Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone.

Rajagopalan, Sanjay; Kurz, Sabine; Münzel, Thomas; Tarpey, Margaret M.; Freeman, Bruce Α.; Griendling, Kathy K.; Harrison, David G.

doi:10.1172/jci118623

Cited by 2,258 publications

(1,772 citation statements)

References 35 publications

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“…28 In addition, both treatments prevent increased NO inactivation due to oxygen radicals by reducing Ang II type 1-receptor-dependent activation of the oxidant enzyme NADPH oxidase and enhancing EC-SOD activity. 29 Furthermore, an Ang II infusion reportedly resulted in increased superoxide anion production and NADPH-dependent oxidase activity, 30 leading to endothelial dysfunction in animal experiments, 31 though endothelial responses were restored by treatment with superoxide dismutase or ARB. 31 Recently, an improvement of endothelial dysfunction in hypertension has been reported to be associated with ACE2, a newly recognized homolog of ACE.…”

Section: Discussionmentioning

confidence: 99%

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

et al. 2011

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Endothelial dysfunction in essential hypertension is an independent predictor for future cardiovascular events. Although inhibition of the renin-angiotensin system (RAS) reportedly improves endothelial function through its effects on oxidative stress and inflammation, questions remain regarding the factors that are pivotal for improvement of endothelial function by RAS inhibition. We therefore performed a prospective, randomized crossover trial in which an angiotensin II type 1 receptor antagonist, olmesartan and calcium channel blocker, amlodipine, were compared in 31 essential hypertensive patients. Results showed that, although both treatments achieved comparable lowering of blood pressure (BP), olmesartan, but not amlodipine, significantly improved endothelial function as evaluated by flow-mediated vasodilation (FMD) in the brachial artery. Although no significant changes in diabetic and lipid parameters were observed with either drug, olmesartan slightly decreased estimated glomerular filtration rate, which, surprisingly, translated into decreased microalbuminuria. In a similar vein, olmesartan reduced serum C-reactive protein and increased urine antioxidant levels compared with baseline, and reduced urine 8-epi-prostaglandin F2a levels compared with both baseline and amlodipine. Finally, although overall changes in plasma extracellular superoxide dismutase (EC-SOD) levels were not modulated by either treatment, for olmesartan there was a positive correlation between changes in FMD and those in EC-SOD levels. In conclusion, olmesartan improved endothelial function in hypertensive patients independent of its BP-lowering effect, which was due, at least in part, to its antioxidative property. Therefore, olmesartan might provide a greater long-term benefit for hypertensive patients with impaired endothelial function than amlodipine.

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Section: Discussionmentioning

confidence: 99%

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

et al. 2011

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“…60 NADPH oxidase, which is a major source of production of ROS in vessel walls, is activated in hypertensive rats. 61,62 It has also been shown that ascorbic acid restores impaired endothelium-dependent vasodilation in patients with essential hypertension. 63 Therefore, enhanced production of ROS and an attenuated antioxidant system may contribute to endothelial dysfunction in patients with hypertension.…”

Section: Endothelial Dysfunction and Hypertensionmentioning

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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“…These increases in superoxide appear to be produced in part by activation of NAD(P)H oxidase. NAD(P)H oxidases are a major enzymatic source of superoxide in the systemic vasculature, and activity of NAD(P)H oxidase is increased in several pathophysiological states, including hypertension (Didion et al, 2002;Griendling et al, 2000;Rajagopalan et al, 1996a). NAD(P)H oxidase is also expressed and activated in cerebral blood vessels during chronic hypertension (Didion and Faraci, 2003;Girouard et al, 2007;Kazama et al, 2004;Paravicini et al, 2004).…”

Section: Superoxide and Hypertensionmentioning

confidence: 99%

Oxidative Stress through Activation of NAD(P)H Oxidase in Hypertensive Mice with Spontaneous Intracranial Hemorrhage

Wakisaka

Miller

Chu

et al. 2008

J Cereb Blood Flow Metab

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We have developed an experimental model of spontaneous intracranial hemorrhage (ICH) in transgenic mice expressing human renin and human angiotensinogen (R + /A + ) treated with highsalt diet and N x -nitro-L-arginine methyl ester (L-NAME). We investigated whether oxidative stress is associated with spontaneous ICH in R + /A + mice. R + /A + mice on high-salt diet and L-NAME presented neurologic signs 57±13 (mean±s.e.m.) days after the start of treatment. Intracranial hemorrhage was shown with histologic examination. Levels of superoxide in brain homogenate were significantly increased in R + /A + mice with ICH (118±10 RLU per sec per mg; RLU, relative light unit) compared with age-matched control mice (19 ± 1) and R + /A + mice without ICH (53 ± 3). NAD(P)H oxidase activity was significantly higher in R + /A + mice with ICH (34,933±2,420 RLU per sec per mg) than in control mice (4,984 ± 248) and R + /A + mice without ICH (15,069 ± 917). These results suggest that increased levels of superoxide are due, at least in part, to increased NAD(P)H oxidase activity. Increased NAD(P)H oxidase activity preceded signs of ICH, and increased further when R + /A + mice developed ICH. These findings suggest that oxidative stress may contribute to spontaneous ICH in chronic hypertension.

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Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone.

Abstract: We tested the hypothesis that angiotensin II-induced hypertension is associated with an increase in vascular и

Cited by 2,258 publications

References 35 publications

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

Endothelial dysfunction and hypertension in aging

Oxidative Stress through Activation of NAD(P)H Oxidase in Hypertensive Mice with Spontaneous Intracranial Hemorrhage

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