scholarly journals The Effect of BML-111 in Preeclampsia Rat Model Induced by the Low Dose of Cadmium Chloride

2019 ◽  
Vol 09 (03) ◽  
pp. e201-e208 ◽  
Author(s):  
KeKe Zhang ◽  
Min Hu ◽  
Lin Zhang ◽  
Qiong Zhang ◽  
Yinping Huang

Aim This article determines the optimal time and dose of cadmium chloride (CdCl2) injected to pregnant rat to establish experimental preeclampsia (PE) model. In addition, the therapeutic potential of BML-111, a lipoxin A4 analogue, in the CdCl2-induced PE model was also evaluated. Methods Peritoneal injection of two dose of CdCl2 for successive 6 days was tested in the pregnant rats starting from various gestational days (GDs). During this process, the systolic blood pressure and the body weight of pregnant rats and neonatal rats were monitored. The pathological changes of the placenta and kidney were evaluated by hematoxylin and eosin staining. The phosphorylation of extracellular signal-regulated kinase 1/2 and signal transducer and activator of transcription 3 in the placentas was detected by Western blot, and the messenger ribonucleic acid expression of interleukin (IL)-6, tumor necrosis factor-α, and IL-10 in the placentas were detected by real-time polymerase chain reaction. BML-111 at the dose of 1 mg/kg/day was peritoneally injected into the rat after establishing the PE model to test its therapeutic potential. Results In the present study, we successfully established the PE model in pregnant rats by intraperitoneally injection of CdCl2 at the dose of 0.125 mg/kg/day from GD 9 to 14. We recapitulated multiple features of clinical PE in CdCl2-induced rat, including high blood pressure, renal dysfunction, and inflammatory response in placenta. Furthermore, treatment with BML-111 significantly relieved multiple features in our PE rat model. Conclusions BML-111 has a potential therapeutic effect in pregnant rats with CdCl2-induced PE, which appears to be mediated through inhibition of inflammatory processes in the placenta.

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaowen Jia ◽  
Rong Zhang ◽  
Jinzhu Guo ◽  
Hua Yue ◽  
Qiuxia Liu ◽  
...  

Background. Pregnancy-induced hypertension (PIH) remains a major cause of morbidity and mortality in pregnancy worldwide. This study was designed to study the blood pressure-lowering effect of resveratrol (RES) in a salt-induced hypertensive pregnant rat model. Methods. Forty female Sprague Dawley (SD) rats were randomized into 4 groups: Normal Preg (0.9% salt diet), Normal Preg + RES (0.9% salt diet plus daily oral RES for 4 weeks), Salt Preg (8% salt diet), and Salt Preg + RES (8% salt diet plus daily oral RES for 4 weeks). Noninvasive blood pressure was recorded on gestational days 7 and 14. On the gestational day 19, foetuses were weighed, and blood and urine samples were harvested for electrolytes and biochemical assays. Results. RES significantly reduced SBP, DBP, and MAP on gestational days 7 and 14 in the Salt Preg + RES group compared to the Salt Preg group (all P<0.05). Compared to the Salt Preg group, the foetal weight, serum NO level, urinary sodium, and 24 hour urine volume were significantly increased in the Salt Preg + RES group (all P<0.05). On the contrary, the levels of serum urea, serum creatinine, and urinary protein were significantly decreased in the Salt Preg + RES group compared to the Salt Preg group (all P<0.05). Conclusions. RES decreases blood pressure in a hypertensive pregnant rat model. Increasing sodium excretion and serum nitric oxide level might be, at least part of, the underlying mechanisms.


