Stroke was regarded as a severe disorder with high morbidity and high mortality worldwide, ischemic stroke (IS) accounts for 85 to 90 % of new increased stroke cases. Partial mechanisms were elucidated by genetic factors including genomic instability such as single nucleotide polymorphism (SNP). Previous reports demonstrated that inflammation was involved in IS, NLRP3 [nucleotide-binding domain (NOD)-like receptor protein 3], acting as a specific inflammatory gene, however, its function and influence on IS was not well clarified. In this study, a case-control study including 1102 IS patients and 1610 healthy controls was conducted to investigate the association between IS susceptibility with a SNP (rs10754558) in 3'UTR of NLRP3. Logistic regression analysis showed that the heterozygote and the homozygote GG confer a significantly increased risk of CRC after controlling for other covariates (adjusted OR = 1.52, 95 % C.I. 1.19-1.97, P = 0.002; adjusted OR = 2.22, 95 % C.I. 2.18-3.67, P< 0.001, respectively). Carriage of G allele was associated with a greatly increased risk of developing the disease (OR = 1.69, 95 % C.I. 1.31-1.83, P < 0.001). Stratification analysis found that hypertension had interaction with rs10754558 to modulate IS risk. Further in vitro assay revealed that rs10754558 can affect mRNA level of NLRP3, suggesting its possible functional significance. Our data suggested that genetic polymorphisms in NLRP3 may influence IS risk in Chinese population. Replication of our studies in other populations and further functional studies are required for complete comprehension of the roles of NLRP3 polymorphisms in IS risk.

The renin–angiotensin system (RAS) has an important role in cardiovascular homeostasis. This study determined the influence of water deprivation during pregnancy on the development of the RAS in rats, and examined blood pressure (BP) in the adolescent offspring. Pregnant rats were water deprived for 3 days at late gestation, and we examined fetal cardiac ultrastructure, as well as heart angiotensin (Ang) II receptor protein and mRNA, liver angiotensinogen and plasma Ang II concentrations. We also tested cardiovascular responses to i.v. Ang II in the young offspring. In utero exposure to maternal water deprivation significantly decreased fetal body and heart weight, and increased fetal plasma sodium and osmolality. Fetal liver angiotensinogen mRNA, plasma Ang I and Ang II concentrations were also increased. Although fetal AT1a and AT1b receptor mRNA and AT1 protein were not changed, AT2 receptor mRNA and protein levels in the heart were significantly increased following maternal dehydration. Prenatal exposure to maternal water deprivation had no effect on baseline BP; however, it significantly increased BP in response to i.v. Ang II infusion, and decreased baroreflex sensitivity in the offspring. In addition, the heart AT2 receptor mRNA and protein were higher in the offspring exposed to prenatal dehydration. The results of this study demonstrate that prenatal dehydration affected the RAS development associated with an Ang II-increased BP in fetal origin.

Objective Central renin–angiotensin system (RAS) plays an important role in regulating body fluid balance. The present study determined the effect of maternal dehydration on brain expression levels of angiotensinogen, angiotensin II receptor subtypes, and dipsogenic responses in offspring. Methods Pregnant rats were deprived of water during late gestation. Expressions of brain angiotensinogen, angiotensin II receptors, and dipsogenic responses were determined. Results Maternal water deprivation significantly decreased fetal body and brain weight, and body and tail length. Fetal plasma sodium, osmolality, and hematocrit were increased. Both AT1R and AT2R protein abundance was significantly increased in the fetal brain, associating with increased mRNA levels of AT1aR and AT2R. Additionally, angiotensinogen mRNA was increased. In adult offspring, prenatal dehydration resulted in significant increases in AT1R protein and AT1aR mRNA, as well as angiotensinogen mRNA in the forebrain in both males and females. In contrast, AT2R mRNA and protein were increased only in males. Prenatal dehydration resulted in a significant increase in intracerebroventricular angiotensin II-induced water intake in male, but not female, offspring. Conclusion The results provided new information that antenatal water deprivation induces a reprogramming of brain RAS and Ang II receptor expression patterns and alters the central Ang II-mediated dipsogenic response in offspring in a sex-dependent manner.

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Aim Cholinergic regulation is important in the control of cardiovascular and endocrine responses. The mechanisms behind cardiovascular responses induced by cholinergic activation are explored by studying hormonal systems, including renin-angiotensin and vasopressin (VP). Results In chronically prepared fetal sheep, intravenous infusion of the cholinergic agonist carbachol increased fetal systolic, diastolic, and mean arterial pressure accompanied with bradycardia at near-term. Although intravenous administration of carbachol had no effect on plasma VP concentrations, this agonist increased angiotensin I and angiotensin II levels in fetal plasma. Fetal blood values, including sodium, osmolality, nitric oxide, hemoglobin, and hematocrit were unchanged by intravenous carbachol. Conclusion Cholinergic activation by carbachol controls fetal blood pressure and heart rate in utero. An over-activated fetal renin-angiotensin-system (RAS) is associated with changes in vascular pressure following intravenous administration of carbachol, indicating that the cholinergic stimulation-mediated hormonal mechanism in the fetus might play a critical role in the regulation of cardiovascular homeostasis.

Background: High blood pressure during pregnancy has been suggested to be associated with adverse birth outcomes (ABO), but it is unclear how different blood pressure changes and the extent of the effect. Therefore, we aimed to investigate the association between blood pressure trajectories (systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP)) of pregnant women and ABO in a real-world study. Material and Methods: Leveraging 28,679 pregnant women and their fetuses from a register-based cohort from January 1, 2010, to December 31, 2019. Blood pressure trajectories were estimated by package "traj" in R software using real-world blood pressure data of routine antenatal care examinations. Logistic regression models were applied to examine the association between trajectories of different blood pressure components (SBP, DBP, MAP, and PP) during pregnancy and the risk of ABO. Results: Trajectories of all blood pressure components were identically labeled as lowstable, moderate-increasing, moderate-decreasing and high-stable. After adjusting for confounding factors, compared with pregnant women with the low-stable pattern, pregnant women with a high-stable or moderate-increasing pattern had a significantly increased risk of developing adverse birth outcomes. Pregnant women with a moderate-decreasing pattern had no significant increased risk of ABO but had a lower risk of adverse birth outcomes than those with a moderate-increasing pattern. The trajectories crossed at 17-20 weeks of gestation for all blood pressure components. Conclusion:Our study results indicated that reduction and maintenance of blood pressure to a low level of less than 110 mmHg for SBP and 65 mmHg for DBP after 20 weeks of gestation would benefit prevention of adverse birth outcomes, regardless of the level of blood pressure at early pregnancy.