Sex differences in nitrosative stress during renal ischemia

2010 ◽  
Vol 299 (5) ◽  
pp. R1387-R1395 ◽  
Author(s):  
Francisca Rodríguez ◽  
Susana Nieto-Cerón ◽  
Francisco J. Fenoy ◽  
Bernardo López ◽  
Isabel Hernández ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sex Differences ◽  
Nitric Oxide Synthase ◽  
Nitrosative Stress ◽  
Differential Pulse ◽  
Sprague Dawley ◽  
Oxidative And Nitrosative Stress ◽  
Sprague Dawley Rats ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Females. suffer a less severe ischemic acute renal failure than males, apparently because of higher nitric oxide (NO) bioavailability and/or lower levels of oxidative stress. Because the renal ischemic injury is associated with outer medullary (OM) endothelial dysfunction, the present study evaluated sex differences in OM changes of NO and peroxynitrite levels (by differential pulse voltammetry and amperometry, respectively) during 45 min of ischemia and 60 min of reperfusion in anesthetized Sprague-Dawley rats. Endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) protein expression and their phosphorylated forms [peNOS(Ser1177) and pnNOS(Ser1417)], 3-nitrotyrosine, reduced sulfhydryl groups (-SH), and glomerular filtration rate (GFR) were also determined. No sex differences were observed in monomeric eNOS and nNOS expression, NO, or 3-nitrotyrosine levels in nonischemic kidneys, but renal -SH content was higher in females. Ischemia increased dimeric/monomeric eNOS and nNOS ratio more in females, but the dimeric phosphorylated peNOS(Ser1177) and pnNOS(Ser1417) forms rose similarly in both sexes, indicating no sex differences in nitric oxide synthase activation. However, NO levels increased more in females than in males (6,406.0 ± 742.5 and 4,058.2 ± 272.35 nmol/l respectively, P < 0.05), together with a lower increase in peroxynitrite current (5.5 ± 0.7 vs. 12.7 ± 1.5 nA, P < 0.05) and 3-nitrotyrosine concentration, (28.7 ± 3.7 vs. 48.7 ± 3.7 nmol/mg protein, P < 0.05) in females than in males and a better preserved GFR after ischemia in females than in males (689.7 ± 135.0 and 221.4 ± 52.5 μl·min−1·g kidney wt−1, P < 0.01). Pretreatment with the antioxidants N-acetyl-l-cysteine or ebselen abolished sex differences in peroxynitrite, nitrotyrosine, and GFR, suggesting that a greater oxidative and nitrosative stress worsens renal damage in males.

scholarly journals Hypertensive female Sprague-Dawley rats require an intact nitric oxide synthase system for compensatory increases in renal regulatory T cells

2020 ◽  
Vol 319 (2) ◽  
pp. F192-F201
Author(s):  
Lindsey A. Ramirez ◽  
Ellen E. Gillis ◽  
Jacqueline B. Musall ◽  
Riyaz Mohamed ◽  
Elizabeth Snyder ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Regulatory T Cells ◽  
Female Rats ◽  
Sprague Dawley ◽  
Albumin Excretion ◽  
Sprague Dawley Rats ◽  
Oxide Synthase

We have previously shown that hypertensive female rats have more regulatory T cells (Tregs), which contribute more to blood pressure (BP) control in female versus male rats. Based on known protective properties of Tregs, the goal of the present study was to investigate the mechanisms by which female rats maintain Tregs. The present study was designed to 1) compare the impact of three hypertension models on the percentage of renal Tregs and 2) test the hypothesis that nitric oxide synthase (NOS) inhibition prevents increases in renal Tregs and exacerbates renal damage in female Sprague-Dawley rats. Rats (11–14 wk old) were randomized to one of the following four groups: control, norepinephrine (NE) infusion, angiotensin II infusion, or the NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) in drinking water. BP was measured via tail cuff. After 2 wk of treatment, kidneys were isolated and processed to measure Tregs via flow cytometric analysis and renal injury via urinary albumin excretion, plasma creatinine, and histological analyses. Hypertensive treatments increased BP in all experimental animals. Increases in BP in norepinephrine-and angiotensin II-treated rats were associated with increases in renal Tregs versus control. In contrast, l-NAME treatment decreased Tregs compared with all groups. l-NAME treatment modestly increased albumin excretion. However, plasma creatinine was comparable among the groups, and there was no histological evidence of glomerular or tubular injury. This study provides insights into the mechanisms regulating renal Tregs and supports that an intact NOS system is crucial for female rats to have BP-related increases in renal Tregs.

