Pregnant rats treated with a high-fat/prooxidant Western diet with ANG II and TNF-α are resistant to elevations in blood pressure and renal oxidative stress

Oxidative stress and inflammation are risk factors for hypertension in pregnancy. Here, we examined the 24-h mean arterial pressure (MAP) via telemetry and the nitric oxide (NO) and redox systems in the kidney cortex, medulla, and aorta of virgin and pregnant rats treated with a high-fat/prooxidant Western diet (HFD), ANG II, and TNF-α. Female Sprague-Dawley rats were given a normal diet (ND) or a HFD for 8 wk before mating. Day 6 of pregnancy and age-matched virgins were implanted with minipumps infusing saline or ANG II (150 ng·kg−1·min−1) + TNF-α (75 ng/day) for 14 days. Groups consisted of Virgin + ND + Saline (V+ND) ( n = 7), Virgin + HFD +ANG II and TNF-α (V+HFD) ( n = 7), Pregnant + ND + Saline (P+ND) ( n = 6), and Pregnant + HFD + ANG II and TNF-α (P+HFD) ( n = 8). After day 6 of minipump implantation, V+HFD rats displayed an increase in MAP on days 7, 8, and 10–15 vs. V+ND rats. P+HFD rats, after day 6 of minipump implantation, showed an increase in MAP only on day 7 vs. P+ND rats. P+HFD rats had a normal fall in 24-h MAP, hematocrit, plasma protein concentration, and osmolality at late pregnancy. No change in kidney cortex, medulla, or aortic oxidative stress in P+HFD rats. P+HFD rats displayed a decrease in nNOSβ abundance, but no change in kidney cortex NOxcontent vs. P+ND rats. Pregnant rats subjected to a chronic HFD and prooxidant and proinflammatory insults have a blunted increase in 24-h MAP and renal oxidative stress. Our data suggest renal NO bioavailability is not altered in pregnant rats treated with a HFD, ANG II, and TNF-α.

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Serelaxin reduces oxidative stress and asymmetric dimethylarginine in angiotensin II-induced hypertension

AJP Renal Physiology ◽

10.1152/ajprenal.00407.2014 ◽

2014 ◽

Vol 307 (12) ◽

pp. F1355-F1362 ◽

Cited By ~ 36

Author(s):

Jennifer M. Sasser ◽

Mark W. Cunningham ◽

Chris Baylis

Keyword(s):

Oxidative Stress ◽

Asymmetric Dimethylarginine ◽

Oxidation Products ◽

No Oxidation ◽

Kidney Cortex ◽

High Dose ◽

Protective Effects ◽

Ang Ii ◽

Sprague Dawley ◽

Induced Hypertension

Recent findings suggest the therapeutic action of relaxin during hypertension is dependent on nitric oxide synthase (NOS) activation; however, the mechanisms underlying the beneficial effects of relaxin on the NOS system have not been fully elucidated. We hypothesized that the protective effects of relaxin include reducing both oxidative stress and the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA). We examined the effect of Serelaxin [human recombinant relaxin-2 (RLX)] in male Sprague-Dawley rats given high-dose angiotensin (ANG) II (400 ng·kg−1·min−1 sc) for 6 wk or shams. RLX was administered (4 μg/h sc) to half of the rats in each group after 2 wk of ANG II for the remaining 4 wk. ANG II induced hypertension and proteinuria, reduced NO oxidation products (NOx), and increased oxidative stress (NADPH oxidase activity, thiobarbituric acid-reactive substances, and 8-isoprostane excretion) and plasma ADMA. While RLX had no effect on sham rats, RLX attenuated the ANG II-dependent hypertension (165 ± 5 vs. 135 ± 13 mmHg, P < 0.05) and proteinuria at 6 wk (62 ± 6 vs. 41 ± 4 mg·day−1·100 g−1, P < 0.05) and normalized oxidative stress and circulating ADMA, in association with restored NOx excretion and kidney cortex NOx. We found that RLX had no impact on the ADMA-regulatory enzymes protein arginine methyltransferase and dimethylarginine-dimethylaminohydrolase (DDAH). Furthermore, RLX treatment did not increase DDAH activity in kidney cortex or liver. These data suggest that benefits of RLX treatment include reduced ADMA levels and increased NO bioavailability, possibly due to its antioxidant effects.

