scholarly journals Sulfur dioxide improves endothelial dysfunction by downregulating the angiotensin II/AT1R pathway in D-galactose-induced aging rats

2018 ◽  
Vol 19 (2) ◽  
pp. 147032031877889 ◽  
Author(s):  
Jing Dai ◽  
Rui Liu ◽  
Jinjie Zhao ◽  
Aijie Zhang
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Sulfur Dioxide ◽  
Vascular Tissue ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Control Group ◽  
Stress Injury ◽  
Aging Rats

The aim of this study was to investigate the protective effects of sulfur dioxide (SO2) on the endothelial function of the aorta in D-galactose (D-gal)-induced aging rats. Sprague Dawley rats were randomized into a D-gal group, a D-gal + SO2 group and a control group, then injected with D-gal, D-gal + SO2 donor or equivalent volumes of saline, respectively, for 8 consecutive weeks. After 8 weeks, the mean arterial pressure was significantly increased in the D-gal group, but was lowered by SO2. SO2 significantly ameliorated the endothelial dysfunction induced by D-gal treatment. The vasorelaxant effect of SO2 was associated with the elevated nitric oxide levels and upregulated phosphorylation of endothelial nitric oxide synthase. In the D-gal group, the concentration of angiotensin II in the plasma was significantly increased, but was decreased by SO2. Moreover, levels of vascular tissue hydrogen peroxide (H2O2) and malondialdehyde were significantly lower in SO2-treated groups than those in the D-gal group. Western blot analysis showed that the expressions of oxidative stress-related proteins (the angiotensin II type 1 receptor (AT1R), and nicotinamide adenine dinucleotide phosphate oxidase subunits) were increased in the D-gal group, while they were decreased after treatment with SO2. In conclusion, SO2 attenuated endothelial dysfunction in association with the inhibition of oxidative stress injury and the downregulation of the angiotensin II/AT1R pathway in D-gal-induced aging rats.

scholarly journals Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia

2008 ◽  
Vol 295 (4) ◽  
pp. F1134-F1141 ◽  
Author(s):  
Laura G. Sánchez-Lozada ◽  
Virgilia Soto ◽  
Edilia Tapia ◽  
Carmen Avila-Casado ◽  
Yuri Y. Sautin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Uric Acid ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Systemic Hypertension ◽  
Sprague Dawley ◽  
Renal Vasoconstriction ◽  
Renal Abnormalities ◽  
Oxonic Acid

Endothelial dysfunction is a characteristic feature during the renal damage induced by mild hyperuricemia. The mechanism by which uric acid reduces the bioavailability of intrarenal nitric oxide is not known. We tested the hypothesis that oxidative stress might contribute to the endothelial dysfunction and glomerular hemodynamic changes that occur with hyperuricemia. Hyperuricemia was induced in Sprague-Dawley rats by administration of the uricase inhibitor, oxonic acid (750 mg/kg per day). The superoxide scavenger, tempol (15 mg/kg per day), or placebo was administered simultaneously with the oxonic acid. All groups were evaluated throughout a 5-wk period. Kidneys were fixed by perfusion and afferent arteriole morphology, and tubulointerstitial 3-nitrotyrosine, 4-hydroxynonenal, NOX-4 subunit of renal NADPH-oxidase, and angiotensin II were quantified. Hyperuricemia induced intrarenal oxidative stress, increased expression of NOX-4 and angiotensin II, and decreased nitric oxide bioavailability, systemic hypertension, renal vasoconstriction, and afferent arteriolopathy. Tempol treatment reversed the systemic and renal alterations induced by hyperuricemia despite equivalent hyperuricemia. Moreover, because tempol prevented the development of preglomerular damage and decreased blood pressure, glomerular pressure was maintained at normal values as well. Mild hyperuricemia induced by uricase inhibition causes intrarenal oxidative stress, which contributes to the development of the systemic hypertension and the renal abnormalities induced by increased uric acid. Scavenging of the superoxide anion in this setting attenuates the adverse effects induced by hyperuricemia.

scholarly journals Role of oxidative stress in multiparity-induced endothelial dysfunction

2008 ◽  
Vol 295 (4) ◽  
pp. H1736-H1742 ◽  
Author(s):  
Huda E. Tawfik ◽  
Jonathan Cena ◽  
Richard Schulz ◽  
Susan Kaufman
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Coronary Arteries ◽  
Vascular Tissue ◽  
Fold Increase ◽  
Oxidase Inhibitor ◽  
Maximal Response ◽  
Protein Levels ◽  
Increased Risk

