Role of Oxidative Stress in Remodeling of the Myocardial Microcirculation in Hypertension

Zhu, Xiang Yang; Daghini, Elena; Chade, Alejandro; Rodriguez-Porcel, Martin; Napoli, Claudio; Lerman, Amir; Lerman, Lilach O.

doi:10.1161/01.atv.0000227469.40826.01

Cited by 40 publications

(55 citation statements)

References 42 publications

(52 reference statements)

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“…[76][77][78]93 In hypertensive animals chronic treatment with BH 4 has been shown to improve endothelium-dependent dilation though this treatment both increased NO production and reduced superoxide production. 74,94 These results suggest that at least part of the increased production of ROS and altered vasodilation may be explained by increased uncoupled eNOS-mediated production of superoxide, and subsequent reduced NO bioavailability. The reduction in BH 4 and/or increase in arginase 71 may propagate the uncoupling of eNOS and enhance superoxide production under these conditions.…”

Section: Enosmentioning

confidence: 86%

“…47 Thus it is not surprising that in hypertension the increased production of reactive oxygen species (ROS) is associated with an increased production of peroxynitrite in the heart and coronary blood vessels. 47,48,[73][74][75] The production of peroxynitrite itself has an impact on several pathways of vasodilation including reduced prostaglandin synthesis and inhibition of K + channels. 8,76 Additionally peroxynitrite impairs NO production through oxidation of BH 4 , a NOS co-factor 8,[76][77][78] and also impairs the sGC-mediated response to NO.…”

Section: Nitric Oxide-mediated Vasomotor Function Of Isolated Coronarmentioning

confidence: 99%

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Nitric oxide and coronary vascular endothelium adaptations in hypertension

Levy

Chung²,

Kroetsch

et al. 2009

VHRM

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This review highlights a number of nitric oxide (NO)-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS) to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca 2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been studied extensively to establish mechanisms for sex differences in NO-dependent function. Genomic and nongenomic effects of estrogen on eNOS and direct and indirect antioxidant activities of estrogen are discussed as potential mechanisms of interest in coronary circulation that could have implications for sex-and estrogen status-dependent therapy for hypertension and coronary dysfunction. The current review identifies some important basic knowledge gaps and speculates on the potential clinical relevance of hypertension adaptations in factors regulating coronary NO function.

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Section: Enosmentioning

confidence: 86%

Section: Nitric Oxide-mediated Vasomotor Function Of Isolated Coronarmentioning

confidence: 99%

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Levy

Chung²,

Kroetsch

et al. 2009

VHRM

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“…Our group has previously shown that chronic administration of experimental doses of vitamins E and C improves renal (5,44) and myocardial (32, 33) vascular function and decreases neovascularization (5,54,55) in hypercholesterolemia (5,55) and hypertension (54). These disease conditions are characterized by decreased systemic basal levels of antioxidant vitamins (due to increased consumption) and increased oxidative stress, and therefore antioxidant administration effectively elevates vitamin concentrations to levels only slightly higher than normal.…”

Section: Discussionmentioning

confidence: 99%

“…Twelve female domestic crossbred pigs (50 -60 kg) were randomized to receive a normal diet without (n ϭ 6) or with antioxidant vitamin supplementation (1 g/day vitamin C, 100 IU ⅐ kg Ϫ1 ⅐ day Ϫ1 vitamin E; vitamin supplemented, n ϭ 6) for 12 wk. Our group has previously shown that during increased oxidative stress associated with hypercholesterolemia or hypertension, this regimen is effective in restoring redox balance, decreasing neovascularization, and improving renal and myocardial vascular function (5,44,54,55).…”

Section: In Vivo Studymentioning

confidence: 99%

“…Kidneys were perfused ex vivo through a cannulated segmental renal artery with 0.9% saline (containing 10 U/ml heparin) for 10 -15 min, followed by an infusion of intravascular microfil silicone rubber (MV-122; Flow Tech, Carver, MA) infused at physiological pressure and a flow rate of 0.9 ml/min (2,5,9,54). After complete polymerization, sections of microfil-filled renal cortex were prepared and scanned at 0.5°angular increments, using a micro-CT scanner.…”

Section: In Vivo Studymentioning

confidence: 99%

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Antioxidant vitamins induce angiogenesis in the normal pig kidney

Daghini

Zhu

Versari

et al. 2007

American Journal of Physiology-Renal Physiology

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The effects of chronic supplementation with antioxidant vitamins on angiogenesis are controversial. The aim of the present study was to evaluate in kidneys of normal pigs the effect of chronic supplementation with vitamins E and C, at doses that are effective in reducing oxidative stress and attenuating angiogenesis under pathological conditions. Domestic pigs were randomized to receive a 12-wk normal diet without ( n = 6) or with antioxidant vitamins supplementation (1g/day vitamin C, 100 IU·kg−1·day−1 vitamin E; n = 6). Electron beam computed tomography (CT) was used to evaluate renal cortical vascular function in vivo, and micro-CT was to assess the spatial density and average diameter of cortical microvessels (diameter <500 μm) ex vivo. Oxidative stress and expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α were evaluated in renal tissue. The effects of increasing concentrations of the same vitamins on redox status and angiogenesis were also evaluated in human umbilical vascular endothelial cells (HUVEC). Compared with normal pigs, the density of cortical transmural microvessels was significantly greater in vitamin-supplemented pigs (149.0 ± 11.7 vs. 333.8 ± 48.1 vessel/cm2, P < 0.05), whereas the cortical perfusion response to ACh was impaired. This was accompanied by a significant increase in tissue oxidative stress and levels of VEGF and HIF-1α. A low dose of antioxidant decreased, whereas a high dose increased, HUVEC oxidative stress and angiogenesis, which was partly mediated by hydrogen peroxide. Antioxidant vitamin supplementation can increase tissue oxidative redox and microvascular proliferation in the normal kidney, probably due to a biphasic effect that depends on basal redox balance.

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Redox Regulation of the Microcirculation

Kadlec

Gutterman

2019

Comprehensive Physiology

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Role of Oxidative Stress in Remodeling of the Myocardial Microcirculation in Hypertension

Cited by 40 publications

References 42 publications

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Nitric oxide and coronary vascular endothelium adaptations in hypertension

Antioxidant vitamins induce angiogenesis in the normal pig kidney

Redox Regulation of the Microcirculation

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