Melatonin attenuates hypertension and oxidative stress in a rat model of L-NAME-induced gestational hypertension

Preeclampsia is a life-threatening multiorgan systemic disease with manifestations including gestational hypertension, oxidative stress, and vascular dysfunction. We aimed to evaluate the therapeutic effects of melatonin on an L-NAME (NLG-nitro-l-arginine methyl ester)-induced rat preeclampsia model. During gestation, L-NAME was added to drinking water at 50 mg/kg/day from gestation day (GD) 8. Rats received the combination of L-NAME with melatonin (10 mg/kg/day), or aspirin (1.5 mg/kg/day), and rats that received only L-NAME or no treatments were used as controls. Aspirin was mixed with rodent chow and melatonin was administered intraperitoneally. Blood pressure and urine protein content were monitored every 3 days. On GD19, blood samples were collected for biochemical analysis. Compared to untreated L-NAME rats, melatonin led to markedly lowered blood pressure and urine protein content, and recovery in the fetus alive ratio, fetal weight, and the fetal weight/placental weight ratio. Compared to untreated L-NAME rats, plasma antioxidant capacity and plasma malondialdehyde were increased and decreased by melatonin, respectively, in L-NAME rats. Melatonin treatment also reduced sFlt-1, increased PlGF, and decreased the sFlt-1/PlGF ratio. In the placenta, melatonin also reduced sFlt-1 levels and increased Nrf2, PlGF, and HO-1 levels. We have demonstrated in a rat model of preeclampsia that melatonin exerts significant protective effects through lowering blood pressure and reducing oxidative stress.

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Magnesium Lithospermate B Downregulates the Levels of Blood Pressure, Inflammation, and Oxidative Stress in Pregnant Rats with Hypertension

International Journal of Hypertension ◽

10.1155/2020/6250425 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Kaixiang Xu ◽

Xiaohong Zang ◽

Mian Peng ◽

Qian Zhao ◽

Binbin Lin

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Gestational Hypertension ◽

Protective Effects ◽

Urine Protein ◽

Pregnant Rats ◽

Protein Levels ◽

Arterial Blood ◽

Magnesium Lithospermate B ◽

And Oxidative Stress

Background. Magnesium lithospermate B (MLB) was shown to suppress oxidative stress and reduce hypertension, but the role of MLB in pregnancy-induced hypertension (PIH) remains unknown. The objective of this study was to demonstrate the effects of MLB on rats with PIH. Methods. A total of 40 pregnant SD rats were selected, and 30 rats were orally given NG-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg/day) to establish PIH rat models. Rats were equally divided into four groups: control, PIH, 5 mg/kg MLB, and 10 mg/kg MLB. MLB was consecutively administered into PIH rats for one week. The effects of MLB on mean arterial blood pressure (MAP), urine protein level, inflammation, and oxidative stress together with angiogenesis were analyzed. Results. MLB prevented the elevation in MAP and urine protein levels induced by L-NAME. The activities of inflammatory cytokines were highly increased in serum and placental tissues of PIH rats, while cotreatment with MLB partially reversed the activities of these cytokines. MLB also recovered the expression of reactive oxygen species (ROS) in plasma of PIH rats together with levels of oxidative stress and antioxidant capacity in the placenta of PIH rats. The decreased expressions of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and NO observed in PIH rats were increased by MLB. In addition, 10 mg/kg MLB exhibited higher protective effects as compared to lower doses of 5 mg/kg. Conclusion. This study demonstrated that pretreatment with MLB decreased MAP, inflammation, and oxidative stress in rats with gestational hypertension.

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A Subpressor Dose of Angiotensin II Elevates Blood Pressure in a Normotensive Rat Model by Oxidative Stress

Physiological Research ◽

10.33549/physiolres.932738 ◽

2015 ◽

pp. 153-159 ◽

Cited By ~ 1

Author(s):

M. M. GOVENDER ◽

A. NADAR

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Angiotensin Ii ◽

Mrna Expression ◽

Rat Model ◽

Wistar Rat ◽

Control Group ◽

Sod Activity ◽

Male Wistar Rats ◽

Experimental Group

Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2− production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat.