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Osthol Ameliorates Kidney Damage and Metabolic Syndrome Induced by a High-Fat/High-Sugar Diet

International Journal of Molecular Sciences ◽

10.3390/ijms22052431 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2431

Author(s):

Fernando E. García-Arroyo ◽

Guillermo Gonzaga-Sánchez ◽

Edilia Tapia ◽

Itzel Muñoz-Jiménez ◽

Lino Manterola-Romero ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Western Diet ◽

Kidney Damage ◽

Kidney Cortex ◽

Tubular Damage ◽

Related Factor ◽

Lipogenic Enzymes ◽

High Fat ◽

High Sugar

Excessive intake of fructose results in metabolic syndrome (MS) and kidney damage, partly mediated by its metabolism by fructokinase-C or ketohexokinase-C (KHK-C). Osthol has antioxidant properties, is capable of regulating adipogenesis, and inhibits KHK-C activity. Here, we examined the potential protective role of osthol in the development of kidney disease induced by a Western (high-fat/high-sugar) diet. Control rats fed with a high-fat/high-sugar diet were compared with two groups that also received two different doses of osthol (30 mg/kg/d or 40 mg/kg/d body weight BW). A fourth group served as a normal control and received regular chow. At the end of the follow-up, kidney function, metabolic markers, oxidative stress, and lipogenic enzymes were evaluated. The Western diet induced MS (hypertension, hyperglycemia, hypertriglyceridemia, obesity, hyperuricemia), a fall in the glomerular filtration rate, renal tubular damage, and increased oxidative stress in the kidney cortex, with increased expression of lipogenic enzymes and increased kidney KHK expression. Osthol treatment prevented the development of MS and ameliorated kidney damage by inhibiting KHK activity, preventing oxidative stress via nuclear factor erythroid 2-related factor (Nrf2) activation, and reducing renal lipotoxicity. These data suggest that the nutraceutical osthol might be an ancillary therapy to slow the progression of MS and kidney damage induced by a Western diet.

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Histidine supplementation alleviates inflammation in the adipose tissue of high-fat diet-induced obese rats via the NF-κB- and PPARγ-involved pathways

British Journal Of Nutrition ◽

10.1017/s0007114514001056 ◽

2014 ◽

Vol 112 (4) ◽

pp. 477-485 ◽

Cited By ~ 18

Author(s):

Xiaowei Sun ◽

Rennan Feng ◽

Yanchuan Li ◽

Song Lin ◽

Wei Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

High Fat Diet ◽

Low Grade ◽

Obese Women ◽

Sprague Dawley ◽

High Fat ◽

Tnf Α ◽

Obese Rats ◽

And Oxidative Stress

Obesity is considered to be accompanied by a chronic low-grade inflammatory state that contributes to the occurrence of many chronic diseases. Our previous study has demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women. However, the in vivo potential mechanisms are not known. The present study was conducted to investigate the mechanisms underlying the effects of histidine on inflammation in a high-fat diet (HFD)-induced female obese rat model. An obese model was established in female Sprague–Dawley rats by HFD feeding for 8 weeks and followed by histidine supplementation for another 4 weeks. The results revealed that HFD-increased body weight and HFD-lowered serum histidine concentrations were significantly reversed by histidine supplementation (P< 0·05). In addition, the serum concentrations of TNF-α, IL-6, C-reactive protein (CRP) and malondialdehyde were significantly reduced and those of superoxide dismutase (SOD) were significantly increased by histidine supplementation when compared with those in obese rats (P< 0·05). Correspondingly, the mRNA expressions of TNF-α, IL-6 and CRP in the adipose tissue were significantly down-regulated and that of CuZnSOD was significantly up-regulated by histidine supplementation (P< 0·05). Histidine supplementation significantly reduced the HFD-induced translocation of NF-κB p65 into the nucleus (P= 0·032) by reducing the phosphorylation of the inhibitor of κBα in the adipose tissue. The results also revealed that the expression of adiponectin was markedly increased both in the serum and in the adipose tissue after histidine supplementation, accompanied by the activation of PPARγ (P= 0·021). These findings indicate that histidine is an effective candidate for ameliorating inflammation and oxidative stress in obese individuals via the NF-κB- and PPARγ-involved pathways.

