Kynurenine Relaxes Arteries of Normotensive Women and Those With Preeclampsia.
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ABSTRACT:
SUBMITTER: Worton SA
PROVIDER: S-EPMC8154175 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Preeclampsia (PE) is characterized by the new onset of hypertension (HT) and proteinuria beyond the 20th week of gestation. We aimed to find the best predictor of PE and find out if it is different in women with or without HT. Consecutively attended pregnant women were recruited in the first trimester of pregnancy and followed-up. Laboratory and office and 24 h-ambulatory blood pressure (BP) data were collected. PE occurred in 6.25% of normotensives (n = 124). Both office mean BP and 24 h-systolic BP in the first trimester were higher in women with versus those without PE (p ≤ 0.001). In women with chronic hypertension (cHT), PE occurred in 55%; office SBP (p = 0.769) and 24 h-SBP (p = 0.589) were similar between those with and those without PE. Regarding biochemistry, in cHT, plasma urea and creatinine were higher in PE women than in those without cHT (p = 0.001 and p = 0.004 for the differences in both parameters). These differences were not observed in normotensives. In normotensives, mean BP was the best predictor of PE [ROC curve = 0.91 (95%CI 0.82-0.99)], best cut-off = 80.3 mmHg. In cHT, plasma urea and creatinine were the best predictors of PE, with ROC curves of 0.94 (95%CI 0.84-1.00) and 0.93 (95%CI 0.83-1.00), respectively. In the first trimester of pregnancy, the strongest predictor of PE in normotensive women is office mean BP, while in cHT, renal parameters are the strongest predictors. Otherwise, office BP is non-inferior to 24 h ambulatory BP to predict PE.
| S-EPMC9865932 | biostudies-literature
Project description:Background and purposeNuciferine, a constituent of lotus leaf, is an aromatic ring-containing alkaloid, with antioxidative properties. We hypothesize nuciferine might affect vascular reactivity. This study aimed at determining the effects of nuciferine on vasomotor tone and the underlying mechanismExperimental approachNuciferine-induced relaxations in rings of rat main mesenteric arteries were measured by wire myographs. Endothelial NOS (eNOS) was determined by immunoblotting. Intracellular NO production in HUVECs and Ca(2+) level in both HUVECs and vascular smooth muscle cells (VSMCs) from rat mesenteric arteries were assessed by fluorescence imaging.Key resultsNuciferine induced relaxations in arterial segments pre-contracted by KCl or phenylephrine. Nuciferine-elicited arterial relaxations were reduced by removal of endothelium or by pretreatment with the eNOS inhibitor L-NAME or the NO-sensitive guanylyl cyclase inhibitor ODQ. In HUVECs, the phosphorylation of eNOS at Ser(1177) and increase in cytosolic NO level induced by nuciferine were mediated by extracellular Ca(2+) influx. Under endothelium-free conditions, nuciferine attenuated CaCl2-induced contraction in Ca(2+)-free depolarizing medium. In the absence of extracellular calcium, nuciferine relieved the vasoconstriction induced by phenylephrine and the addition of CaCl2. Nuciferine also suppressed Ca(2+) influx in Ca(2+)-free K(+)-containing solution in VSMCs.Conclusions and implicationsNuciferine has a vasorelaxant effect via both endothelium-dependent and -independent mechanisms. These results suggest that nuciferine may have a therapeutic effect on vascular diseases associated with aberrant vasoconstriction.
| S-EPMC4667864 | biostudies-literature
Project description:Objective: To determine blood pressure (BP) patterns in the immediate postpartum period in preeclampsia with severe features (sPE) and normotensive pregnant women who had cesarean deliveries (CD).Study design: The BP levels of two groups comprising 50 sPE and 90 normotensive pregnant women who had CD were measured before delivery and on days 0-3 postpartum at four time points (05:00, 08:00, 14:00, and 22:00). Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PIGF) were measured in the maternal serum ≤48 h before delivery.Results: Antihypertensive therapy was administered to 98, 96, 82, 78, and 56% of sPE antepartum and on postpartum days 0-3, respectively. De novo postpartum hypertension (BP ≥ 140/90 mmHg) occurred in 24.4% (22/90) of the normotensive group but only one required antihypertensive therapy. The occurrence of de novo postpartum hypertension was associated with maternal weight before delivery ≥ 84.5 kg (relative risks (RR) 2.6, CI 95% 1.2-5.8, p = .017), and body mass index before delivery ≥ 33.3 kg/m2 (RR 2.9, CI 95% 1.3-6.4, p = .008). In sPE, the BP decreased between predelivery period and postpartum day 0. From days 1 to 3 postpartum, there was a continuous increase in the daily mean BPs in both groups, with average daily increments (systolic/diastolic) being 5.6/4.6 mmHg and 0.6/1.3 mmHg in the sPE and normotensive women, respectively. Patient's group and time had a significant effect on BP, p < .001. Overall, daily mean BPs were higher in the sPE than the normotensive group (p < .001). Perceived stress (p = .022), low birth weight (p = .002), 5 min Apgar score ≤ 6 (p < .001) were significantly higher in the sPE group. sFlt-1/PIGF ratio was high in the hypertensive groups: sPE versus normotensive group, p < .001; de novo postpartum hypertension versus normotensives group that remained normotensive, p = .102.Conclusion: Postpartum BP and antihypertensive requirements are important considerations in managing sPE and normotensive pregnancies. sPE is associated with increased maternal stress and poor perinatal outcomes.