1992 ◽  
Vol 262 (6) ◽  
pp. R1100-R1105 ◽  
Author(s):  
T. Hines ◽  
W. M. Barron

We tested the hypothesis that augmented arterial baroreflex activity contributes to attenuation of pressor responses in intact pregnant animals by comparing changes in blood pressure and heart rate during infusions of angiotensin II, phenylephrine, and vasopressin in chronically instrumented pregnant and virgin rats approximately 5 wk after sinoaortic denervation (SAD) or sham surgery. Baseline mean arterial pressure was significantly lower in pregnant animals in both the sham-operated (pregnant 91.7 +/- 1.7 mmHg, virgin 103.7 +/- 2.5 mmHg) and SAD states (pregnant 107.3 +/- 4.0 mmHg, virgin 114.1 +/- 4.0 mmHg). Pressor responses to all three agents were significantly blunted in pregnant animals compared with similarly treated virgins, with the magnitude of attenuation similar in both sham and SAD states. Heart rate decreased similarly in reflex-intact pregnant and virgin animals during pressor infusions. These findings suggest that attenuated pressor responses in the pregnant rat are due primarily to mechanisms other than augmentation of arterial baroreflex activity and are consistent with a generalized reduction in vascular sensitivity during gestation.


2005 ◽  
Vol 288 (1) ◽  
pp. F221-F226 ◽  
Author(s):  
Yiqiang Zhou ◽  
Hsin-Hsin Chang ◽  
Juan Du ◽  
Cong-Yi Wang ◽  
Zheng Dong ◽  
...  

Epoxyeicosatrienoic acids (EETs), which belong to cytochrome P-450 (CYP)-derived eicosanoids, have been implicated to vasodilate renal arterioles, inhibit sodium transport in the nephron, and regulate blood pressure in several animal models. Because pregnancy is associated with changes of blood pressure, the aim of this study was to examine whether renal EET synthesis is altered and whether EETs are involved in blood pressure regulation during pregnancy in rats. Renal microsomal epoxygenase activity increased by 47, 97, and 63% on days 6, 12, and 19 of gestation, respectively. The elevation of epoxygenase activity during pregnancy was associated with an increase in CYP2C11, CYP2C23, and CYP2J2 protein expression on days 6, 12, and 19 of gestation. Moreover, immunohistochemical analysis showed that renal tubular CYP2C11, CYP2C23, and CYP2J2 expression was significantly increased in pregnant rats on days 6, 12, and 19 of gestation. Administration of 6-(2-propargyloxyphenyl)hexanoic acid (PPOH), a selective epoxygenase inhibitor, caused a dose-dependent inhibition of microsomal expoxygenase activity without a significant effect on ω-hydroxylase activity in female rats. Interestingly, administration of PPOH (20 mg·kg−1·day−1 for 4 days starting on day 15 of pregnancy) increased blood pressure by 21 mmHg and caused a significant decrease in the body weight of fetal pups (1.3 ± 0.08 g in control vs. 1.1 ± 0.06 g in PPOH). Moreover, PPOH treatment significantly decreased renal microsomal epoxygenase activity and the expression of CYP2C11, CYP2C23, and CYP2J in pregnant rats. This study demonstrates that EET synthesis in the kidney is elevated during pregnancy, and CYP2C11, 2C23, and CYP2J2 are responsible for the change of renal EET synthesis. The inhibition results demonstrate that the downregulation of renal epoxygenase activity by PPOH causes hypertension in pregnant rats. This study suggests that EETs may contribute to the control of blood pressure during pregnancy.


2016 ◽  
Vol 311 (6) ◽  
pp. R1068-R1075 ◽  
Author(s):  
Mais M. Aljunaidy ◽  
Jude S. Morton ◽  
Christy-Lynn Cooke ◽  
Sandra T. Davidge