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Galangin Resolves Cardiometabolic Disorders through Modulation of AdipoR1, COX-2, and NF-κB Expression in Rats Fed a High-Fat Diet

Antioxidants ◽

10.3390/antiox10050769 ◽

2021 ◽

Vol 10 (5) ◽

pp. 769

Author(s):

Patoomporn Prasatthong ◽

Sariya Meephat ◽

Siwayu Rattanakanokchai ◽

Juthamas Khamseekaew ◽

Sarawoot Bunbupha ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiac Tissue ◽

Sprague Dawley ◽

High Fat ◽

Impaired Liver Function ◽

Impaired Liver ◽

Cardiometabolic Disorders ◽

Cox 2 ◽

Factor Α ◽

And Oxidative Stress

Galangin is a natural flavonoid. In this study, we evaluated whether galangin could alleviate signs of metabolic syndrome (MS) and cardiac abnormalities in rats receiving a high-fat (HF) diet. Male Sprague–Dawley rats were given an HF diet plus 15% fructose for four months, and they were fed with galangin (25 or 50 mg/kg), metformin (100 mg/kg), or a vehicle for the last four weeks. The MS rats exhibited signs of MS, hypertrophy of adipocytes, impaired liver function, and cardiac dysfunction and remodeling. These abnormalities were alleviated by galangin (p < 0.05). Interleukin-6 and tumor necrosis factor-α concentrations and expression were high in the plasma and cardiac tissue in the MS rats, and these markers were suppressed by galangin (p < 0.05). These treatments also alleviated the low levels of adiponectin and oxidative stress induced by an HF diet in rats. The downregulation of adiponectin receptor 1 (AdipoR1) and cyclooxygenase-2 (COX-2) and the upregulation of nuclear factor kappa B (NF-κB) expression were recovered in the galangin-treated groups. Metformin produced similar effects to galangin. In conclusion, galangin reduced cardiometabolic disorders in MS rats. These effects might be linked to the suppression of inflammation and oxidative stress and the restoration of AdipoR1, COX-2, and NF-κB expression.

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Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat

AJP Renal Physiology ◽

10.1152/ajprenal.00252.2006 ◽

2007 ◽

Vol 292 (2) ◽

pp. F861-F867 ◽

Cited By ~ 17

Author(s):

Melvin R. Hayden ◽

Nazif A. Chowdhury ◽

Shawna A. Cooper ◽

Adam Whaley-Connell ◽

Javad Habibi ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Systolic Blood Pressure ◽

Proximal Tubule ◽

Structural Damage ◽

Kidney Tissue ◽

Proximal Tubule Cell ◽

Ang Ii ◽

Sprague Dawley ◽

Sprague Dawley Rats

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5–8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6–7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-d-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and ×60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats ( P < 0.05) correlated strongly with albuminuria ( r2 = 0.83) and moderately with MDA ( r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats ( P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-d-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.

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Abstract 382: Anti-MAA Antibodies in Sprague Dawley Rats are Increased in Response to a High Fat Western Diet

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a382 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Michael J Duryee ◽

Anand Dusad ◽

Scott W Shurmur ◽

Michael D Johnston ◽

Robert P Garvin ◽

...

Keyword(s):

High Fat Diet ◽

Normal Diet ◽

Western Diet ◽

Sprague Dawley ◽

High Fat ◽

Sprague Dawley Rats ◽

Stable Plaque ◽

Circulating Antibodies ◽

Modified Proteins ◽

Progression Of Atherosclerosis

Introduction Malondialdehyde/Acetaldehyde (MAA) modified proteins have been suggested to play a role in the development/progression of atherosclerosis. Circulating antibodies directed against these proteins have recently been shown to be associated with the severity of the disease. More specifically, the isotype of the antibody to MAA correlated with either an acute MI (IgG) or stable plaque formation (IgA) formation. MAA is thought to form as a result of the oxidation of fat(s) and thus the concentration and antibody response should reflect the amount of fat in the diet. Objective The purpose of this study was to evaluate the antibody responses to MAA modified proteins following immunization and high fat western diet feeding in rats. Methods Male Sprague Dawley rats were immunized with MAA-modified protein weekly for 5 weeks and then assayed for antibodies to these proteins. Animals were then separated into the following groups: chow sham, chow MAA immunized, high fat sham, and high fat MAA immunized. The high fat animals were fed a Western diet with 2-thiouracil for 12 weeks, bled every 3 weeks, and serum assayed for the presence of circulating MAA antibodies. Results Prior to feeding with high fat diet, rats immunized with MAA-modified protein had a significant increase (P<0.001) in serum antibodies directed against these modified proteins compared to controls (N of 4 per group). Following feeding of high fat diet antibody concentrations increased 6 fold in the high fat MAA immunized group compared to the chow MAA immunized group (P<0.05). Antibodies in the high fat sham and chow sham had only minimal increases in antibodies to these proteins. Conclusions These data demonstrate that following immunization with MAA-modified proteins, circulating antibodies are produced that increase following consumption of a high fat Western diet. It suggests that MAA-modified proteins are produced at low levels following normal diet, producing antibodies which act as a normal clearance method for altered protein. When high fat consumption increases these antibody levels are increased in response to the oxidative stress. Implications Use of these antibodies as a biomarker in the future may help predict the onset or progression of atherosclerosis.

