Role of Superoxide in Angiotensin II–Induced but Not Catecholamine-Induced Hypertension

Laursen, Jørn Bech; Rajagopalan, Sanjay; Galis, Zorina S.; Tarpey, Margaret M.; Freeman, Bruce Α.; Harrison, David G.

doi:10.1161/01.cir.95.3.588

Cited by 755 publications

(586 citation statements)

References 33 publications

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“…The observation that hyperglycaemia is required to detect angiotensin II-induced expression of VEGF in cultured smooth muscle cells [16] could also be related to the formation of radicals, because of an altered cellular redox state induced by hyperglycaemia. These in vitro observations agree closely with earlier in vivo observations in rat aorta, namely that infusion of angiotensin II increases the production of superoxide anions by activation of NADPH oxidase, an effect that could be blocked completely by losartan [29,30]. From these data on smooth muscle cells a sequence of events is suggested that connects cellular activation by angiotensin II via NADPH oxidase activation, superoxide production and HIF1a activation to the transcriptional activation of the VEGF gene.…”

Section: Discussionsupporting

confidence: 90%

Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy

et al. 2002

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Section: Discussionsupporting

confidence: 90%

Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy

et al. 2002

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“…Prolonged infusion of Ang II activates NAD(P)H oxidase in blood vessels (1,2,10,12), where it increases expression of the p22 phox , Nox-1, and Nox-4 components in VSMC from conduit vessels (33-35) and p67 phox in vascular adventitial cells (36). Small resistance vessels express gp91 phox , which also is upregulated by Ang II (37), and p67 phox and xanthine oxidase, which are unaffected by HS intake (8).…”

Section: Discussionmentioning

confidence: 99%

“…However, there is also substantial oxidative stress in the tissues or blood vessels of rats with desoxycorticosterone acetate-salt hypertension in which the circulating renin-angiotensin-aldosterone system is suppressed profoundly (4,5) and in models of salt-sensitive hypertension (6,7) and in normal rats fed a high-salt diet (8). Oxidative stress in hypertension has been demonstrated by the increased production of markers, such on the lipid peroxidation products isoprostanes (9) and malonyldialdehyde (MDA), and by BP lowering effects of cell-permeable forms of SOD (10) or its mimetics (9). O 2 ·Ϫ is produced in activated phagocytes by the enzyme NADPH oxidase (2,11).…”

mentioning

confidence: 99%

Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase

Kitiyakara

Chabrashvili²,

Chen³

et al. 2003

Journal of the American Society of Nephrology

281

236

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Abstract. The hypothesis that a high salt (HS) intake increases oxidative stress was investigated and was related to renal cortical expression of NAD(P)H oxidase and superoxide dismutase (SOD). 8-Isoprostane PGF 2␣ and malonyldialdehyde were measured in groups (n ϭ 6 to 8) of conscious rats during low-salt, normal-salt, or HS diets. NADPH-and NADH-stimulated superoxide anion (O 2 ·Ϫ ) generation was assessed by chemiluminescence, and expression of NAD(P)H oxidase and SOD were assessed with real-time PCR. Excretion of 8-isoprostane and malonyldialdehyde increased incrementally twoto threefold with salt intake (P Ͻ 0.001), whereas prostaglandin E 2 was unchanged. Renal cortical NADH-and NADPHstimulable O 2 ·Ϫ generation increased (P Ͻ 0.05) 30 to 40% with salt intake. Compared with low-salt diet, HS significantly (P Ͻ 0.005) increased renal cortical mRNA expression of gp91 phox and p47 phox and decreased expression of intracellular CuZn (IC)-SOD and mitochondrial (Mn)-SOD. Despite suppression of the renin-angiotensin system, salt loading enhances oxidative stress. This is accompanied by increased renal cortical NADH and NADPH oxidase activity and increased expression of gp91 phox and p47 phox and decreased IC-and Mn-SOD. Thus, salt intake enhances generation of O 2 ·Ϫ accompanied by enhanced renal expression and activity of NAD(P)H oxidase with diminished renal expression of IC-and Mn-SOD.

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“…Accumulating evidence suggests that hypertension increases vascular production of reactive oxygen species, which can serve to oxidize BH 4 and lead to eNOS uncoupling. 9,10 Our previous experimental studies have shown that BH 4 is oxidized to dihydrobiopterin in the vasculature of the deoxycorticosterone acetate salt hypertensive mouse, and supplementation with oral BH 4 can reduce BP and improve oxidative stress in this model. 11 Several studies have assessed the effects of BH 4 on endothelial function.…”

Section: Introductionmentioning

confidence: 99%

Tetrahydrobiopterin: a novel antihypertensive therapy

et al. 2008

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Tetrahydrobiopterin (BH 4 ) is a cofactor for the nitric oxide (NO) synthase enzymes, such that its insufficiency results in uncoupling of the enzyme, leading to release of superoxide rather than NO in disease states, including hypertension. We hypothesized that oral BH 4 will reduce arterial blood pressure (BP) and improve endothelial function in hypertensive subjects. Oral BH 4 was given to subjects with poorly controlled hypertension (BP 4135/85 mm Hg) and weekly measurements of BP and endothelial function made. In Study 1, 5 or 10 mg kg À1 day À1 of BH 4 (n ¼ 8) was administered orally for 8 weeks, and in Study 2, 200 and 400 mg of BH 4 (n ¼ 16) was given in divided doses for 4 weeks. Study 1: significant reductions in systolic (P ¼ 0.005) and mean BP (P ¼ 0.01) were observed with both doses of BH 4 . Systolic BP was 15 ± 15 mm Hg (P ¼ 0.04) lower after 5 weeks and persisted for the 8-week study period. Study 2: subjects given 400 mg BH 4 had decreased systolic (P ¼ 0.03) and mean BP (P ¼ 0.04), with a peak decline of 16±19 mm Hg (P ¼ 0.04) at 3 weeks. BP returned to baseline 4 weeks after discontinuation. Significant improvement in endothelial function was observed in Study 1 subjects and those receiving 400 mg BH 4 . There was no significant change in subjects given the 200 mg dose. This pilot investigation indicates that oral BH 4 at a daily dose of 400 mg or higher has a significant and sustained antihypertensive effect in subjects with poorly controlled hypertension, an effect that is associated with improved endothelial NO bioavailability.

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Role of Superoxide in Angiotensin II–Induced but Not Catecholamine-Induced Hypertension

Abstract: Hypertension caused by chronically elevated angiotensin II is mediated in part by .O2-, likely via degradation of endothelium-derived NO. Increased vascular .O2- may contribute to vascular disease in high renin/angiotensin II states.

Cited by 755 publications

References 33 publications

Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy

Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy

Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase

Tetrahydrobiopterin: a novel antihypertensive therapy

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