| S-EPMC7193714 | biostudies-literature
Project description:The objective of this work was to compare Doppler flows pulsatility index (PI) and resistance indexes (RI) of uterine and internal iliac arteries during pregnancy in low risk women and in those with stage-1 essential hypertension. From January 2010 and December 2012, a longitudinal and prospective study was carried out in 103 singleton uneventful pregnancies (72 low-risk pregnancies and 31 with stage 1 essential hypertension)at the 1(st), 2(nd) and 3(rd) trimesters. Multiple linear regression models, fitted using generalized least squares and whose errors were allowed to be correlated and/or have unequal variances, were employed; a model for the relative differences of both arteries impedance was utilized. In both groups, uterine artery PI and RI exhibited a gestational age related decreasing trend whereas internal iliac artery PI and RI increased. The model testing the hemodynamic adaptation in women with and without hypertension showed similar trend. Irrespective of blood pressure conditions, the internal iliac artery resistance pattern contrasts with the capacitance pattern of its immediate pelvic division, suggesting a pregnancy-related regulatory mechanism in the pelvic circulation.
| S-EPMC3896929 | biostudies-other
Project description:The aim of the study was to assess if cardiovascular disease-associated microRNAs would be able to predict during the early stages of gestation (within 10 to 13 weeks) subsequent onset of hypertensive pregnancy-related complications: gestational hypertension (GH) or preeclampsia (PE). Secondly, the goal of the study was to assess if cardiovascular disease-associated microRNAs would be able to detect the presence of chronic hypertension in early pregnancies. The retrospective study was performed on whole peripheral blood samples collected from singleton Caucasian pregnancies within the period November 2012 to March 2020. The case control study, nested in a cohort, involved all women with chronic hypertension (n = 29), all normotensive women that later developed GH (n = 83) or PE with or without fetal growth restriction (FGR) (n = 66), and 80 controls selected on the base of equal sample storage time. Whole peripheral blood profiling was performed with the selection of 29 cardiovascular disease-associated microRNAs using real-time RT-PCR. Upregulation of miR-1-3p (51.72% at 10.0% FPR) was observed in patients with chronic hypertension only. Upregulation of miR-20a-5p (44.83% and 33.33% at 10.0% FPR) and miR-146a-5p (65.52% and 42.42% at 10.0% FPR) was observed in patients with chronic hypertension and normotensive women with later occurrence of PE. Upregulation of miR-181a-5p was detected in normotensive women subsequently developing GH (22.89% at 10.0% FPR) or PE (40.91% at 10.0% FPR). In a part of women with subsequent onset of PE, upregulation of miR-143-3p (24.24% at 10.0% FPR), miR-145-5p (21.21% at 10.0% FPR), and miR-574-3p (27.27% at 10.0% FPR) was also present. The combination of microRNA biomarkers (miR-20a-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, and miR-574-3p) can predict the later occurrence of PE in 48.48% of pregnancies at 10.0% FPR in early stages of gestation. The combination of upregulated microRNA biomarkers (miR-1-3p, miR-20a-5p, and miR-146a-5p) is able to identify 72.41% of pregnancies with chronic hypertension at 10.0% FPR in early stages of gestation. Cardiovascular disease-associated microRNAs represent promising biomarkers with very good diagnostical potential to be implemented into the current first trimester screening program to predict later occurrence of PE with or without FGR. The comparison of the predictive results of the routine first trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation and the first trimester screening for PE wo/w FGR using a panel of six cardiovascular disease-associated microRNAs only revealed that the detection rate of PE increased 1.45-fold (48.48% vs. 33.33%).