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Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders

BioMed Research International ◽

10.1155/2014/946492 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Akinobu Maeda ◽

Kouichi Tamura ◽

Hiromichi Wakui ◽

Masato Ohsawa ◽

Kengo Azushima ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Adipose Tissue ◽

Metabolic Disorders ◽

Visceral Obesity ◽

Pleiotropic Effects ◽

Stress Axis ◽

Therapeutic Effects ◽

Kkay Mice ◽

Adipocyte Hypertrophy

In the present study, we examined the therapeutic effects of olmesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders with visceral obesity, with a focus on an olmesartan effect on the adipose tissue. Olmesartan treatment (3 mg/kg per day) for 4 weeks significantly lowered systolic blood pressure but did not affect body weight during the study period in KKAy mice. However, there were three interesting findings possibly related to the pleiotropic effects of olmesartan on adipose tissue in KKAy mice: (1) an inhibitory effect on adipocyte hypertrophy, (2) a suppressive effect on IL-6 gene expression, and (3) an ameliorating effect on oxidative stress. On the other hand, olmesartan exerted no evident influence on the adipose tissue expression of AT1R-associated protein (ATRAP), which is a molecule interacting with AT1R so as to inhibit pathological AT1R activation and is suggested to be an emerging molecular target in metabolic disorders with visceral obesity. Collectively, these results suggest that the blood pressure lowering effect of olmesartan in KKAy mice is associated with an improvement in adipocyte, including suppression of adipocyte hypertrophy and inhibition of the adipose IL-6-oxidative stress axis. Further study is needed to clarify the functional role of adipose ATRAP in the pleiotropic effects of olmesartan.

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Cadmium acts as a silent killer of liver by inducing oxidative stress and hepatocellular injury and a possible amelioration by vitamin B12 and folic acid in rat model

Progress in Health Sciences ◽

10.5604/01.3001.0013.3696 ◽

2019 ◽

Vol 1 ◽

pp. 105-117

Author(s):

A. Banerjee ◽

P. Nandi ◽

C. Bhattacharya ◽

Z. Kabir ◽

S. Mukherjee ◽

...

Keyword(s):

Oxidative Stress ◽

Folic Acid ◽

Vitamin B12 ◽

Rat Model ◽

Male Rats ◽

Albino Rats ◽

Therapeutic Effects ◽

Hepatocellular Injury ◽

Male Adult ◽

Wistar Albino Rats

Purpose: To investigate the involvement of oxidative stress in Cadmium (Cd) induced alteration in the functional status of the liver. And to assess the efficacy of folic acid and vitamin B12 in preventing Cd-induced damage in the same. Materials and methods: The experiment was carried out for four weeks. For the experiment, 25 healthy male adult Wistar albino rats were randomly selected and were divided into five equal groups and treated as control, treated with Cd, supplemented with vitamin B12 and folic acid and in the combination of these two. After 28 days the liver function enzymes and oxidative stress parameters were measured. Results: Cd is the silent killer of the hepatic system through the induction of oxidative stress in male rats. From this investigation, it is evident that the folic acid+vitamin B12 possess significant hepatoprotective and antioxidant activity against Cd-induced hepatotoxicity in the rat model. In addition, results revealed that the folic acid alone and or in combination with vitamin B12 blunted the hepatotoxic effect significantly. Conclusions: Based on results obtained, it can be concluded that folic acid and vitamin B12 offer a protective effect in Cd-induced oxidative stress associated with hepatocellular injury. Folic acid and vitamin B12 can be considered as a potent natural antioxidant which has the capacity to provide protection against Cd-induced oxidative stress in the liver in rats. However, to elucidate the exact mechanism of this modulatory effect and to examine its potential therapeutic effects further studies are essential.

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Comparative effects of N-acetyl-l-cysteine and ramipril on arterial hypertension, insulin resistance, and oxidative stress in chronically glucose-fed rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y08-090 ◽

2008 ◽

Vol 86 (11) ◽

pp. 752-760 ◽

Cited By ~ 25

Author(s):

Adil El Midaoui ◽

Mahmoud Ali Ismael ◽

Huogen Lu ◽

I. George Fantus ◽

Jacques de Champlain ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Blood Pressure ◽