Variation of genes involved in oxidative and nitrosative stresses in depression

2018 ◽  
Vol 48 (1) ◽  
pp. 38-48 ◽  
Author(s):  
Paulina Wigner ◽  
Piotr Czarny ◽  
Ewelina Synowiec ◽  
Micha� Bijak ◽  
Katarzyna Białek ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Depressive Disorders ◽  
Nitrosative Stress ◽  
Nucleotide Polymorphisms ◽  
Oxidative And Nitrosative Stress ◽  
Increased Risk ◽  
Genes Encoding ◽  
Oxide Synthase ◽  
The Impact

AbstractThe dominating hypothesis among numerous hypotheses explaining the pathogenesis of depressive disorders (DD) is the one involving oxidative and nitrosative stress. In this study, we examined the association between single-nucleotide polymorphisms of the genes encoding SOD2 (superoxide dismutase 2), CAT (catalase), GPx4 (glutathione peroxidase 4), NOS1 (nitric oxide synthase 1), NOS2 (nitric oxide synthase 2), and the development of depressive disorders. Our study was carried out on the DNA isolated from peripheral blood collected from 281 depressed patients and 229 controls. Using TaqMan probes, we genotyped the following six polymorphisms: c.47T > C (p.Val16Ala) (rs4880) in SOD2, c.-89A > T (rs7943316) in CAT, c.660T > C (rs713041) in GPx4, c.-420-34221G > A (rs1879417) in NOS1, c.1823C > T (p.Ser608Leu) (rs2297518), and c.-227G > C (rs10459953) in NOS2. We found that the T/T genotype of the c.47T > C polymorphism was linked with an increased risk of depression. Moreover, the T/T genotype and T allele of c.660T > C increased the risk of DD occurrence, while the heterozygote and C allele decreased this risk. On the other hand, we discovered that the A/A genotype of c.-89A > T SNP was associated with a reduced risk of DD, while the A/T genotype increased this risk. We did not find any correlation between the genotypes/alleles of c.-420-34221G > A, c.1823C > T, and c.-227G > C, and the occurrence of DD. In addition, gene-gene and haplotype analyses revealed that combined genotypes and haplotypes were connected with the disease. Moreover, we found that sex influenced the impact of some SNPs on the risk of depression. Concluding, the studied polymorphisms of SOD2, CAT and GPx4 may modulate the risk of depression. These results support the hypothesis that oxidative and nitrosative stresses are involved in the pathogenesis of depressive disorders.

scholarly journals Doxorubicin-induced nitrosative stress is mitigated by vitamin C via the modulation of nitric oxide synthases

2017 ◽  
Vol 312 (4) ◽  
pp. C418-C427 ◽  
Author(s):  
Gauri Akolkar ◽  
Ashim K. Bagchi ◽  
Prathapan Ayyappan ◽  
Davinder S. Jassal ◽  
Pawan K. Singal
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Vitamin C ◽  
Protein Expression ◽  
Nitrosative Stress ◽  
Sprague Dawley ◽  
The Stability ◽  
Oxide Synthase ◽  
Nos Isoforms ◽  
Vit C

