Systemic Evaluation of Vascular Dysfunction by High‐Resolution Sonography in an <i>N</i><sub>ω</sub>‐Nitro‐<scp>l</scp>‐Arginine Methyl Ester Hydrochloride–Induced Mouse Model of Preeclampsia‐Like Symptoms

Zhao, Ying; Yang, Ning; Li, Hanying; Cai, Wei; Zhang, Xin; Ma, Yuanfang; Niu, Xiulong; Gao, Yang; Zhou, Xin; Li, Yuming

doi:10.1002/jum.14380

Cited by 9 publications

(5 citation statements)

References 28 publications

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“…To verify the therapeutic effect of TGD on PE in vivo , we next took advantage of the L-NAME-induced PE mouse model as described previously ( Zhao et al, 2018 ). Schematization of the procedures and treatments was shown in Figure 4A .…”

Section: Resultsmentioning

confidence: 99%

Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against Preeclampsia via Regulation of Oxidative Stress and NO Signaling

et al. 2022

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Preeclampsia (PE), a pregnancy-specific syndrome with the major molecular determinants of placenta-borne oxidative stress and consequently impaired nitric oxide (NO) generation, has been considered to be one of the leading causes of maternal morbidity as well as mortality and preterm delivery worldwide. Several medical conditions have been found to be associated with increased PE risk, however, the treatment of PE remains unclear. Here, we report that Tianma Gouteng Decoction (TGD), which is used clinically for hypertension treatment, regulates oxidative stress and NO production in human extravillous trophoblast-derived TEV-1 cells. In human preeclamptic placental explants, reactive oxygen species (ROS) levels were elevated and NO production was inhibited, while TGD treatment at different periods effectively down-regulated the H2O2-induced ROS levels and significantly up-regulated the H2O2-suppressed NO production in human TEV-1 cells. Mechanistically, TGD enhanced the activity of total nitric oxide synthase (TNOS), which catalyze L-arginine oxidation into NO, and simultaneously, TGD promoted the expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), two isoforms of nitric oxide synthetases (NOS) in human placenta, resulting in the increased NO generation. More importantly, TGD administration not only increased the weight gain during pregnancy and revealed a hypotensive effect, but also improved the placental weight gain and attenuated fetal growth restriction in an NG-nitro-L-arginine methyl ester (L-NAME)-induced mouse PE-like model. Our results thereby provide new insights into the role of TGD as a potentially novel treatment for PE.

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Section: Resultsmentioning

confidence: 99%

Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against Preeclampsia via Regulation of Oxidative Stress and NO Signaling

et al. 2022

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“…It is possible that the kidney damage was not severe enough to cause proteinuria in this model. Others have reported L-NAME in mouse models demonstrate proteinuria, but these studies have based this finding on altered total urine protein ( 32 , 35 , 36 ), albumin alone ( 33 ), or creatinine alone ( 31 ), and not the albumin to creatinine ratio, which is a better measure, and used clinically. Furthermore, we did not find changes in expression of genes associated with kidney damage or dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…L-NAME was initially used to model preeclampsia in rats, inducing increased blood pressure, proteinuria, thrombocytopenia and fetal growth restriction ( 22 ). Since then, L-NAME has also been used to induce a preeclampsia-like phenotype in mice , inducing increased blood pressure, proteinuria, fetal growth restriction, impairment of placental morphology and other major organ and vascular alterations ( 30 , 31 , 32 , 33 , 34 , 35 , 36 ). However, these murine studies using L-NAME differ in their protocols, using varied concentrations of L-NAME, routes of administration, timing of exposure, and murine strains, that could respond differently to L-NAME ( 37 ).…”

