Oxidative Stress in a Rat Model of Obesity-Induced Hypertension

Dobrian, Anca D.; Davies, Michael J.; Schriver, Suzanne D.; Lauterio, Thomas J.; Prewitt, Russell L.

doi:10.1161/01.hyp.37.2.554

Cited by 217 publications

(199 citation statements)

References 57 publications

(58 reference statements)

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“…OX accompanying hypertension in animal models includes spontaneous hypertension, 22 renovascular hypertension, 23 deoxycorticosterone acetate-salt hypertension model 24 and obesity-related hypertension. 25 Moreover, reducing superoxide radicals by infusion of SOD significantly decreases BP in spontaneously hypertensive rats. 26 In humans, hypertension is also considered a state of OX that can be related to the development of artherosclerosis 27 and other hypertension-induced organ damage, 28 microalbuminuria.…”

Section: Discussionmentioning

confidence: 98%

Impact of the components of metabolic syndrome on oxidative stress and enzymatic antioxidant activity in essential hypertension

et al. 2006

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The objective of the present study was to analyze the impact of metabolic syndrome (MS) and its individual components on oxidative stress (OX) and on the activity of antioxidant enzymes of patients with essential hypertension. One hundred and eighty-seven hypertensives, 127 (61.9%) of them having criteria for MS according to the International Diabetes Federation criteria and 30 healthy normotensive subjects were included. OX status was assessed by measuring glutathione oxidized/glutathione reduced and reactive oxygen species-induced byproducts of lipid peroxidation, malondialdehide, and DNA damage, 8-oxo-dG genomic and mitochondrial. Antioxidant enzymatic activity of Cu/Zn extracellular-superoxide dismutase (SOD) and catalase (CAT) was measured in plasma and glutathione peroxidase 1 in hemolysad erythrocytes. In mononuclear cells, total-SOD activity, CAT and glutathione peroxidase 1, were assessed as well. The OX state in both blood and peripheral mononuclear cells observed in hypertensives were not enhanced by the addition of components of the so-called MS. Likewise, the reduction in the activity of antioxidant enzymes, both extracellular and cytoplasmic, was not affected by the presence of additional components of the MS. Neither the number of components nor the individual addition of each of them, low high-density lipoprotein, triglycerides, abdominal obesity or fasting glucose, further impact in the OX abnormalities observed in those with only hypertension in absence of other components. In conclusion, the present data indicates that contribution of MS components to the OX burden generated by high blood pressure is minimal.

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Section: Discussionmentioning

confidence: 98%

Impact of the components of metabolic syndrome on oxidative stress and enzymatic antioxidant activity in essential hypertension

et al. 2006

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“…In addition, reports indicate that redox signaling mediates central AngII-induced cardiovascular responses. [6][7][8][9][10] As obesity is associated with systemic oxidative stress, 13,33 we hypothesized that HF diet-induced obesity could increase superoxide production and/or reduce antioxidant capacity in the brain resulting in elevated SNS activity and blood pressure. In this study, we found that NOX2, the main membrane-associated subunit of NADPH oxidase, and two regulatory subunits, p47 phox and p67 phox , are significantly upregulated in response to HF feeding in the hypothalamus resulting in increased NADPH oxidase activity.…”

Section: Discussionmentioning

confidence: 99%

“…11 On the other hand, overexpression of inducible NO synthase (iNOS) in the rostral ventrolateral medulla increases oxidative stress and elevates SNS activity. 12 As obesity affects both redox signaling and NO synthesis throughout the body, [13][14][15] there is a possibility that oxidative stress and reduced bioavailability of NO in cardiovascular regulatory nuclei mediate, at least in part, sympathoexcitation and blood pressure elevation in response to obesity.…”

Section: Introductionmentioning

confidence: 99%

Effect of high-fat diet feeding on hypothalamic redox signaling and central blood pressure regulation

et al. 2009

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We examined the effect of high-fat (HF) feeding on blood pressure (BP) regulation, including hypothalamic redox signaling, as well as the changes in diurnal patterns and responses to restraint stress. Furthermore, we investigated whether HF feeding affects catecholamine and neuropeptide Y (NPY) biosynthesis in the adrenal medulla. Male obesity-prone Sprague-Dawley rats were fed with standard rat chow or 60% HF diet for 6 months. BP and heart rate (HR) were measured by telemetry, and circadian changes as well as responses to 20 min restraint stress were analyzed. Mean arterial BP was significantly elevated in HF rats both during daytime and nighttime compared with controls, whereas HR was elevated only during the day. BP and HR increased similarly in response to stress in both experimental groups; however, post-stress recovery of BP and HR were significantly delayed in HF animals. Protein levels of angiotensin II type 1 receptor (AT 1 ) and NOX2, p67 phox and p47 phox subunits of NADPH oxidase, as well as NADPH oxidase activity increased significantly in the hypothalamus with HF feeding, whereas levels of antioxidant enzymes and nitric oxide synthases remained unchanged. In addition, HF diet also elevated the adrenomedullary protein levels of tyrosine hydroxylase and NPY. This study shows that feeding obesity-prone Sprague-Dawley rats with a HF diet results in elevated BP and HR and delayed cardiovascular post-stress recovery, and that these changes are paralleled by increases in the expression and activity of NADPH oxidase in the hypothalamus without a compensatory increase in the antioxidant enzyme levels, possibly leading to superoxide-mediated sympathoexcitation and hypertension.

