasma volume, plasma renin activity, and plasma aldosterone were measured during pregnancy in 14 normotensive nonpregnant women, 15 normotensive pregnant women, 35 patients with pregnancy-induced hypertension (PIH), and in ten patients with preeclampsia (PE). Repeated measurements were carried out 2 months after delivery in a subgroup of the same patients. The plasma levels of ANF were found to be higher in pregnant normotensive women than in nonpregnant normotensive women, but the decrease of plasma ANF 2 months after delivery was not significant on the basis of seven paired data, so that it cannot presently be stated with certainty that pregnancy per se stimulates ANF secretion. Still higher levels of ANF were found in PIH and, especially, in PE. A positive correlation was found in the pooled population of normotensive and hypertensive pregnant women between plasma ANF and mean arterial pressure. A greater decrease of plasma ANF was found after delivery in the hypertensive patients than in the normotensive controls. This excludes an absolute deficiency of ANF secretion in the pathogenesis of hypertension. These findings suggest a compensatory role of ANF in the prevention of blood pressure increase. Plasma renin activity (PRA) and plasma aldosterone concentrations were higher in normotensive pregnant women than in normotensive nonpregnant women. Compared to normal pregnancy, plasma volume was decreased in PIH (-17%) and in PE (-25%), whereas PRA was less increased in both groups and plasma aldosterone concentration was less increased only in the PE group. The simultaneous high levels of plasma ANF may explain this inappropriate hypostimulation of renin secretion by hypovolemia in these hypertensive states.

Topics: Adult; Analysis of Variance; Atrial Natriuretic Factor; Blood Pressure; Female; Follow-Up Studies; Humans; Hypertension; Plasma Volume; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Renin-Angiotensin System

Atrial natriuretic peptide (ANP) and arginine vasopressin concentrations were measured in 9 patients with pregnancy-induced hypertension. The results were compared to those found in 7 normal pregnant women matched for age, duration of pregnancy, and parity. Plasma ANP levels were significantly higher in the pregnancy-induced hypertension patients than in the control group. Plasma arginine vasopressin concentrations, however, were not significantly different in the two populations. The mechanism of the observed rise in ANP concentrations in the patients with pregnancy-induced hypertension is not known. However, it may be related to a rise in intra-atrial pressures secondary to hypertension, an increase in baroreceptor discharge as a result of hypertension, or, less likely, the ANP may be released from extracardiac sites.

Topics: Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Creatinine; Female; Humans; Pre-Eclampsia; Pregnancy; Proteinuria; Uric Acid

Topics: Atrial Natriuretic Factor; Female; Homeostasis; Humans; Hypertension; Hypothyroidism; Pre-Eclampsia; Pregnancy

The concentration of plasma immunoreactive atrial natriuretic peptide is positively associated with right atrial and pulmonary capillary wedge pressure, suggesting that blood volume and hence atrial pressure govern its release. Expansion of plasma volume is a central physiological adjustment in normal pregnancy. Conversely, pregnancies complicated by pre-eclampsia are associated with a reduction in plasma volume and central venous pressure. A study was therefore undertaken to test the hypothesis that plasma atrial natriuretic peptide concentrations are low in pre-eclampsia owing to deficient secretion. Concentrations of the peptide were measured by a specific radioimmunoassay. The mean plasma immunoreactive atrial natriuretic peptide concentration in healthy pregnant women (n = 22; third trimester) was higher (56 (1 SD 29) ng/l) than in 25 young, non-pregnant controls (37 (19) ng/l). Concentrations in patients suffering from mild pre-eclampsia (n = 9) were higher (127 (60) ng/l) than in normal pregnant women, and in patients with severe pre-eclampsia (n = 6) concentrations were higher still (392 (225) ng/l). Despite failure of plasma volume expansion and low central venous and pulmonary capillary wedge pressures in pre-eclampsia this condition is associated with greatly increased plasma concentrations of plasma immunoreactive atrial natriuretic peptide, which increase still further with the severity of the disease. These findings are clear evidence that atrial pressure may not be the principal determinant of the release of the natriuretic peptide in pre-eclampsia.