Multiparity is associated with increased risk of cardiovascular disease. We tested whether multiparity induces oxidative stress in rat vascular tissue. Coronary arteries and thoracic aorta were isolated from multiparous and age-matched virgin rats. Relaxation to ACh and sodium nitroprusside (SNP) was measured by wire myography. We also tested the effect of the superoxide dismutase mimetic MnTE2PyP (30 μM), the NADPH oxidase inhibitor apocynin (10 μM), and the peroxynitrite scavenger FeTPPs (10 μM) on ACh-mediated relaxation in coronary arteries. Vascular superoxide anion was measured using the luminol derivative L-012 and nitric oxide (NO) generation by the Griess reaction. Multiparity reduced maximal response and sensitivity to ACh in coronary arteries [maximal relaxation (Emax): multiparous 49 ± 3% vs. virgins 95% ± 3%; EC50: multiparous 135 ± 1 nM vs. virgins 60 ± 1 nM], and in aortic rings (Emax: multiparous 38 ± 3% vs. virgins 79 ± 4%; EC50: multiparous 160 ± 2 nM vs. virgins 90 ± 3 nM). Coronary arteries from the two groups relaxed similarly to SNP. Superoxide anions formation was significantly higher in both coronary arteries (2.8-fold increase) and aorta (4.1-fold increase) from multiparous rats compared with virgins. In multiparous rats, incubation with MnTE2PyP, apocynin, and FeTPPs improved maximal relaxation to ACh (MnTE2PyP: 74 ± 5%; vehicle: 41 ± 5%; apocynin: 73 ± 3% vs. vehicle: 41 ± 3%; FeTPPs: 72 ± 3% vs. vehicle: 46 ± 3%) and increased sensitivity (EC50: MnTE2PyP: 61 ± 0.5 nM vs. vehicle: 91 ± 1 nM; apocynin: 45 ± 3 nM vs. vehicle: 91 ± 6 nM; FeTPP: 131 ± 2 nM vs. vehicle: 185 ± 1 nM). Multiparity also reduced total nitrate/nitrite levels (multiparous: 2.5 ± 2 μmol/mg protein vs. virgins: 7 ± 1 μmol/mg protein) and endothelial nitric oxide synthase protein levels (multiparous: 0.53 ± 0.1 protein/actin vs. virgins: 1.0 ± 0.14 protein/actin). These data suggest that multiparity induces endothelial dysfunction through decreased NO bioavailability and increased reactive oxygen species formation.

scholarly journals Naringin Reverses High-Cholesterol Diet-Induced Vascular Dysfunction and Oxidative Stress in Rats via Regulating LOX-1 and NADPH Oxidase Subunit Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Sirinat Pengnet ◽  
Sakdina Prommaouan ◽  
Phinsuda Sumarithum ◽  
Wachirawadee Malakul
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Oxidative Damage ◽  
Nadph Oxidase ◽  
Vascular Function ◽  
Antioxidant Properties ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
High Cholesterol Diet ◽  
Sprague Dawley

Hypercholesterolaemia is associated with oxidative stress and endothelial dysfunction and leads to the development of atherosclerosis. Naringin exhibits cardiovascular protective and antioxidant properties. Therefore, the aim of this study was to assess the effect of naringin administration on vascular oxidative stress and endothelial dysfunction in hypercholesterolaemic rats and to elucidate its underlying mechanism. Sprague Dawley rats were fed a diet with 1.5% cholesterol (HCD) for 8 weeks to induce hypercholesterolaemia. Naringin (100 mg/kg body weight) was orally administrated to rats during the last 4 weeks of the diet treatment. After 8 weeks, the thoracic aorta was isolated to determine vascular function and nitric oxide (NO) levels. The aortic superoxide anion (O2−) level was detected using dihydroethidium (DHE) fluorescence staining. Protein expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, and inducible nitric oxide synthase (iNOS), as well as oxidative damage markers, was also evaluated in aortae. Naringin treatment of hypercholesterolaemic rats enhanced aortic NO levels, restored endothelium-dependent responses to acetylcholine (ACh), and reduced aortic O2− levels. Furthermore, naringin treatment decreased LOX-1, NADPH oxidase subunits (p47phox, Nox2, and Nox4), and iNOS as well as oxidative damage markers (3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE)) expression in aortic tissues from hypercholesterolaemic rats. These results demonstrate that naringin treatment improves endothelium dysfunction in hypercholesterolaemic rats, at least partially by decreasing oxidative stress via downregulation of LOX-1 and NADPH oxidase.

scholarly journals Effect of oxidative stress on endothelium in patients with heart failure and type 2 diabetes ­mellitus

2020 ◽  
Vol 101 (1) ◽  
pp. 13-17
Author(s):  
F I Mammadova
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Heart Failure ◽  
Endothelial Dysfunction ◽  
Control Group