An increase in oxidative stress is suggested to be the main cause in Doxorubicin (Dox)–induced cardiotoxicity. However, there is now evidence that activation of inducible nitric oxide synthase (iNOS) and nitrosative stress are also involved. The role of vitamin C (Vit C) in the regulation of nitric oxide synthase (NOS) and reduction of nitrosative stress in Dox-induced cardiotoxicity is unknown. The present study investigated the effects of Vit C in the mitigation of Dox-induced changes in the levels of nitric oxide (NO), NOS activity, protein expression of NOS isoforms, and nitrosative stress as well as cytokines TNF-α and IL-10 in isolated cardiomyocytes. Cardiomyocytes isolated from adult Sprague-Dawley rats were segregated into four groups: 1) control, 2) Vit C (25 µM), 3) Dox (10 µM), and 4) Vit C + Dox. Dox caused a significant increase in the generation of superoxide radical (O2·−), peroxynitrite, and NO, and these effects of Dox were blunted by Vit C. Dox increased the expression of iNOS and altered protein expression as well as activation of endothelial NOS (eNOS). These changes were prevented by Vit C. Dox induced an increase in the ratio of monomeric/dimeric eNOS, promoting the production of O2·−, which was prevented by Vit C by increasing the stability of the dimeric form of eNOS. Vit C protected against the Dox-induced increase in TNFα as well as a reduction in IL-10. These results suggest that Vit C provides cardioprotection by reducing oxidative/nitrosative stress and inflammation via a modulation of Dox-induced increase in the NO levels and NOS activity.

Pressure natriuresis following acute and chronic inhibition of nitric oxide synthase in rats

1996 ◽  
Vol 270 (2) ◽  
pp. R469-R478 ◽  
Author(s):  
G. R. Guarasci ◽  
R. L. Kline
Keyword(s):  
Nitric Oxide ◽  
Hydrostatic Pressure ◽  
Nitric Oxide Synthase ◽  
Chronic Administration ◽  
Acute Administration ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Pressure Natriuresis ◽  
Oxide Synthase ◽  
The Relationship

Nitric oxide has been suggested to be an essential mediator of pressure natriuresis. To investigate this hypothesis, the effect of acute or chronic inhibition of nitric oxide synthase on pressure natriuresis and renal interstitial hydrostatic pressure was studied in anesthetized Sprague-Dawley rats with fixed neural and hormonal influences on the kidney. Both acute infusion (10 micrograms.kg-1.min-1 iv) and chronic administration (50 mg.kg-1.day-1 for 7 days in drinking water) of NG-nitro-L-arginine methyl ester (L-NAME) resulted in significantly increased mean arterial pressure, a 30% decrease in renal blood flow, and no change in glomerular filtration rate when compared with values in control rats. Pressure-diuresis, pressure-natriuresis, and pressure-fractional sodium excretion curves in L-NAME-treated rats were shifted to a higher pressure (by approximately 25 mmHg) when compared with those in control rats. The relationship between renal artery pressure and renal interstitial hydrostatic pressure was shifted similarly in L-NAME-treated rats. Acute administration of L-arginine completely reversed the renal effects of chronic L-NAME. These data indicate that, at the doses used in this study, both acute and chronic inhibition of nitric oxide synthase decreased the ability of the kidney to excrete sodium at least in part by a hemodynamic mechanism leading to an increased filtration fraction and a decreased renal interstitial pressure. The parallel shift of the pressure-natriuresis curve to a higher pressure suggests that nitric oxide is an important modulator but not an essential mediator of the pressure natriuresis.

scholarly journals The Effect of Ophiocephalus striatus sp. Extract on Nitric Oxide in Ischemic Stroke Model

2021 ◽  
Vol 9 (T3) ◽  
pp. 68-74
Author(s):  
Iskandar Nasution ◽  
Hasan Sjahrir ◽  
Syafruddin Ilyas ◽  
Muhammad Ichwan
Keyword(s):  
Nitric Oxide ◽  
Ischemic Stroke ◽  
Experimental Studies ◽  
Stroke Therapy ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stroke Models ◽  
Angiogenesis Process ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