Nadph Oxidase ◽

Plasma Levels ◽

Superoxide Anion ◽

Oxidase Activity ◽

Therapeutic Effects ◽

Superoxide Anion Production ◽

Nadph Oxidase Activity

Beneficial effects of an antioxidant (N-acetyl-l-cysteine, NAC) and an angiotensin I-converting enzyme (ACE) inhibitor (ramipril) were assessed in a rat model of insulin resistance induced by 10% glucose feeding for 20 weeks. Treatments with NAC (2 g/kg per day) and ramipril (1 mg/kg per day) were initiated at 16 weeks in the drinking fluid. Systolic blood pressure, plasma levels of insulin and glucose, and insulin resistance were significantly higher in rats treated with glucose for 20 weeks. This was associated with a higher production of superoxide anion and NADPH oxidase activity in aorta and liver and with a marked reduction in protein expression of skeletal muscle insulin receptor substrate-1 (IRS-1) in the gastrocnemius muscle. NAC prevented all these alterations. Although ramipril also reversed high blood pressure, it had a lesser effect on insulin resistance (including IRS-1) and blocked superoxide anion production only in aorta. Ramipril, in contrast to NAC, did not reduce NADPH oxidase activity in aorta and liver or plasma levels of 4-hydroxynonenal and malondialdehyde. Results suggest that the inhibition of the oxidative stress in hypertensive and insulin-resistant states contributes to the therapeutic effects of NAC and ramipril. Whereas NAC exerts effective antioxidant activity in multiple tissues, ramipril appears to preferentially target the vasculature.

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P2534Prevalence and risk factors of acquired LQTS among pregnancy: a single-center study

European Heart Journal ◽

10.1093/eurheartj/ehz748.0863 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

D Han ◽

C F Sun ◽

G L Li

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Uric Acid ◽

Regression Analysis ◽

Twin Pregnancy ◽

Gestational Hypertension ◽

Fetal Weight ◽

Multivariable Logistic Regression Analysis ◽

Qtc Prolongation ◽

Significant Difference

Abstract Background Prolonged QT intervals have been observed in pregnant women, especially those with twin pregnancy, which predisposes them to a high risk of ventricular arrhythmias. Purpose To evaluate the prevalence of acquired long QT syndrome (aLQTS) in hospitalized parturient women with single and twin pregnancy and search for potential risk factors. Methods Information about age-matched parturient women with single and twin pregnancy were retrospectively collected in our hospital from January 2016 to June 2018. The prevalence of aLQTS was evaluated. The common risk factors for corrected QT (QTc) prolongation were compiled, and multivariable logistic regression analysis was used to evaluate how each factor was related to aLQTS in such population. Results Totally 293 parturient women (147 twin pregnancy, 50.17%) were included. The prevalence of aLQTS was 72.70% in all cases, 53.15% in the single pregnancy, 93.20% in the twin pregnancy. The proportion of severely prolonged QTc was 36.18% in all cases, 8.22% in the single pregnancy and 63.95% in the twin pregnancy. The QTc interval was much longer in the twin pregnancy than in the single pregnancy with significant difference. Differences in systolic blood pressure, diastolic blood pressure, total cholesterol, serum uric acid, fetal weight, QRS, RV5+SV1, Tp-Te, Tp-Te/QT have been revealed to be statistically significant between the QTc-prolongation group and the QTc-normal group. The incidence of gestational hypertension and twin pregnancy in the QTc-prolongation group were more prevalent than in the QTc-normal group with significant difference. In the multivariable logistic regression analysis, gestational hypertension, twin pregnancy, increase of diastolic blood pressure, high total cholesterol, high serum uric acid, and heavy fetal weight were identified to be associated with QTc prolongation in parturient women. Table 1. Risk factors significantly correlated with QTc prolongation in parturient women Index P value OR (95% CI) DBP (mmHg) 0.033* 1.052 (1.004 to 1.101) TC (mmol/L) 0.001** 1.442 (1.165 to 1.785) UA (μmol/L) 0.007** 1.004 (1.001 to 1.008) Fetal weight (g) <0.001** 1.001 (1.001 to 1.001) Hypertention (%) 0.029* 2.561 (1.099 to 5.967) Twin (%) <0.001** 12.618 (6.145 to 25.909) Conclusion To our knowledge, this is the first clinical study to evaluate the prevalence of aLQTS between single and twin pregnancy. The prevalence of aLQTS is much higher in the parturient women, particularly in twin pregnancy.