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Angiotensin II-mediated biphasic regulation of proximal tubular Na+/H+ exchanger 3 is impaired during oxidative stress

AJP Renal Physiology ◽

10.1152/ajprenal.00121.2011 ◽

2011 ◽

Vol 301 (2) ◽

pp. F364-F370 ◽

Cited By ~ 30

Author(s):

Anees Ahmad Banday ◽

Mustafa F. Lokhandwala

Keyword(s):

Oxidative Stress ◽

Protein Kinase ◽

Tap Water ◽

Buthionine Sulfoximine ◽

Inhibitory Effect ◽

Ang Ii ◽

Sprague Dawley ◽

High Concentration ◽

Nitric Oxide Signaling ◽

Proximal Tubular

Angiotensin (ANG) II via AT1 receptors (AT1Rs) maintains sodium homeostasis by regulating renal sodium transporters including Na+/H+ exchanger 3 (NHE3) in a biphasic manner. Low-ANG II concentration stimulates whereas high concentrations inhibit NHE3 activity. Oxidative stress has been shown to upregulate AT1R function that could modulate the ANG II-mediated NHE3 regulation. This study was designed to identify the signaling pathways responsible for ANG II-mediated biphasic regulation of proximal tubular NHE3 and the effect of oxidative stress on this phenomenon. Male Sprague-Dawley rats were chronically treated with a pro-oxidant l-buthionine sulfoximine (BSO) with and without an antioxidant tempol in tap water for 3 wk. BSO-treated rats exhibited oxidative stress and high blood pressure. At low concentration (1 pM) ANG II increased NHE3 activity in proximal tubules from all animals. However, in BSO-treated rats, the stimulation was more robust and was normalized by tempol treatment. ANG II (1 pM)-mediated NHE3 activation was abolished by AT1R blocker, intracellular Ca2+ chelator, and inhibitors of phospholipase C (PLC) and Ca2+-dependent calmodulin (CaM) but it was insensitive to Giα and protein kinase C inhibitors or AT2R antagonist. A high concentration of ANG II (1 μM) inhibited NHE3 activity in control and tempol-treated rats. However, in BSO-treated rats, ANG II (1 μM) continued to induce NHE3 stimulation. Tempol restored the inhibitory effect of ANG II (1 μM) in BSO-treated rats. The inhibitory effect of ANG II (1 μM) involved AT1R-dependent, cGMP-dependent protein kinase (PKG) activation and was independent of AT2 receptor and nitric oxide signaling. We conclude that ANG II stimulates NHE3 via AT1R-PLC-CaM pathway and inhibits NHE3 by AT1R-PKG activation. Oxidative stress impaired ANG II-mediated NHE3 biphasic response in that stimulation was observed at both high- and low-ANG II concentration.

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IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

Cellular Physiology and Biochemistry ◽

10.1159/000445572 ◽

2016 ◽

Vol 38 (6) ◽

pp. 2163-2172 ◽

Cited By ~ 17

Author(s):

Xiaorong Hu ◽

Ruisong Ma ◽

Jiajia Lu ◽

Kai Zhang ◽

Weipan Xu ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Responses ◽

Tunel Staining ◽

Ischemia And Reperfusion ◽

Stress Reactions ◽

Sprague Dawley ◽

Sod Activity ◽

Myocardial Ischemia And Reperfusion ◽

Tnf Α ◽

And Oxidative Stress

Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R) injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P < 0.05). Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-α and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R (all P<0.05). IL-23 had no effect on the expression of HMGB1 (p > 0.05). All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.

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Abstract 1476: Angiotensin II Induced Hypertrophic Response And Oxidative Stress Is Attenuated In Mice Lacking The Gene For Tnf-α

Circulation ◽

10.1161/circ.116.suppl_16.ii_304-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Srinivas Sriramula ◽

