Reduced Dietary Selenium Impairs Vascular Function by Increasing Oxidative Stress in Sprague-Dawley Rat Aortas

Little is known about the consequences of maternal copper (Cu) deficiency on the vascular function of offspring or on perpetuation of vascular effects to a second generation. We examined vascular functional responses in mesenteric arteries from Cu-deficient Sprague-Dawley rat dams and from offspring directly exposed to maternal Cu deficiency during development and lactation and perpetuation of the effects in a second generation of offspring. Dams were fed a diet with marginal (1 mg Cu/kg) or adequate (6 mg Cu/kg) Cu for 3 weeks before conception and throughout pregnancy and lactation periods. Half of the first generation (F1) litters were cross-fostered. At reproductive maturity, F1 pairs were bred within groups resulting in second generation (F2) offspring. At 9 weeks of age, mesenteric artery (200 μm) isometric tension was determined in response to vasoconstrictors and vasorelaxants using a small artery wire myograph. Cu deficiency did not alter the vascular function in dams. In F1 offspring, increased responsiveness to potassium chloride in male offspring was due to direct exposure to maternal Cu deficiency in the birth mother, while enhanced endothelium-dependent relaxation responses in female offspring resulted from postnatal exposure to maternal Cu deficiency. Increased endothelium independent and decreased endothelium-dependent relaxation responses were identified in F2 Cu-deficient male offspring. These data indicate that exposure to maternal Cu deficiency during critical windows of development alter the vascular function across two generations of offspring.

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Assessment of the antioxidant potential of alcoholic extract of Garcinia kola seed in alcohol induced testicular oxidative stress in sprague-dawley rat

Nigerian Journal of Health and Biomedical Sciences ◽

10.4314/njhbs.v5i1.11571 ◽

2006 ◽

Vol 5 (1) ◽

Author(s):

AO Okanlawon ◽

AO Akpantah ◽

OA Olabiyi ◽

AA Oremosu ◽

CC Noronha

Keyword(s):

Oxidative Stress ◽

Antioxidant Potential ◽

Alcoholic Extract ◽

Sprague Dawley ◽

Sprague Dawley Rat

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Endothelial-specific CYP4A2 overexpression leads to renal injury and hypertension via increased production of 20-HETE

AJP Renal Physiology ◽

10.1152/ajprenal.00364.2009 ◽

2009 ◽

Vol 297 (4) ◽

pp. F875-F884 ◽

Cited By ~ 38

Author(s):

Kazuyoshi Inoue ◽

Komal Sodhi ◽

Nitin Puri ◽

Katherine H. Gotlinger ◽

Jiang Cao ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Endothelial Dysfunction ◽

Renal Injury ◽

Vascular Function ◽

Vascular Endothelial ◽

Sprague Dawley ◽

Sd Rats ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

We have previously reported that adenoviral-mediated delivery of cytochrome P-450 (CYP) 4A2, which catalyzes the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), results in endothelial dysfunction and hypertension in Sprague-Dawley (SD) rats (Wang JS, Singh H, Zhang F, Ishizuka T, Deng H, Kemp R, Wolin MS, Hintze TH, Abraham NG, Nasjletti A, Laniado-Schwartzman M. Circ Res 98: 962–969, 2006). In this study, we targeted the vascular endothelium by using a lentivirus construct expressing CYP4A2 under the control of the endothelium-specific promoter VE-cadherin (VECAD-4A2) and examined the effect of long-term CYP4A2 overexpression on blood pressure and kidney function in SD rats. A bolus injection of VECAD-4A2 increased blood pressure ( P < 0.001) by 26, 36, and 30 mmHg 10, 20, and 30 days postinjection, respectively. Arteries from VECAD-4A2-transduced rats produced increased levels of 20-HETE ( P < 0.01), expressed lower levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) ( P < 0.05), generated higher levels of superoxide anion, and displayed decreased relaxing responsiveness to acetylcholine ( P < 0.05). Proteinuria increased by twofold in VECAD-4A2-transduced rats compared with controls. Treatment of VECAD-4A2-transduced rats with HET0016, an inhibitor of 20-HETE biosynthesis, not only attenuated the increase in blood pressure ( P < 0.05) but also improved vascular function (acetylcholine-induced relaxations) and reduced plasma creatinine and proteinuria. HET0016 treatment decreased oxidative stress and increased the phosphorylated state of key proteins that regulate endothelial function, including eNOS, AKT, and AMPK. Collectively, these findings demonstrate that augmentation of vascular endothelial 20-HETE levels results in hypertension, endothelial dysfunction, and renal injury, which is offset by HET0016 through a reduction in vascular 20-HETE coupled with a lessening of oxidative stress and the amplification of pAKT, pAMPK, and p-eNOS levels leading to normalization of endothelial responses.

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

BioMed Research International ◽

10.1155/2019/3708497 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 2

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.

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