Aim. To estimate the severity of endothelial dysfunction and effects of nitric oxide, thiol status and cystatin on the progression of chronic heart failure and chronic heart failure in type 2 diabetes mellitus. Methods. 80 patients (men and women) with chronic heart failure were included. All patients were divided into two groups: the first group 39 patients with chronic heart failure, the second 41 people with chronic heart failure and type 2 diabetes mellitus. The control group consists of 20 healthy donors. To obtain statistically significant differences with the control group the minimum sample size for observations was determined based on the target variance of a small sample (n=10). The lipid profile and carbohydrate metabolism, endothelin-1, cystatin, nitric oxide were evaluated. Statistical processing was performed using Microsoft Office Excel and IBM SPSS Statistics 20 software. Results. Changes in lipid metabolism were found in both groups, while an increase in carbohydrate metabolism was observed in patients with chronic heart failure with type 2 diabetes mellitus. Under conditions of oxidative stress in patients with chronic heart failure, a decrease in the content of thiol status and an increase in the amount of nitric oxide in the blood serum were recorded. The endothelin-1 level was elevated, particularly in the second group, which indicates a more serious endothelial dysfunction with increased glucose content in patients with chronic heart failure. Conclusion. The level of cystatin C as an atherogenic risk factor was equally increased in the studied patients, possibly it affected by the rate of disease progression; feasible to use these markers to detect the progression of chronic heart failure in the early stages.

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

scholarly journals Endothelial dysfunction and body mass index: is there a role for plasma peroxynitrite?

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Theresa Chikopela ◽  
Douglas C. Heimburger ◽  
Longa Kaluba ◽  
Pharaoh Hamambulu ◽  
Newton Simfukwe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Body Mass ◽  
Vascular Function ◽  
Aortic Ring ◽  
Normal Weight ◽  
Oxide Synthase ◽  
Weight Groups

Abstract Background Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The endothelium ability to produce nitric oxide is one of the most crucial mechanisms in regulating vascular tone. An increase in inducible nitric oxide synthase contributes to endothelial dysfunction in overweight persons, while oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo) in underweight persons. The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight, normal weight and overweight), with four treatment arms in each. Plasma nitrotyrosine levels were measured 15–20 h post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial-dependent and endothelial-independent vascular relaxation after pre-constriction of aortic rings with phenylephrine. Results Nitrotyrosine levels in saline-treated rats were similar among the weight groups. There was a significant increase in nitrotyrosine levels between saline-treated rats and those treated with the highest lipopolysaccharide doses in each of the weight groups. In response to ACh challenge, Rmax (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower Rmax in the underweight rats (106%) compared to the normal weight rats (112%). Overweight rats had a significant decrease in Rmax (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower Rmax accompanied an increase in peroxynitrite after acetylcholine challenge in all weight groups. Conclusions Endothelial dysfunction, observed as an impairment in the ability to reduce tension, is associated with increased plasma peroxynitrite levels across the spectrum of body mass. In higher-BMI rats, an additional role is played by vascular smooth muscle in the causation of endothelial dysfunction.

scholarly journals Endothelial PPAR-γ provides vascular protection from IL-1β-induced oxidative stress

2016 ◽  
Vol 310 (1) ◽  
pp. H39-H48 ◽  
Author(s):  
Masashi Mukohda ◽  
Madeliene Stump ◽  
Pimonrat Ketsawatsomkron ◽  
Chunyan Hu ◽  
Frederick W. Quelle ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Nitric Oxide Synthase ◽  
Transgenic Mice ◽  
Stress Responses ◽  
Endothelial Nitric Oxide Synthase ◽  
Ppar Γ ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Loss of peroxisome proliferator-activated receptor (PPAR)-γ function in the vascular endothelium enhances atherosclerosis and NF-κB target gene expression in high-fat diet-fed apolipoprotein E-deficient mice. The mechanisms by which endothelial PPAR-γ regulates inflammatory responses and protects against atherosclerosis remain unclear. To assess functional interactions between PPAR-γ and inflammation, we used a model of IL-1β-induced aortic dysfunction in transgenic mice with endothelium-specific overexpression of either wild-type (E-WT) or dominant negative PPAR-γ (E-V290M). IL-1β dose dependently decreased IκB-α, increased phospho-p65, and increased luciferase activity in the aorta of NF-κB-LUC transgenic mice. IL-1β also dose dependently reduced endothelial-dependent relaxation by ACh. The loss of ACh responsiveness was partially improved by pretreatment of the vessels with the PPAR-γ agonist rosiglitazone or in E-WT. Conversely, IL-1β-induced endothelial dysfunction was worsened in the aorta from E-V290M mice. Although IL-1β increased the expression of NF-κB target genes, NF-κB p65 inhibitor did not alleviate endothelial dysfunction induced by IL-1β. Tempol, a SOD mimetic, partially restored ACh responsiveness in the IL-1β-treated aorta. Notably, tempol only modestly improved protection in the E-WT aorta but had an increased protective effect in the E-V290M aorta compared with the aorta from nontransgenic mice, suggesting that PPAR-γ-mediated protection involves antioxidant effects. IL-1β increased ROS and decreased the phospho-endothelial nitric oxide synthase (Ser1177)-to-endothelial nitric oxide synthase ratio in the nontransgenic aorta. These effects were completely abolished in the aorta with endothelial overexpression of WT PPAR-γ but were worsened in the aorta with E-V290M even in the absence of IL-1β. We conclude that PPAR-γ protects against IL-1β-mediated endothelial dysfunction through a reduction of oxidative stress responses but not by blunting IL-1β-mediated NF-κB activity.