Nithya Mariappan ◽

Elizabeth McILwain ◽

Joseph Francis

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

Cardiac Hypertrophy ◽

Collagen Type ◽

Resonance Spectroscopy ◽

Type I ◽

Ang Ii ◽

Hypertrophic Response ◽

Tnf Α ◽

And Oxidative Stress

Tumor necrosis factor-alpha (TNF-α) and angiotensin II (Ang II) play an important role in the pathophysiology of cardiovascular disease in part by inducing the cardiac hypertrophic response and oxidative stress. Recently we demonstrated that angiotensin induced hypertensive response is attenuated in mice lacking the gene for TNF-α. In this study, we examined whether Ang II induced cardiac hypertrophy and increased oxidative stress is mediated through TNF-α. Methods and results: Male TNF-α (−/−) and age matched control (WT) mice were subcutaneously implanted with osmotic minipumps containing Ang II (1 μg/kg/min) or saline for 14 days. Human recombinant TNF-α was injected in one group of TNF-α (−/−) mice (10 μg/kg/day) for 14 days. In WT+Ang mice, a temporal increase in blood pressure was observed during the study as measured by radio telemetry transmitters. At the end of the study, echocardiography revealed an increase in thickness and dimensions of left ventricle (LV) and decreased fractional shortening (%FS) in WT+Ang mice. Real time RT-PCR showed that Ang II- infusion resulted in an increase in heart/bodyweight ratio and of cardiac hypertrophy markers ANP and BNP, and profibrotic genes Collagen Type I, Collagen Type II, and TGF-β in WT mice. Electron Spin resonance spectroscopy revealed an increase in total ROS, superoxide and peroxynitrite in the WT+ANG mice when compared to control WT mice. However, these changes were all attenuated in TNF-α (−/−)+Ang mice. Ang II infusion also increased significantly the mRNA expression of gp91Phox, NOX-1, NOX-4 and AT1R in the LV of WT mice, but not in TNF-α (−/−) mice. Interestingly, injection of TNF-α in the TNF-α (−/−) mice, treated with Ang II resulted in increased cardiac hypertrophy and oxidative stress. Conclusions: Findings from the present study suggest that TNF-α plays an important role in the development of cardiac hypertrophy and oxidative stress in Ang II-induced hypertension.

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Oxidative Stress in a Rat Model of Obesity-Induced Hypertension

Hypertension ◽

10.1161/hyp.36.suppl_1.685-e ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 685-686

Author(s):

Anca D Dobrian ◽

Michael J Davies ◽

Suzanne D Schriver ◽

Thomas J Lauterio ◽

Russell L Prewitt

Keyword(s):

Oxidative Stress ◽

Rat Model ◽

Colorimetric Method ◽

Systolic Pressure ◽

Fold Increase ◽

Kidney Cortex ◽

Strong Increase ◽

No Production ◽

Sprague Dawley ◽

Enos Expression

45 The mechanisms underlying the development of hypertension in obesity are not yet fully understood. We recently reported the development of hypertension in a rat model of diet-induced obesity (Dobrian AD et al Hypertension 2000;35: in press). When Sprague-Dawley rats (n=60) are fed a moderately high fat diet(32kcal% fat) for 10-16 weeks, about half of them develop obesity (obesity-prone (OP) and mild hypertension (153±3.4 mmHg systolic pressure), whereas the other half (obesity-resistant, OR) maintains body weight equivalent to low fat control (C) and are normotensive. We examined the potential role of oxidative stress in the development of hypertension in this model. Lipid peroxides measured as thiobarbituric acid reactive substances (TBARS) are showing a significant increase in the LDL fraction of OP rats (2.8±0.32 nmol MDA/mg protein) compared to OR and C (0.9±0.3 nmol MDA/mg protein). Also, aortic and kidney TBARS showed a significant 3- and 5- fold increase in OP rats after 16 weeks of diet (3.3±0.44 aorta and 6.7±0.52 nmol MDA/mg protein kidney) vs OR. In addition, superoxide generation by aortic rings, measured by lucigenin (25μM) luminescence showed a 2-fold increase in the OP group (4325.6±174 RLU/15 min/mg DNA X10 5 ) compared to both OR and C. Plasma renin activity was 2-fold increased in OP vs both OR and control groups.The urine nitrate/nitrite measured by LDH colorimetric method showed a 1.8-fold decrease in OP rats (2.4±0.17 μmoles) compared to OR. A similar 1.6-fold decrease was found for plasma nitrate/nitrite in OP rats vs OR and C. However, eNOS expression assessed by semiquantitative RT-PCR showed a strong increase in the OP rats vs OR and controls in both kidney cortex(eNOS/β-actin ratio of 0.78±0.21 in OP vs 0.32±0.16 in OR)and medulla(0.86±0.18 in OP vs 0.36±0.14 in OR), suggesting a possible shift toward superoxide vs NO production by the eNOS enzyme.Also, eNOS expression was increased ∼4.8-fold in the thoracic aorta of OP compared to OR rats. Collectively, data show a decreased NO production in OP animals, due in part to the increased oxidative stress, possibly generated by the activation of renin-angiotensin system and increased eNOS expression.

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