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“…24,26 Immunohistochemistry Formalin-fixed, paraffin-embedded sections were processed for antigen retrieval and incubated with a primary polyclonal antibody for 1:1 Cys,His,Lys-4-hydroxy-2-nonenal (HNE) adducts (Calbiochem; dilution 1:750). The slides were stained with reagents from a commercially available kit (Immuno Pure Metal Enhanced DAB substrate kit, Pierce).…”

Section: Bp Measurementsmentioning

confidence: 99%

“…27 RNA (1 g) was reverse-transcribed (RT) and amplified by polymerase chain reaction (PCR) as previously described. 26 The following pairs of forward and reverse primers were used: PPAR␥1,2, 5Ј-TCCGTG ATGGAAGACCACTC-3Ј and 5Ј-CCCTTGCATCCTTCACAAGC-3Ј; and ␤-actin, 5Ј-CGTAAAGACCTCTATGCCAA-3Ј and 5Ј-CTCCAGTGCCAAGGTC TGAA-3Ј. The neuronal (nNOS) and endothelial (eNOS) NO synthase primers were described previously.…”

Section: Rna Isolation and Rt-pcrmentioning

confidence: 99%

Pioglitazone Prevents Hypertension and Reduces Oxidative Stress in Diet-Induced Obesity

et al. 2004

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Abstract-The objective of this study was to determine the effect of pioglitazone on blood pressure (BP) and oxidative balance in obese, hypertensive, Sprague-Dawley rats and to identify some of the molecular mechanisms involved. After 12 weeks of a moderately high-fat diet, rats diverged into obesity-prone (OP) and obesity-resistant (OR) groups (nϭ6 per group). At the end of the diet, peroxisome proliferator activated receptor-␥ (PPAR␥) mRNA expression and activity in the renal cortex and medulla of OP rats were significantly lower compared with that in OR rats. Pioglitazone treatment increased PPAR␥ expression and activity in OP rats, suggesting a possible direct ligand-related effect of pioglitazone. As opposed to the untreated OP group, which showed moderate hypertension (systolic BPϭ159Ϯ5.3 mm Hg) after 12 weeks, pioglitazone-treated rats were normotensive (systolic BPϭ123.9Ϯ2.7 mm Hg). Insulin production was reduced by 2-fold in the OP group treated with pioglitazone. Urinary isoprostanes and renal lipid peroxides were also reduced in OP rats treated with pioglitazone compared with untreated counterparts. Also, expression of p47phox and gp91phox, both increased in OP versus OR rats, was reduced in the former by pioglitazone treatment. In addition, pioglitazone treatment increased nitrate/nitrite excretion and expression of renal endothelial and neuronal nitric oxide synthase. Collectively, the results show that pioglitazone treatment prevented hypertension and renal oxidative stress both by reducing free-radical production and by increasing nitric oxide production/availability. Key Words: kidney Ⅲ oxidative stress Ⅲ free radicals Ⅲ nitric oxide Ⅲ vitamins O besity is a widespread and increasingly prevalent condition associated with a large number of comorbid diseases, one of the most important of which is obesityinduced hypertension. A pleiotropic class of molecules involved in regulation of gene expression in a variety of metabolic and cardiovascular conditions is the peroxisome proliferator-activated receptors (PPARs). PPARs are ligandactivated transcription factors that form heterodimers with the 9-cis retinoic acid receptor RXR␣. 1 PPAR␥ is one of the three PPAR isoforms and is one of the major regulators of adipogenesis. 2 In addition, PPAR␥ exerts pleiotropic effects on blood pressure, lipid metabolism, and insulin action.Recent genetic analysis showed that 2 dominant-negative mutations in PPAR␥ were associated with severe hypertension in humans. 3,4 Consistent with these findings, thiazolidinendiones, the insulin-sensitizer drugs (pioglitazone, rosiglitazone) that are also high-affinity PPAR␥ ligands, 5 have been shown to lower blood pressure (BP) in a variety of hypertensive animal models 6 -8 as well as in diabetic and nondiabetic, 9 hypertensive humans. However, the mechanism underlying the antihypertensive effects of PPAR␥ agonists is not known. PPAR␥ and RXR have been found constitutively expressed in the inner medullary collecting ducts, thick ascending limb, glomerulus, and renal medullary mic...

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Oxidative Stress in a Rat Model of Obesity-Induced Hypertension

Cited by 217 publications

References 57 publications

Impact of the components of metabolic syndrome on oxidative stress and enzymatic antioxidant activity in essential hypertension

Impact of the components of metabolic syndrome on oxidative stress and enzymatic antioxidant activity in essential hypertension

Effect of high-fat diet feeding on hypothalamic redox signaling and central blood pressure regulation

Pioglitazone Prevents Hypertension and Reduces Oxidative Stress in Diet-Induced Obesity

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