NADPH Oxidases, Reactive Oxygen Species, and Hypertension

Paravicini, Tamara M.; Touyz, Rhian M.

doi:10.2337/dc08-s247

Cited by 634 publications

(474 citation statements)

References 161 publications

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“…The major sources of ROS at vascular level are NADPH oxidase and mitochondria 46, 47, 48. Our data show for the first time that BCAA produce functional effects on the vascular wall.…”

Section: Discussionmentioning

confidence: 58%

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Zhenyukh

González‐Amor

Rodrigues-Díez

et al. 2018

J Cellular Molecular Medi

112

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Branched‐chain amino acids (BCAA: leucine, isoleucine and valine) are essential amino acids implicated in glucose metabolism and maintenance of correct brain function. Elevated BCAA levels can promote an inflammatory response in peripheral blood mononuclear cells. However, there are no studies analysing the direct effects of BCAA on endothelial cells (ECs) and its possible modulation of vascular function. In vitro and ex vivo studies were performed in human ECs and aorta from male C57BL/6J mice, respectively. In ECs, BCAA (6 mmol/L) increased eNOS expression, reactive oxygen species production by mitochondria and NADPH oxidases, peroxynitrite formation and nitrotyrosine expression. Moreover, BCAA induced pro‐inflammatory responses through the transcription factor NF‐κB that resulted in the release of intracellular adhesion molecule‐1 and E‐selectin conferring endothelial activation and adhesion capacity to inflammatory cells. Pharmacological inhibition of mTORC1 intracellular signalling pathway decreased BCAA‐induced pro‐oxidant and pro‐inflammatory effects in ECs. In isolated murine aorta, BCAA elicited vasoconstrictor responses, particularly in pre‐contracted vessels and after NO synthase blockade, and triggered endothelial dysfunction, effects that were inhibited by different antioxidants, further demonstrating the potential of BCAA to induce oxidative stress with functional impact. In summary, we demonstrate that elevated BCAA levels generate inflammation and oxidative stress in ECs, thereby facilitating inflammatory cells adhesion and endothelial dysfunction. This might contribute to the increased cardiovascular risk observed in patients with elevated BCAA blood levels.

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“…The major sources of ROS at vascular level are NADPH oxidase and mitochondria 46, 47, 48. Our data show for the first time that BCAA produce functional effects on the vascular wall.…”

Section: Discussionmentioning

confidence: 58%

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Zhenyukh

González‐Amor

Rodrigues-Díez

et al. 2018

J Cellular Molecular Medi

112

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“…Our current study shows for the first time that canola oil intake with salt reduces NADPH oxidase subunits and SOD isoforms in the aorta of SHRSP rats after 25 days of feeding. Evidence has shown that ·O 2 ˉ generated from NAPDP oxidase is increased in hypertension [16]. In addition, Kitiyakara et al found that salt intake in Sprague-Dawley rats lead to an increase in ·O 2 ˉ production [23].…”

Section: Discussionmentioning

confidence: 99%

“…In hypertensive patients, vascular smooth muscle cells (VSMCs) from resistance arteries have increased ROS generation, and this increase is linked to NADPH oxidase [16]. Evidence has shown that in SHR and SHRSP rats there was an enhanced production of superoxide (·O 2 ˉ) derived from NADPH oxidase, and this was associated with the upregulation of p22 phox mRNA expression in the aorta [14,17].…”

Section: Introductionmentioning

confidence: 99%

“…There are three isoforms of SOD which have been identified and include a cytosolic copper/zinc-containing SOD (CuZn-SOD), mitochondrial SOD (Mn-SOD), and extracellular SOD (Ec-SOD). The main vascular SOD is Ec-SOD and is produced and secreted by VSMCs [15,16]. Evidence has shown that in atherosclerotic vessels Ec-SOD expression is increased in apoE-deficient mice, a mouse model of atherosclerosis [19].…”

Section: Introductionmentioning

confidence: 99%

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The effect of short-term canola oil ingestion on oxidative stress in the vasculature of stroke-prone spontaneously hypertensive rats

et al. 2011

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BackgroundThis study aimed to determine if 25 days of canola oil intake in the absence of excess dietary salt or together with salt loading affects antioxidant and oxidative stress markers in the circulation. A further aim was to determine the mRNA expression of NADPH oxidase subunits and superoxide dismutase (SOD) isoforms in the aorta of stroke-prone spontaneously hypertensive (SHRSP) rats.MethodsMale SHRSP rats, were fed a defatted control diet containing 10% wt/wt soybean oil or a defatted treatment diet containing 10% wt/wt canola oil, and given tap water or water containing 1% NaCl. Blood was collected at the end of study for analysis of red blood cell (RBC) antioxidant enzymes, RBC and plasma malondialdehyde (MDA), plasma 8-isoprostane and plasma lipids. The aorta was removed and the mRNA expression of NOX2, p22phox, CuZn-SOD, Mn-SOD and EC-SOD were determined.ResultsIn the absence of salt, canola oil reduced RBC SOD and glutathione peroxidase, and increased total cholesterol and LDL cholesterol compared with soybean oil. RBC glutathione peroxidase activity was significantly lower in both the salt loaded groups compared to the soybean oil only group. In addition, RBC MDA and plasma HDL cholesterol were significantly higher in both the salt loaded groups compared to the no salt groups. Plasma MDA concentration was higher and LDL cholesterol concentration lower in the canola oil group loaded with salt compared to the canola oil group without salt. The mRNA expression of NADPH oxidase subunits and SOD isoforms were significantly reduced in the canola oil group with salt compared to canola oil group without salt.ConclusionIn conclusion, these results indicate that canola oil reduces antioxidant status and increases plasma lipids, which are risk factors for cardiovascular disease. However, canola oil in combination with salt intake increased MDA, a marker of lipid peroxidation and decreased NAPDH oxidase subunits and aortic SOD gene expression.

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“…ROS are naturally produced as a result of oxygen metabolism and include free radicals, like superoxide anion (O 2 .-) and hydroxyl radical ( . OH), and nonradicals, namely H 2 O 2 [6]. The association between oxidative stress and hypertension has been verified in several models of hypertension (reviewed in [6]), such as the SHR, which is a well characterized and extensively used genetic model for studying essential hypertension.…”

Section: Introductionmentioning

confidence: 96%

Increased responsiveness to JNK1/2 mediates the enhanced H2O2-induced stimulation of Cl−/HCO3− exchanger activity in immortalized renal proximal tubular epithelial cells from the SHR

Simão¹,

Gomes²,

José³

et al. 2010

Biochemical Pharmacology

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. Increased responsiveness to JNK1/2 mediates the enhanced HO-induced stimulation of Cl/HCO exchanger activity in immortalized renal proximal tubular epithelial cells from the SHR. Biochemical Pharmacology, Elsevier, 2010, 80 (6) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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NADPH Oxidases, Reactive Oxygen Species, and Hypertension

Cited by 634 publications

References 161 publications

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

Branched‐chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation

The effect of short-term canola oil ingestion on oxidative stress in the vasculature of stroke-prone spontaneously hypertensive rats

Increased responsiveness to JNK1/2 mediates the enhanced H2O2-induced stimulation of Cl−/HCO3− exchanger activity in immortalized renal proximal tubular epithelial cells from the SHR

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