Plasma eNOS Concentration in Healthy Pregnancy and in Hypertensive Disorders of Pregnancy: Evidence of Reduced Concentrations in Pre-Eclampsia from Two Independent Studies.

Hypertensive disorders of pregnancy (HDP), comprising gestational hypertension (GH) and pre-eclampsia (PE), are leading causes of maternal and perinatal morbidity and mortality. Both GH and PE are characterized by new-onset hypertension, but PE additionally includes proteinuria and/or end-organ damage. Impaired nitric oxide (NO) bioavailability may lead to endothelial dysfunction in GH and PE, and the primary source of vascular NO is endothelial NO synthase (eNOS).

NAMPT levels are inversely related to nitric oxide formation and positively related to soluble fms-like tyrosine kinase-1 levels in preeclampsia.

NAMPT is a biomarker for endothelial dysfunction, but its relationship with nitrite (marker of NO formation) and soluble fms-like tyrosine kinase-1 (sFLT-1) has not been previously evaluated in preeclampsia. Therefore, we measured plasma NAMPT and sFLT-1 levels using enzyme immunoassays and plasma nitrite concentrations using an ozone-based chemiluminescence assay. NAMPT was positively correlated to nitrite (r = 0.

Longitudinal assessment of maternal-fetal Doppler parameters and maternal plasma level of matrix metalloproteinases 2 and 9.

Objective: To assess the behavior as well as the comparison between maternal circulating level of biochemical markers (matrix metalloproteinases - MMP-9 and MMP-2) and maternal-fetal Doppler parameters in all three trimesters of pregnancy.

Methods: We performed a prospective longitudinal study with 33 healthy pregnant women in three periods of pregnancy: A1 (12w0-14w6d), A2 (22w0d-24w6d) and A3 (34w0d and 36w6d). The following maternal Doppler parameters were assessed: mean pulsatility index (PI) uterine artery, resistance index (RI) umbilical artery and RI middle cerebral artery.

Assessment of nitrite oxide and maternal-fetal Doppler parameters during pregnancy.

Objective: The objective was to evaluate and compare the whole blood nitrite concentration in the three trimesters of pregnancy. Additionally, we investigate whether there is any relation between nitrite concentrations and Doppler ultrasound analysis of some maternal and fetal vessels.

Methods: Thirty-three healthy pregnant women were examined at the first (11-14 weeks), second (20-24 weeks) and third trimester (34-36 weeks) of pregnancy.

Positive correlations between circulating adiponectin and MMP2 in preeclampsia pregnant.

Objective: The aims of the present study were to compare plasma concentrations of the adiponectin, leptin, metalloproteinases (MMP9 and MMP2) and its tissue inhibitors (TIMP1 and TIMP2) in preeclamptic (PE) and healthy pregnant (HP) groups and correlate them.

Methods: A total of 105 pregnant women with pre-pregnancy body mass index (BMI) values ⩽ 30 kg/m(2) were enrolled for this study (59 PE and 46 HP). Biomarkers were measured using ELISAs.

Antihypertensive therapy in preeclampsia is not modulated by VEGF polymorphisms.

Introduction: Vascular endothelial growth factor (VEGF) is relevant for healthy pregnancy, and abnormalities in VEGF functions have been associated with hypertensive disorders of pregnancy. Our group recently demonstrated that VEGF genetic polymorphisms affect the susceptibility to preeclampsia (PE).

Objective: Therefore, in this study our aim is to examine whether VEGF polymorphisms affect the antihypertensive responses in women with PE.

Correlations between circulating levels of adipokines and anti-angiogenic factors in women with BMI <30 and a late-onset preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disease, directly related to high rates of maternal-fetal morbidity and mortality worldwide. Upregulation of anti-angiogenic factors (soluble fms-like tyrosine kinase-1; sFLT-1 and soluble endoglin; sENG) have been suggested to trigger the maternal endothelial dysfunction observed in PE. Studies focusing on the role of adiponectin and leptin, in normal pregnancy as well as in complicated pregnancies, have revelated interesting findings due to the vascular actions of such adipokines.

