Vascular NADH/NADPH Oxidase Is Involved in Enhanced Superoxide Production in Spontaneously Hypertensive Rats

Zalba, Guillermo; Beaumont, Francisco J.; José, Gorka San; Fortuño, Ana; Fortuño, María Antonia; Etayo, Juan C.; Dı́ez, Javier

doi:10.1161/01.hyp.35.5.1055

Cited by 329 publications

(274 citation statements)

References 50 publications

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“…Alternatively, the increased NADPH oxidase activity may come from the upregulated expression of NADPH oxidase. In aorta of DOCA-salt hypertensive rats, p22 phox mRNA is increased, accompanied with an increased NADPH oxidase activity (49). In vivo ANG II treatment (7 days) in rats upregulates the expression of NADPH oxidase subunits and significantly increases NADPH oxidase activity (33).…”

Section: Discussionmentioning

confidence: 99%

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Dai

Chen²,

Kreulen³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Ϫ ⅐) production is elevated in sympathetic ganglion neurons and in the vasculature of hypertensive animals; however, it is not known what enzymatic pathway(s) are responsible for O 2 Ϫ ⅐ production. To determine the pathway(s) of O 2 Ϫ ⅐ production in sympathetic neurons, we examined the presence of mRNA of NADPH oxidase subunits in sympathetic ganglionic neurons and differentiated PC-12 cells. The mRNAs for NADPH oxidase subunits p47 phox , p22 phox , gp91 phox , and NOX1 were present in sympathetic neurons and PC-12 cells, whereas the NOX4 homologue was present in sympathetic neurons but not PC-12 cells. Freshly dissociated celiac ganglion neurons from normal rats and PC-12 cells produced O 2 Ϫ ⅐ when treated with the PKC activator PMA; O 2 Ϫ ⅐ production increased by 317% and 254%, respectively. The PMA-evoked increases were reduced by pretreatment with the NADPH oxidase inhibitor apocynin. These findings indicate that NADPH oxidase is the primary source of O 2 Ϫ ⅐ in sympathetic ganglion neurons. When celiac ganglia from hypertensive rats were incubated with apocynin, O 2 Ϫ ⅐ levels were reduced to the same levels as normotensive animals, indicating that NADPH oxidase activity accounted for the elevated O 2 Ϫ ⅐ levels in hypertensive animals. To test this latter finding, we compared NADPH oxidase activity in extracts of prevertebral sympathetic ganglia of DOCA-salt hypertensive rats and shamoperated rats. NADPH oxidase activities were 49.9% and 78.6% higher in sympathetic ganglia of DOCA rats compared with normotensive controls when using ␤-NADH and ␤-NADPH as substrates, respectively. Thus elevated O 2 Ϫ ⅐ levels in hypertension may be a result of the increased activity of NADPH oxidase in postganglionic sympathetic neurons. sympathetic ganglia; phorbol ester; reduced nicotinamide adenine dinucleotide phosphate oxidase; hypertension; deoxycorticosterone acetate VASCULAR ENDOTHELIAL CELLS, smooth muscle cells, and fibroblasts generate reactive oxygen species (ROS), such as O 2 Ϫ ⅐ and H 2 O 2 . ROS play critical roles in both normal and pathophysiological states of vascular cells, including the modulation of redox-sensitive signaling pathways and gene expression, or in the pathophysiology of hypertension and atherosclerosis (16,22,26,36). Several models of hypertension are associated with an increase in vascular O 2 Ϫ ⅐ (41, 42), and this increased O 2 Ϫ ⅐ may quench the endogenous vasodilator nitric oxide (NO) to cause a loss of NO bioactivity in the vessel wall and impair the endothelium-dependent vasorelaxation, resulting in hypertension (26). ROS-mediated endothelial dysfunction in ANG II-infused rats (24) and in DOCA-salt hypertensive rats (42) can be reversed by antioxidant enzyme, endothelial NO synthase (34), or superoxide dismutase (26). ROS can also induce the expression of cardiovascular-related genes, such as those for adhesion molecules and vasoactive substances. For example, the cytokine interleukin 1 activates VCAM-1 gene expression through a mechanism that is repressed ϳ90% by the antioxidant...

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Section: Discussionmentioning

confidence: 99%

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Dai

Chen²,

Kreulen³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Zalba et al 27 demonstrated increased production of superoxide anion in SHRs. Conversely, animal studies showed that the attenuation of cellular oxidative stress by overexpression of superoxide dismutase (SOD) or treatment with antioxidants attenuated these blood pressure elevations.…”

Section: Interaction Of Oxidative Stress and Inflammation In The Devementioning

confidence: 97%

Hypertension as an autoimmune and inflammatory disease

et al. 2016

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“…59,60,68 Ang II-induced NADPH oxidase activation is one of the major sources of ROS in atherosclerosis. 18,19,67,68 Zalba et al 68 showed that endothelial dysfunction is due to an excess of ROS rather than a decrease in NO production in the aorta of spontaneously hypertensive rats and is associated with both upregulation of p22 phox mRNA expression and increased activity of NADPH oxidase. Upregulation of p22 phox mRNA expression is a key component of Ang II-induced NADPH oxidase activation, and increased expression levels of other components also have an important role in this oxidase under pathological conditions.…”

Section: Oxidative Stressmentioning

confidence: 99%

Endothelial dysfunction and hypertension in aging

2012

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Hypertension is one of the common diseases in the elderly. The prevalence of hypertension markedly increases with advancing age. Both aging and hypertension have a critical role in cardiovascular and cerebrovascular complications. Although aging and hypertension, either independently or collectively, impair endothelial function, aging and hypertension may have similar cascades for the pathogenesis and development of endothelial dysfunction. Nitric oxide (NO) has an important role in regulation of vascular tone. Decrease in NO bioavailability by endothelial dysfunction would lead to elevation of blood pressure. An imbalance of reduced production of NO or increased production of reactive oxygen species, mainly superoxide, may promote endothelial dysfunction. One possible mechanism by which the prevalence of hypertension is increased in relation to aging may be advancing endothelial dysfunction associated with aging through an increase in oxidative stress. In addition, endothelial cell senescence is also involved in aging-related endothelial dysfunction. In this review, we focus on recent findings and interactions between endothelial function, oxidative stress and hypertension in aging.

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Vascular NADH/NADPH Oxidase Is Involved in Enhanced Superoxide Production in Spontaneously Hypertensive Rats

Cited by 329 publications

References 50 publications

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Hypertension as an autoimmune and inflammatory disease

Endothelial dysfunction and hypertension in aging

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