Topics: Adult; Atrial Natriuretic Factor; Female; Humans; Pre-Eclampsia; Pregnancy; Radioimmunoassay

Topics: Atrial Natriuretic Factor; Female; Humans; Kidney; Pre-Eclampsia; Pregnancy

In 12 healthy pregnant women, 14 women with mild or moderate late pregnancy gestosis (EPH) and in 12 non-pregnant women, the influence of head out water immersion (WI) on mean blood pressure (MAP), the renin-aldosterone system, vasopressin (AVP) and atrial natriuretic hormone (ANF) was examined. WI induced a prompt fall in MAP in all examined groups. This decrease of MAP was maximal after 1 h WI, showing a tendency to rise later on in pregnant women. Simultaneously a decrease of plasma renin activity (PRA), plasma aldosterone, AVP and an increase of ANF was noted. The WI induced endocrine reaction pattern was qualitatively similar, but quantitatively different in the examined groups. In contrast to the response of non-pregnant women, healthy pregnant women and women with EPH gestosis showed a significantly smaller increase in ANF secretion induced by WI. No correlation was found between PRA, plasma AVP, aldosterone and ANF respectively. In addition changes in PRA, aldosterone, AVP and ANF did not correlate with WI-induced changes in MAP. From data obtained in this paper it seems, that WI-induced MAP changes are not related significantly to changes of the above mentioned hormonal factors.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Hydrotherapy; Pre-Eclampsia; Pregnancy; Renin-Angiotensin System; Vasopressins

Changes in concentration of human atrial natriuretic peptide (hANP) in normal and toxaemic pregnancy were examined. The maternal plasma concentration of hANP increased gradually during normal pregnancy to a maximum of 20.0 +/- 2.4 pmol/l (mean +/- S.E.M.) after week 36 of pregnancy. From week 20, the plasma concentrations of hANP were significantly higher than those in non-pregnant women (9.3 +/- 2.0 pmol/l). In toxaemia with hypertension, maternal plasma hANP levels were increased after week 26 of pregnancy (37.7 +/- 6.0 pmol/l) compared with those in normal gravida at the same time (17.1 +/- 1.6 pmol/l). Maternal plasma hANP levels in toxaemia only with oedema were not different from those in normal gravida.

Topics: Adult; Atrial Natriuretic Factor; Edema; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy

Plasma cardionatrine was measured during pregnancy in 14 normotensive non pregnant women, 15 normotensive pregnant women, 35 pregnancy induced hypertension (PIH) and 10 preeclampsia (PE) and again 2 months after delivery in respectively 7, 15 and 7 cases together with plasma volume, PRA and plasma aldosterone. The plasma levels of cardionatrine are higher in pregnant normotensive women than in non pregnant normotensive women suggesting that pregnancy per se stimulates cardionatrine secretion. The higher levels of cardionatrine in PIH and specially in PE during pregnancy and the greater decrease of plasma cardionatrine after delivery in the hypertensive patients than in the normotensive controls exclude a deficiency of cardionatrine secretion in the pathogenesis of hypertension. These data rather suggest a compensatory role of cardionatrine in the prevention of blood pressure increase. Plasma volume was decreased in PIH (-17 p. 100) and in preeclampsia (-25 p. 100). The simultaneous high levels of cardionatrin may explain the inappropriate stimulation of the renin and aldosterone secretion in these hypovolemic hypertensive states.

Topics: Adult; Atrial Natriuretic Factor; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular

The increase of peripheral resistance in pregnancy induced hypertension (PIH) and in preeclampsia (PE) is not yet explained since previous studies have found that renin-angiotensin-aldosterone system is actually depressed, that adrenergic system is inconstantly stimulated and that vasodilating prostaglandins are inconstantly decreased. In order to get a better insight in the pathogenesis of PIH and PE, we have measured the 24 h urinary excretion of digoxin-like natriuretic factor (DLF) in 15 normotensive pregnant women (NP), in 29 women with PIH and in 6 women with PE under normal salt diet, without treatment. DLF have been measured by radio receptor binding assay. Normal values were established in 14 normotensive non pregnant (NNP). In NP, 24 h urinary excretion of DLF was significantly higher than in NNP (respectively 14.9 +/- 7.5 and 9.5 +/- 2.5 nmol/mmol of creatininuria, p less than 0.01). Comparatively to NP, 24 h urinary excretion of DLF was significantly higher in PIH (31.7 +/- 19 nmol/mmol of creatininuria) and in PE (40.7 +/- 16.3 nmol/mmol of creatininuria). In PIH and PE, there were simultaneously a decrease of plasma renin activity and plasma volume but no difference for plasma catecholamines.. 1. the production of DLF is increased by normal pregnancy; 2. it is increased in PIH and PE in comparison with NP and may explain the increase of peripheral resistance.

Topics: Adult; Atrial Natriuretic Factor; Blood Proteins; Cardenolides; Digoxin; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Saponins