Antihypertensive effects of inducible nitric oxide synthase inhibition in experimental pre-eclampsia.

Upregulation of inducible nitric oxide synthase (iNOS) has been reported in both experimental and clinical hypertension. However, although pro-inflammatory cytokines that up-regulate iNOS contribute to pre-eclampsia, no previous study has tested the hypothesis that a selective iNOS inhibitor (1400 W) could exert antihypertensive effects associated with decreased iNOS expression and nitrosative stress in pre-eclampsia. This study examined the effects of 1400 W in the reduced uteroplacental perfusion pressure (RUPP) placental ischaemia animal model and in normal pregnant rats.

Relationship between adiponectin and nitrite in healthy and preeclampsia pregnancies.

Background: Controversial results have been reported regarding plasma adiponectin levels in preeclampsia (PE) compared to healthy pregnancies (HP). Adiponectin activates eNOS, increasing the levels of the vasodilator nitric oxide (NO). PE reduces the levels of nitrite (an NO marker) and induces higher levels of ADMA (an endogenous eNOS inhibitor) compared to HP.

Matrix metalloproteinases as drug targets in preeclampsia.

Preeclampsia is an important syndrome complicating pregnancy. While the pathogenesis of preeclampsia is not entirely known, poor placental perfusion leading to widespread maternal endothelial dysfunction is accepted as a major mechanism. It has been suggested that altered placental expression of matrix metalloproteinases (MMPs) may cause shallow cytotrophoblastic invasion and incomplete remodeling of the spiral arteries.

eNOS tag SNP haplotypes in hypertensive disorders of pregnancy.

Haplotypes formed by polymorphisms (T-786C, rs2070744; a variable number of tandem repeats in intron 4, and Glu298Asp, rs1799983) of the eNOS gene were associated previously with gestational hypertension (GH) and preeclampsia (PE). However, no study has explored the Tag SNPs rs743506 and rs7830 in these disorders. The aim of the current study was to compare the distribution of the genotypes and haplotypes formed by the five eNOS polymorphisms mentioned among healthy pregnant (HP, n=122), GH (n=138), and PE (n=157).

Effects of matrix metalloproteinase (MMP)-2 polymorphisms on responsiveness to antihypertensive therapy of women with hypertensive disorders of pregnancy.

Imbalanced matrix metalloproteinase (MMP) expression, including MMP-2, has been demonstrated in pre-eclampsia. However, little is known about the effect of polymorphisms in MMP-2 gene on hypertensive disorders of pregnancy. We examined whether two functional MMP-2 polymorphisms (g.

Polymorphisms and haplotypes in candidate genes related to angiogenesis and endothelial dysfunction in preeclampsia.

Valenzuela and colleagues have recently reviewed some polymorphisms in important candidate genes involved in different pathogenic mechanisms related to preeclampsia (PE) and concluded that various studies in different populations have identified maternal polymorphisms associated with PE. However, we would like to contribute to some studies regarding candidate genes related to angiogenesis and endothelial dysfunction in PE performed in the Brazilian population. Specifically, genotypes and haplotypes formed by polymorphisms of VEGF, eNOS and MMP-9, along with an example of the interaction among these genes in the prediction of PE.

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy.

We examined whether two functional polymorphisms (g.-1306C>T and g.-735C>T) in matrix metalloproteinase (MMP)-2 gene are associated with preeclampsia (PE) or gestational hypertension (GH), and whether they modify MMP-2 or tissue inhibitor of metalloproteinase (TIMP)-2 plasma concentrations in these hypertensive disorders of pregnancy.

Antihypertensive and antioxidant effects of a single daily dose of sodium nitrite in a model of renovascular hypertension.

Dietary nitrite and nitrate have been reported as alternative sources of nitric oxide (NO). In this regard, we reported previously that sodium nitrite added to drinking water was able to exert antihypertensive effects in an experimental model of hypertension in a dose-dependent manner. Taking into consideration that nitrite is continuously converted to nitrate in the bloodstream, here we expanded our previous report and evaluate whether a single daily dose of sodium nitrite could exert antihypertensive effects in 2 kidney-1 clip (2K1C) hypertensive rats.