BACKGROUND: One of alternative medicine in stroke therapy is Ophiocephalus striatus sp. extract. The nutrients contained in the O. striatus sp. extract, namely amino acids, fatty acids, cuprum, and zinc, are useful for the process of angiogenesis in poststroke patients through increased endothelial nitric oxide synthase. AIM: We hypothesized that there was an effect of giving O. striatus sp. extract to cerebral angiogenesis process of Sprague Dawley rats ischemic stroke models through the level of NO. METHODS: This was evidenced by conducting experimental studies on rats ischemic stroke models which were divided into five groups, (a) K (−) group (no ligation, no treatment), (b) K (+) group (ligation, no treatment), (c) P1 group (ligation, 200 mg extract), (d) P2 group (ligation, 400 mg extract), and (e) P3 group (ligation, 800 mg extract). Then blood sample was taken on day 3 to assess levels of NO. RESULTS: There was increased level of NO in P1 (p = 0.001), P2 (p < 0.001), and P3 (p < 0.001) groups compared to K (+) group. The level of NO increases along with the increasing dose of O. striatus sp. extract. Histological examination revealed that there was formation of new blood vessel in the P1, P2, and P3 groups compared to K (+) group. CONCLUSION: Our study showed that O. striatus sp. extract improves cerebral angiogenesis in rat models of ischemic stroke.

scholarly journals Curcumin Modulates Nitrosative Stress, Inflammation and DNA Damage and Protects against Ochratoxin A-Induced Hepatotoxicity and Nephrotoxicity in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1239
Author(s):  
Consiglia Longobardi ◽  
Sara Damiano ◽  
Emanuela Andretta ◽  
Francesco Prisco ◽  
Valeria Russo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Ochratoxin A ◽  
Oxidative Dna Damage ◽  
Nitrosative Stress ◽  
Antioxidant Activities ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Natural Polyphenol ◽  
Oxide Synthase

Ochratoxin A (OTA) is a fungal toxin of critical concern for food safety both for human health and several animal species, also representing a cancer threat to humans. Curcumin (CURC) is a natural polyphenol that has anti-apoptotic, anti-inflammatory, and antioxidant effects. The aim of this study was to investigate the cytoprotective effect of CURC against OTA-induced nephrotoxicity and hepatotoxicity through the study of the nitrosative stress, pro-inflammatory cytokines, and deoxyribonucleic acid (DNA) damage. Sprague Dawley rats were daily treated with CURC (100 mg/kg b.w.), OTA (0.5 mg/kg b.w), or CURC with OTA by oral gavage for 14 days. Our results demonstrated that OTA exposure was associated with significant increase of pro-inflammatory and DNA oxidative-damage biomarkers. Moreover, OTA induced the inducible nitric oxide synthase, (iNOS) resulting in increased nitric oxide (NO) levels both in kidney and liver. The co-treatment OTA + CURC counteracted the harmful effects of chronic OTA treatment by regulating inflammation, reducing NO levels and oxidative DNA damage in kidney and liver tissues. Histology revealed that OTA + CURC treatment determinates mainly an Iba1+ macrophagic infiltration with fewer CD3+ T-lymphocytes in the tissues. In conclusion, we evidenced that CURC exerted cytoprotective and antioxidant activities against OTA-induced toxicity in rats.

Glutamate induces hydroxyl radical formation in vivo via activation of nitric oxide synthase in Sprague–Dawley rats

1998 ◽  
Vol 242 (3) ◽  
pp. 131-134 ◽  
Author(s):  
Eric Lancelot ◽  
Laurent Lecanu ◽  
Marie-Louise Revaud ◽  
Roger G Boulu ◽  
Michel Plotkine ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Hydroxyl Radical ◽  
Radical Formation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Oxide Synthase
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