Intrauterine growth restriction (IUGR) is a common pregnancy complication and is a leading cause of fetal morbidity and mortality. Placental hypoxia contributes to adverse fetal consequences, such as IUGR. Exposing pregnant rats to hypoxia can lead to IUGR; however, assessment of maternal vascular function in a rat model of hypoxia, and the mechanisms that may contribute to adverse pregnancy outcomes, has not been extensively studied. We hypothesized that exposing pregnant rats to hypoxia will affect maternal systemic vascular function and increase the uterine artery resistance index (RI), which will be associated with IUGR. To test this hypothesis, pregnant rats were kept in normoxia (21% O2) or hypoxia (11% O2) from gestational day (GD) 6 to 20. Maternal blood pressure, uteroplacental resistance index (RI) (ultrasound biomicroscopy), and vascular function (wire myography) were assessed in uterine and mesenteric arteries. Fetal weight was significantly reduced ( P < 0.001), while maternal blood pressure was increased ( P < 0.05) in rats exposed to hypoxia. Maternal vascular function was also affected after exposure to hypoxia, including impaired endothelium-dependent vasodilation responses to methacholine in isolated uterine arteries (pEC50 normoxia: 6.55 ± 0.23 vs. hypoxia: 5.02 ± 0.35, P < 0.01) and a reduced uterine artery RI in vivo (normoxia: 0.63 ± 0.04 vs. hypoxia: 0.53 ± 0.01, P < 0.05); associated with an increase in umbilical vein RI (normoxia: 0.35 ± 0.02 vs. hypoxia: 0.45 ± 0.04, P < 0.05). These data demonstrate maternal and fetal alterations in vascular function due to prenatal exposure to hypoxia. Further, although there was a compensatory reduction in uterine artery RI in the hypoxia groups, this was not sufficient to prevent IUGR.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mazhar Pasha ◽  
Amy L. Wooldridge ◽  
Raven Kirschenman ◽  
Floor Spaans ◽  
Sandra T. Davidge ◽  
...  

Advanced maternal age (≥35 years old) increases the risk of pregnancy complications such as preeclampsia and fetal growth restriction. We previously demonstrated vascular dysfunction and abnormal pregnancy outcomes in a rat model of advanced maternal age. However, vascular adaptations to pregnancy in aging were not studied. We hypothesize that advanced maternal age is associated with a more vasoconstrictive phenotype due to reduced nitric oxide (NO) and increased activity of matrix metalloproteinases (MMPs), contributing to impaired vascular adaptations to pregnancy. A rat model of advanced maternal age was used: young (4 months) and aged (9.5 months; ∼35 years in humans) non-pregnant and pregnant rats. On gestational day 20 (term = 22 days; non-pregnant rats were aged-matched), blood pressure and heart rate were measured (tail cuff plethysmography) and vascular function was assessed in mesenteric arteries (wire myography). Endothelium-dependent relaxation to methylcholine (MCh) was assessed in the presence/absence of nitric oxide synthase inhibitor (L-NAME), or inhibitors of endothelium-dependent hyperpolarization (EDH; apamin and TRAM-34). Vasoconstriction responses to big endothelin-1 (bigET-1), in the presence/absence of MMPs-inhibitor (GM6001) or endothelin converting enzyme (ECE-1) inhibitor (CGS35066), in addition, ET-1 responsiveness, were measured. Blood pressure was elevated only in aged non-pregnant rats (p &lt; 0.001) compared to all other groups. MCh responses were not different, however, L-NAME decreased maximum vasodilation in young (p &lt; 0.01) and aged pregnant rats (p &lt; 0.001), and decreased MCh sensitivity in young non-pregnant rats (p &lt; 0.01), without effects in aged non-pregnant rats. EDH contribution to relaxation was similar in young non-pregnant, and aged non-pregnant and pregnant rats, while EDH-mediated relaxation was absent in young pregnant rats (p &lt; 0.001). BigET-1 responses were enhanced in aged non-pregnant (p &lt; 0.01) and pregnant rats (p &lt; 0.05). No significant changes in bigET-1 conversion occurred in the presence of MMP-inhibitor, whereas ECE-1 inhibition reduced bigET-1 constriction in aged rats (p &lt; 0.01). No differences in ET-1 sensitivity were observed. In conclusion, contrary to our hypothesis, reduced blood pressure, and an increased EDH-dependent contribution to vasodilation suggest a compensatory mechanism that may reflect beneficial adaptations in these aged rats that were able to maintain pregnancy. These data increase our understanding of how the vascular adaptive pathways in pregnancy compensate for advanced maternal age.


1949 ◽  
Vol 89 (3) ◽  
pp. 287-293 ◽  
Author(s):  
Emily N. Loeb ◽  
Abbie I. Knowlton ◽  
Herbert C. Stoerk ◽  
Beatrice C. Seegal

1. Pregnancy enhances the susceptibility of the rat to intercurrent renal damage produced by anti-placenta serum. This is manifested by the development of renal hypertrophy and nephritis in a number of these animals. Both renal hypertrophy and nephritis are consistently intensified by the concomitant administration of DCA. 2. Hypertension develops in both pregnant and non-pregnant rats treated with the anti-placenta serum employed together with the daily administration of DCA. 3. Termination of pregnancy, in the face of continued DCA administration, fails to lower the blood pressure or to arrest the nephritic process.