Section: Introductionmentioning

confidence: 99%

The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health

et al. 2022

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Preeclampsia affects ∼2–8% of pregnancies worldwide. It is associated with increased long-term maternal cardiovascular disease risk. This study assesses the effect of the vasoconstrictor N(ω)-nitro-L-arginine methyl ester (L-NAME) in modelling preeclampsia in mice, and its long-term effects on maternal cardiovascular health. In this study, we found that L-NAME administration mimicked key characteristics of preeclampsia, including elevated blood pressure, impaired fetal and placental growth, and increased circulating endothelin-1 (vasoconstrictor), soluble fms-like tyrosine kinase-1 (anti-angiogenic factor), and C-reactive protein (inflammatory marker). Post-delivery, mice that received L-NAME in pregnancy recovered, with no discernible changes in measured cardiovascular indices at 1-, 2-, and 4-wk post-delivery, compared with matched controls. At 10-wk post-delivery, arteries collected from the L-NAME mice constricted significantly more to phenylephrine than controls. In addition, these mice had increased kidney Mmp9:Timp1 and heart Tnf mRNA expression, indicating increased inflammation. These findings suggest that though administration of L-NAME in mice certainly models key characteristics of preeclampsia during pregnancy, it does not appear to model the adverse increase in cardiovascular disease risk seen in individuals after preeclampsia.

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“…All mice were permitted free access to chow and tap water. BP was dynamically measured in conscious mice using the tail-cuff method as previous described [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

Pseudolaric Acid B Attenuates High Salt Intake-Induced Hypertensive Left Ventricular Remodeling by Modulating Monocyte/Macrophage Phenotypes

Yu¹,

Gao²,

Chen³

et al. 2021

Med Sci Monit

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Background Studies in ApoE knockout mice have shown that pseudolaric acid B (PB) can act as an immunomodulatory drug and attenuate atherosclerosis progression by modulating monocyte/macrophage phenotypes. Our previous study demonstrated that high salt intake could shift the phenotype of monocytes/macrophages to an inflammatory phenotype, and that this shift was related to hypertension and hypertensive left ventricular (LV) remodeling. However, no comprehensive assessment of the effects of PB on hypertensive LV remodeling has been conducted. Material/Methods In this study, RAW264.7 macrophages cultured with different concentrations of NaCl were used to investigate the modulating effects of PB on macrophage phenotype. Furthermore, N -nitro-l-arginine methyl ester hypertensive mice were used to investigate the modulating effects of PB on monocyte phenotype. LV remodeling was investigated by echocardiography. LV morphologic staining (for cardiomyocyte hypertrophy and collagen deposition) was performed at the time of sacrifice. Results The results showed that PB significantly improved the viability of RAW264.7 cells, suppressed their phagocytic and migration abilities, and inhibited their phenotypic shift to M1 macrophages. In addition, the blood pressure of PB-treated mice was significantly decreased relative to that of control mice. Furthermore, after PB treatment, the percentage of Ly6C hi monocytes was significantly decreased while that of Ly6C lo monocytes was apparently increased. Moreover, PB preserved LV function and alleviated myocardial fibrosis and cardiomyocyte hypertrophy as measured at the end of the experimental period. The transfer of monocytes from PB-treated mice to hypertensive mice achieved the same effects. Conclusions Together, these findings indicate that PB exerts its protective effects on hypertensive LV remodeling by modulating monocyte/macrophage phenotypes and warrants further investigation.

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Systemic Evaluation of Vascular Dysfunction by High‐Resolution Sonography in an N_ω‐Nitro‐l‐Arginine Methyl Ester Hydrochloride–Induced Mouse Model of Preeclampsia‐Like Symptoms

Cited by 9 publications

References 28 publications

Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against Preeclampsia via Regulation of Oxidative Stress and NO Signaling

Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against Preeclampsia via Regulation of Oxidative Stress and NO Signaling

The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health

Pseudolaric Acid B Attenuates High Salt Intake-Induced Hypertensive Left Ventricular Remodeling by Modulating Monocyte/Macrophage Phenotypes

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Systemic Evaluation of Vascular Dysfunction by High‐Resolution Sonography in an Nω‐Nitro‐l‐Arginine Methyl Ester Hydrochloride–Induced Mouse Model of Preeclampsia‐Like Symptoms

Cited by 9 publications

References 28 publications

Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against Preeclampsia via Regulation of Oxidative Stress and NO Signaling

Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against Preeclampsia via Regulation of Oxidative Stress and NO Signaling

The L-NAME mouse model of preeclampsia and impact to long-term maternal cardiovascular health

Pseudolaric Acid B Attenuates High Salt Intake-Induced Hypertensive Left Ventricular Remodeling by Modulating Monocyte/Macrophage Phenotypes

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Systemic Evaluation of Vascular Dysfunction by High‐Resolution Sonography in an N_ω‐Nitro‐l‐Arginine Methyl Ester Hydrochloride–Induced Mouse Model of Preeclampsia‐Like Symptoms