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Homeopathic Medicine Rauwolfia Serpentina Ameliorate Blood Pressure and Oxidative Stress Parameters of Kidney by Modulating Expression of Antioxidant Enzymes in Deoxycorticosterone Acetate (DOCA)-Salt-Induced Hypertensive Rat Model

Journal of Drug Research and Development ◽

10.16966/2470-1009.111 ◽

2016 ◽

Vol 2 (1) ◽

Cited By ~ 1

Author(s):

Kumar S

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Antioxidant Enzymes ◽

Rat Model ◽

Deoxycorticosterone Acetate ◽

Oxidative Stress Parameters ◽

Rauwolfia Serpentina ◽

Homeopathic Medicine ◽

And Oxidative Stress ◽

Stress Parameters

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Protective Effects of Pterostilbene Against Cardiac Oxidative Stressand Dysfunctionin Nicotine-Induced Cardiac Injury Rat Model

Biomedical & Pharmacology Journal ◽

10.13005/bpj/2164 ◽

2021 ◽

Vol 14 (02) ◽

pp. 623-633

Author(s):

Ahmad Rohi Ghazali ◽

Elancheleyen Mahindran ◽

Anand Ramalingam ◽

Liya Chee ◽

Satirah Zainalabidin

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Rat Model ◽

Systolic Dysfunction ◽

Cardiac Injury ◽

Left Ventricular ◽

Study Endpoint ◽

Tbars Level ◽

Protective Effects ◽

Sprague Dawley

Prolonged nicotine exposureescalates the onset and development of cardiovascular diseasesin both active and passive smokers via cardiac injury. Pterostilbene, a resveratrol derivative, has been shown to exhibit high anti-inflammatory,antioxidant and antitumor properties. Nevertheless, its role as a cardioprotective agent in a nicotine-induced rat model is still scarce. Therefore, our study was aimed to investigatethe effects of co-administered pterostilbene against nicotine-induced cardiac injury rat model.Twenty-six male Sprague-Dawley rats were randomly allotted and treated with nicotine (0.6 mg/kg)orin-combination with pterostilbene (10 mg/kg) for 28 consecutive days. Non-invasive tail cuff blood pressure measurements were taken atday-0, day-14 and day-28. Rat hearts were harvested at study endpoint and thechanges in cardiac function parameters and oxidative stress markers were evaluated. The findings have shown that pterostilbene co-administration significantly (P<0.05) reduced the blood pressure and ameliorated nicotine-induced cardiac systolic dysfunction by improving the left ventricular developed pressure (LVDP). In addition, pterostilbene also significantly (P <0.05)attenuatedthe thiobarbituric acid reactive substances (TBARS) level, indicative of protection against nicotine-induced cardiac oxidative stress. In summary, our findings suggest that pterostilbene has the potential to be developed as a natural alternative in protecting the cardiac injuryinduced by nicotine. However further studies are warranted to investigate its efficacy and the underlying mechanism in cardioprotection.

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Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00222.2014 ◽

2015 ◽

Vol 308 (3) ◽

pp. R163-R172 ◽

Cited By ~ 10

Author(s):

Jude S. Morton ◽

Anita Quon ◽

Po-Yin Cheung ◽

Tatsuya Sawamura ◽

Sandra T. Davidge

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Rat Model ◽

Salvia Miltiorrhiza ◽

Oxidized Ldl ◽

Maternal Blood ◽

Tanshinone Iia ◽

Sodium Tanshinone Iia Sulfonate ◽

Paf Receptor ◽

Maternal Blood Pressure

Preeclampsia is a disorder of pregnancy with a significant impact on maternal and fetal health. The complexity of this multifactorial condition has precluded development of effective therapies and, although many potential pathways have been investigated, the etiology still requires clarification. Our group has investigated the scavenger lectin-like oxidized LDL (LOX-1) receptor, which may respond to factors released from the distressed placenta that contribute to the vascular pathologies observed in preeclampsia. Given the known beneficial effects of sodium tanshinone IIA sulfonate (STS; a component of Salvia miltiorrhiza) on vasodilation, reduction of oxidative stress, and lipid profiles, we have investigated its role as a potential treatment strategy. We hypothesized that STS would improve vascular endothelial function and, combined with a reduction in oxidative stress, would improve pregnancy outcomes in a rat model of preeclampsia (reduced uteroplacental perfusion pressure, RUPP). We further hypothesized this may occur via the action of STS on the LOX-1 and/or platelet-activating factor (PAF) receptor axes. The RUPP model increased maternal blood pressure, vascular oxidative stress, and involvement of the vascular PAF receptor. Treatment with STS during pregnancy decreased both oxidative stress and involvement of the PAF receptor; however, it also increased involvement of the LOX-1 receptor, which is in line with the concept that scavenger receptors, such as LOX-1 and PAF, are upregulated in response to ligand binding and/or under pathological conditions. In this model of preeclampsia, however, the vascular actions of STS did not lead to improvements in pregnancy outcome such as fetal biometrics or maternal blood pressure.

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