2018 ◽  
Vol 32 (1) ◽  
pp. 30-42 ◽  
Author(s):  
Claudia Traunmüller ◽  
Kerstin Gaisbachgrabner ◽  
Helmut Karl Lackner ◽  
Andreas R. Schwerdtfeger

Abstract. In the present paper we investigate whether patients with a clinical diagnosis of burnout show physiological signs of burden across multiple physiological systems referred to as allostatic load (AL). Measures of the sympathetic-adrenergic-medullary (SAM) axis and the hypothalamic-pituitary-adrenal (HPA) axis were assessed. We examined patients who had been diagnosed with burnout by their physicians (n = 32) and were also identified as burnout patients based on their score in the Maslach Burnout Inventory-General Survey (MBI-GS) and compared them with a nonclinical control group (n = 19) with regard to indicators of allostatic load (i.e., ambulatory ECG, nocturnal urinary catecholamines, salivary morning cortisol secretion, blood pressure, and waist-to-hip ratio [WHR]). Contrary to expectations, a higher AL index suggesting elevated load in several of the parameters of the HPA and SAM axes was found in the control group but not in the burnout group. The control group showed higher norepinephrine values, higher blood pressure, higher WHR, higher sympathovagal balance, and lower percentage of cortisol increase within the first hour after awakening as compared to the patient group. Burnout was not associated with AL. Results seem to indicate a discrepancy between self-reported burnout symptoms and psychobiological load.


Author(s):  
Pramukti Dian Setianingrum ◽  
Farah Irmania Tsani

Backgroud: The World Health Organization (WHO) explained that the number of Hyperemesis Gravidarum cases reached 12.5% of the total number of pregnancies in the world and the results of the Demographic Survey conducted in 2007, stated that 26% of women with live births experienced complications. The results of the observations conducted at the Midwife Supriyati Clinic found that pregnant women with hyperemesis gravidarum, with a comparison of 10 pregnant women who examined their contents there were about 4 pregnant women who complained of excessive nausea and vomiting. Objective: to determine the hyperemesis Gravidarum of pregnant mother in clinic. Methods: This study used Qualitative research methods by using a case study approach (Case Study.) Result: The description of excessive nausea of vomiting in women with Hipermemsis Gravidarum is continuous nausea and vomiting more than 10 times in one day, no appetite or vomiting when fed, the body feels weak, blood pressure decreases until the body weight decreases and interferes with daily activities days The factors that influence the occurrence of Hyperemesis Gravidarum are Hormonal, Diet, Unwanted Pregnancy, and psychology, primigravida does not affect the occurrence of Hyperemesis Gravidarum. Conclusion: Mothers who experience Hyperemesis Gravidarum feel nausea vomiting continuously more than 10 times in one day, no appetite or vomiting when fed, the body feels weak, blood pressure decreases until the weight decreases and interferes with daily activities, it is because there are several factors, namely, hormonal actors, diet, unwanted pregnancy, and psychology.


2018 ◽  
Vol 6 (9) ◽  
Author(s):  
DR.MATHEW GEORGE ◽  
DR.LINCY JOSEPH ◽  
MRS.DEEPTHI MATHEW ◽  
ALISHA MARIA SHAJI ◽  
BIJI JOSEPH ◽  
...  

Blood pressure is the force of blood pushing against blood vessel walls as the heart pumps out blood, and high blood pressure, also called hypertension, is an increase in the amount of force that blood places on blood vessels as it moves through the body. Factors that can increase this force include higher blood volume due to extra fluid in the blood and blood vessels that are narrow, stiff, or clogged(1). High blood pressure can damage blood vessels in the kidneys, reducing their ability to work properly. When the force of blood flow is high, blood vessels stretch so blood flows more easily. Eventually, this stretching scars and weakens blood vessels throughout the body, including those in the kidneys.


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