| S-EPMC8869238 | biostudies-literature
Project description:Background and purposeSmall (K(Ca) 2) and intermediate (K(Ca) 3.1) conductance calcium-activated potassium channels (K(Ca) ) may contribute to both epithelium- and endothelium-dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we investigated the expression of K(Ca) 2.3 and K(Ca) 3.1 channels, and hypothesized that activation of these channels would produce relaxation of human bronchioles and pulmonary arteries.Experimental approachChannel expression and functional studies were conducted in human isolated small pulmonary arteries and bronchioles. K(Ca) 2 and K(Ca) 3.1 currents were examined in human small airways epithelial (HSAEpi) cells by whole-cell patch clamp techniques.ResultsWhile K(Ca) 2.3 expression was similar, K(Ca) 3.1 protein was more highly expressed in pulmonary arteries than bronchioles. Immunoreactive K(Ca) 2.3 and K(Ca) 3.1 proteins were found in both endothelium and epithelium. K(Ca) currents were present in HSAEpi cells and sensitive to the K(Ca) 2.3 blocker UCL1684 and the K(Ca) 3.1 blocker TRAM-34. In pulmonary arteries contracted by U46619 and in bronchioles contracted by histamine, the K(Ca) 2.3/ K(Ca) 3.1 activator, NS309, induced concentration-dependent relaxations. NS309 was equally potent in relaxing pulmonary arteries, but less potent in bronchioles, than salbutamol. NS309 relaxations were blocked by the K(Ca) 2 channel blocker apamin, while the K(Ca) 3.1 channel blocker, charybdotoxin failed to reduce relaxation to NS309 (0.01-1 µM).Conclusions and implicationsK(Ca) 2.3 and K(Ca) 3.1 channels are expressed in the endothelium of human pulmonary arteries and epithelium of bronchioles. K(Ca) 2.3 channels contributed to endo- and epithelium-dependent relaxations suggesting that these channels are potential targets for treatment of pulmonary hypertension and chronic obstructive pulmonary disease.
| S-EPMC3448912 | biostudies-literature
Project description:The objective of the present study was to study whether pregnancy-related proteins are associated with preeclampsia.
2021-09-09 | PXD017862 | Pride
Project description:We report the results from RNA-seq analysis of perivascular adipose tissues (PVAT) collected from mesenteric arteries from Dahl S rats. Animals were on a control or a high fat diet for 24 weeks. At the moment of collection, rats fed high fat diet were hypertensive. In contrast, rats on the control diet were normotensive.
2021-01-23 | GSE165369 | GEO
Project description:INTRODUCTION:Transposition of the great arteries (TGA) is a cyanotic congenital heart defect that requires surgical correction, with the use of cardiopulmonary-bypass (CPB), usually within 3 weeks of life. The use of CPB in open heart surgery results in brain hypoperfusion and in a powerful systemic inflammatory response and oxidative stress. OBJECTIVE:We aimed to develop a novel untargeted metabolomics approach to detect early postoperative changes in metabolic profile following neonatal cardiac surgery. METHODS:We studied 14 TGA newborns with intact ventricular septum undergoing arterial switch operation with the use of CPB. Urine samples were collected preoperatively and at the end of the surgery and were analyzed using an untargeted metabolomics approach based on UHPLC-high resolution mass spectrometry. RESULTS:Since post surgery metabolic spectra were heavily contaminated by metabolites derived from administered drugs, we constructed a list of drugs used during surgery and their related metabolites retrieved from urine samples. This library was applied to our samples and 1255 drugs and drug metabolites were excluded from the analysis. Afterward, we detected over 39,000 unique compounds and 371 putatively annotated metabolites were different between pre and post-surgery samples. Among these metabolites, 13 were correctly annotated or identified. Metabolites linked to kynurenine pathway of tryptophan degradation displayed the highest fold change. CONCLUSIONS:This is the first report on metabolic response to cardiac surgery in TGA newborns. We developed an experimental design that allowed the identification of perturbed metabolic pathways and potential biomarkers of brain damage, limiting drugs interference in the analysis.
| S-EPMC6817811 | biostudies-literature
Project description:Preeclampsia is a pregnancy-specific multiorgan disorder in which impaired placental functioning and excessive oxidative stress play an important role. We previously showed distinct differences between cerebrospinal fluid proteins in patients with preeclampsia and normotensive pregnant women. An additional group of nonpregnant women was included to study the presence of pregnancy-related proteins in normotensive and preeclamptic pregnancies and whether pregnancy-related proteins were associated with preeclampsia. Cerebrospinal fluid samples were tryptically digested and subsequently measured with a nano-LC-tribrid Orbitrap mass spectrometry system. Proteins were identified by shotgun proteomic analysis based on a data-dependent acquisition method. Proteins identified in preeclampsia, normotensive pregnant controls, and nonpregnant groups were compared to the Progenesis method according to the criteria as previously described and with a secondary analysis using a Scaffold method including Benjamini-Hochberg correction for multiple testing. For preeclampsia, the Progenesis and the Scaffold method together identified 15 (eight proteins for both analyses with one overlap) proteins that were significantly different compared to normotensive control pregnancies. Three of these 15 proteins, which were elevated in cerebrospinal fluid of preeclamptic women, were described to be pregnancy proteins with a calcium-binding function. Using two analysis methods (Progenesis and Scaffold), four out of 15 differential proteins were associated with pregnancy, as described in the literature. Three out of the four pregnancy-related proteins were elevated in preeclampsia. Furthermore, the contribution of elevated (n = 4/15) and downregulated (n = 2/15) calcium-binding proteins in preeclampsia is remarkably high (40%) and needs to be elucidated further.
| S-EPMC7758887 | biostudies-literature