Alterations in cyclic GMP levels in preeclampsia may reflect increased B-type natriuretic peptide levels and not impaired nitric oxide activity.

Objectives: We compared nitrite, B-type natriuretic peptide (BNP), and cGMP levels in preeclamptic with those found in healthy pregnant.

Methods: We studied 21 healthy pregnant and 27 preeclamptic. Plasma cGMP and BNP levels were determined by ELISA.

Antihypertensive effects exerted by enalapril in mild to moderate hypertension are not associated with changes in the circulating levels of nitric oxide-related markers.

Purpose: The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are explained, at least in part, by enhanced bradykinin-dependent nitric oxide (NO) formation and decreased angiotensin II-induced oxidative stress and vasoconstriction. We examined for the first time whether treatment with enalapril increases the plasma levels of markers of NO formation and decreases oxidative stress in mild to moderate hypertensive patients.

Methods: Eighteen untreated hypertensive patients were treated with enalapril 10 mg/day (n=10) or 20 mg/day (n=8) for 60 days.

Interethnic differences in ADMA concentrations and negative association with nitric oxide formation in preeclampsia.

Background: Recent studies have suggested that impaired nitric oxide (NO) formation in preeclampsia may result from increased concentrations of an endogenous NO synthase inhibitor, the asymmetric dimethylarginine (ADMA). However, no previous study has examined whether a negative association exists between ADMA and nitrite concentrations in preeclampsia. Moreover, no previous study has compared ADMA and nitrite levels in black and white preeclamptic pregnant women.

Increased circulating cell-free hemoglobin levels reduce nitric oxide bioavailability in preeclampsia.

Contrasting with increased nitric oxide (NO) formation during healthy pregnancy, reduced NO bioavailability plays a role in preeclampsia. However, no study has examined whether increased NO consumption by enhanced circulating levels of cell-free hemoglobin plays a role in preeclampsia. We studied 82 pregnant women (38 healthy pregnant and 44 with preeclampsia).

Effects of eNOS polymorphisms on nitric oxide formation in healthy pregnancy and in pre-eclampsia.

Pre-eclampsia (PE) is associated with decreased nitric oxide (NO) formation. However, no previous study has examined whether genetic variations in the endothelial NO synthase (eNOS) affect this alteration. We hypothesized that PE decreases NO formation depending on eNOS polymorphisms.

Matrix metalloproteinase (MMP)-9 genotypes and haplotypes in preeclampsia and gestational hypertension.

Background: Abnormal production of matrix metalloproteinases (MMPs), especially MMP-9, may play a role in hypertensive disorders of pregnancy. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 gene, which are known to change MMP-9 expression. We examined whether 2 MMP-9 polymorphisms (C(-1562)T and (CA)n) and haplotypes are associated with preeclampsia and/or gestational hypertension.

Evidence for the involvement of matrix metalloproteinases in the cardiovascular effects produced by nicotine.

Nicotine plays a role in smoking-associated cardiovascular diseases, and may upregulate matrix metalloproteinase (MMP)-2 and MMP-9. We examined whether nicotine induces the release of MMP-2 and MMP-9 by rat smooth muscle cells (SMC), and whether doxycycline (non-selective MMP inhibitor) inhibits the vascular effects produced by nicotine. SMC were incubated with nicotine 0, 50, and 150 nM for 48 h.

Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension.

Vascular endothelial growth factor (VEGF) is relevant for normal pregnancy, and abnormalities in VEGF functions are associated with hypertensive disorders of pregnancy. Because there are few studies on how VEGF genetic polymorphisms affect susceptibility to pre-eclampsia (PE), and no studies on how they affect susceptibility to gestational hypertension (GH), we compared VEGF genotype and haplotype distributions in normotensive and hypertensive pregnancies. Genotypes and haplotypes for VEGF polymorphisms (C-2578A, G-1154A and G-634C) were determined in 303 pregnant women (108 healthy pregnant, HP; 101 with GH and 94 with PE).