Renal endothelial dysfunction and impaired autoregulation after ischemia-reperfusion injury result from excess nitric oxide

2006 ◽  
Vol 291 (3) ◽  
pp. F619-F628 ◽  
Author(s):  
Zhengrong Guan ◽  
Glenda Gobé ◽  
Desley Willgoss ◽  
Zoltán H. Endre
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Tubuloglomerular Feedback ◽  
Sprague Dawley ◽  
Endothelial Nitric Oxide

Endothelial dysfunction in ischemic acute renal failure (IARF) has been attributed to both direct endothelial injury and to altered endothelial nitric oxide synthase (eNOS) activity, with either maximal upregulation of eNOS or inhibition of eNOS by excess nitric oxide (NO) derived from iNOS. We investigated renal endothelial dysfunction in kidneys from Sprague-Dawley rats by assessing autoregulation and endothelium-dependent vasorelaxation 24 h after unilateral (U) or bilateral (B) renal artery occlusion for 30 (U30, B30) or 60 min (U60, B60) and in sham-operated controls. Although renal failure was induced in all degrees of ischemia, neither endothelial dysfunction nor altered facilitation of autoregulation by 75 pM angiotensin II was detected in U30, U60, or B30 kidneys. Baseline and angiotensin II-facilitated autoregulation were impaired, methacholine EC50 was increased, and endothelium-derived hyperpolarizing factor (EDHF) activity was preserved in B60 kidneys. Increasing angiotensin II concentration restored autoregulation and increased renal vascular resistance (RVR) in B60 kidneys; this facilitated autoregulation, and the increase in RVR was abolished by 100 μM furosemide. Autoregulation was enhanced by Nω-nitro-l-arginine methyl ester. Peri-ischemic inhibition of inducible NOS ameliorated renal failure but did not prevent endothelial dysfunction or impaired autoregulation. There was no significant structural injury to the afferent arterioles with ischemia. These results suggest that tubuloglomerular feedback is preserved in IARF but that excess NO and probably EDHF produce endothelial dysfunction and antagonize autoregulation. The threshold for injury-producing, detectable endothelial dysfunction was higher than for the loss of glomerular filtration rate. Arteriolar endothelial dysfunction after prolonged IARF is predominantly functional rather than structural.

Mercury Exposure and Endothelial Dysfunction

2015 ◽  
Vol 34 (4) ◽  
pp. 300-307 ◽  
Author(s):  
Swati Omanwar ◽  
M. Fahim
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Vascular Endothelium ◽  
Circulatory System ◽  
Vital Role ◽  
Mercury Exposure ◽  
And Function ◽  
The Impact ◽  
And Oxidative Stress

Vascular endothelium plays a vital role in the organization and function of the blood vessel and maintains homeostasis of the circulatory system and normal arterial function. Functional disruption of the endothelium is recognized as the beginning event that triggers the development of consequent cardiovascular disease (CVD) including atherosclerosis and coronary heart disease. There is a growing data associating mercury exposure with endothelial dysfunction and higher risk of CVD. This review explores and evaluates the impact of mercury exposure on CVD and endothelial function, highlighting the interplay of nitric oxide and oxidative stress.

scholarly journals Inflammatory Monocytes Determine Endothelial Nitric-oxide Synthase Uncoupling and Nitro-oxidative Stress Induced by Angiotensin II

2014 ◽  
Vol 289 (40) ◽  
pp. 27540-27550 ◽  
Author(s):  
Sabine Kossmann ◽  
Hanhan Hu ◽  
Sebastian Steven ◽  
Tanja Schönfelder ◽  
Daniela Fraccarollo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Inflammatory Monocytes ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide
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