Role of hydrogen peroxide in ACh-induced dilation of human submucosal intestinal microvessels

Hatoum, Ossama A.; Binion, David G.; Miura, Hiroto; Telford, Gordon L.; Otterson, Mary F.; Gutterman, David D.

doi:10.1152/ajpheart.00663.2004

Cited by 45 publications

(51 citation statements)

References 55 publications

(78 reference statements)

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“…However, the ROS scavengers MnTBAP, a SOD mimetic, and PEG-CAT eliminated FID. This is consistent with previous studies where scavenging H 2 O 2 with catalase blocked flow and agonist-induced dilation in both human (17,35) and some animal (18) (40). MnTBAP, however, has both superoxide-and H 2 O 2 -scavenging effects (11), which might explain its net inhibitory action on FID in this study (see RESULTS).…”

Section: Discussionsupporting

confidence: 93%

“…1). In many cases, other endothelium-derived dilator substances compensate for the lack of NO release during flow (38) or agonist activation (17,38,54). This is consistent with the current observations since L-NAME plus Indo had no effect on FID in arterioles from patients with CAD.…”

Section: Discussionsupporting

confidence: 91%

“…Similar to previous studies showing increased ROS generation in patients with CAD (33,50), flow-induced generation of H 2 O 2 and superoxide fluorescence increased in adipose arterioles in patients with CAD more than in control patients without CAD. The effect of catalase on reducing H 2 O 2 production confirms specificity of the DCFH fluorescence (17,38). Taken together, these data emphasize the role of H 2 O 2 in mediating FID in adipose arterioles and suggest that the increased H 2 O 2 generation during CAD (33,38) is supported by the adipose circulation in patients with coronary disease.…”

Section: H97 Human Adipose Circulation and Mechanisms Of Fidsupporting

confidence: 65%

“…Figure 2 demonstrates that FID in vessels from patients without CAD was reduced in the presence of L-NAME (MD: 25.2 Ϯ 6%; n ϭ 11 vs. control MD: 75 Ϯ 5%) alone or in combination with Indo (MD 15.2 Ϯ 10%; n ϭ 6). These studies utilized concentrations of Indo and L-NAME previously shown to inhibit cyclooxygenase and NOS, respectively (17,25,54). FID is NOS dependent in adipose arterioles from patients without CAD since the effect of Indo and L-NAME on FID was not statistically different from L-NAME alone.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, FID in coronary arterioles from patients with CAD is maintained primarily by the ROS, hydrogen peroxide (H 2 O 2 ), and epoxyeicosatrienoic acid (33,38). Other studies implicate H 2 O 2 as an endotheliumderived hyperpolarizing factor (EDHF) in the mesenteric circulation of mice (36) and humans (17,35). It is not known whether ROS-dependent mechanisms of vasodilation also occur in adipose during CAD.…”

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confidence: 99%

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The mechanism of flow-induced dilation in human adipose arterioles involves hydrogen peroxide during CAD

Phillips

Hatoum

Gutterman

2007

American Journal of Physiology-Heart and Circulatory Physiology

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106

116

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Phillips SA, Hatoum OA, Gutterman DD. The mechanism of flowinduced dilation in human adipose arterioles involves hydrogen peroxide during CAD. Am J Physiol Heart Circ Physiol 292: H93-H100, 2007. First published October 13, 2006; doi:10.1152/ajpheart.00819.2006 is an important physiological stimulus that regulates tissue blood flow and is mediated by endotheliumderived factors that play a role in vascular integrity and the development of atherosclerosis. In coronary artery disease (CAD), conduit artery FID is impaired. The purpose of this study was to determine the mechanism of FID in human visceral adipose and examine whether the presence of conduit coronary atherosclerosis is associated with altered endothelial function in visceral fat. FID was determined in isolated visceral fat arterioles from patients with and without CAD. After constriction with endothelin-1, increases in flow produced an endothelium-dependent vasodilation that was sensitive to N -nitro-Larginine methyl ester (L-NAME) in visceral fat arterioles from patients without CAD. In contrast, L-NAME alone or in combination with indomethacin had no effect on FID in similarly located arterioles from patients with CAD. Flow increased dichlorofluorescein (DCF) and dihydroethidium fluorescence accumulation in arterioles from patients with CAD versus without, indicative of the production of oxidative metabolites and superoxide, respectively. Both the dilation and DCF fluorescence to flow were reduced in the presence of the H 2O2 scavenger polyethylene glycol-catalase. Exogenous H2O2 elicited similar relaxations of arterioles from patients in both groups. These data indicate that FID in visceral fat arterioles is nitric oxide dependent in the absence of known CAD. However, in the presence of CAD, H 2O2 replaces nitric oxide as the mediator of endotheliumdependent FID. This study provides evidence that adverse microvascular changes during CAD are evident in human visceral adipose, a tissue associated with CAD. coronary artery disease; blood flow; vasodilation; microcirculation FLOW-INDUCED DILATION (FID) is a physiologically important stimulus regulating vascular tone and homeostasis of the peripheral circulation. This important endothelial mechanism of vasodilation occurs in virtually every vascular bed and, in large arteries, may be critical for preventing atherosclerosis through release of the endothelium-derived antiproliferative compounds nitric oxide (NO) and prostacyclin (PGI 2 ) (21,25,39,51). Many of the studies implicating the role of NO (24) and PGI 2 (26) in FID have been performed in animal models in the absence of coronary artery disease (CAD). However, no studies have evaluated the mechanism of FID in isolated human microvessels from human visceral adipose with or without CAD. Human adipose has been proposed as a source for endocrine and paracrine modulation of vascular function during the establishment of atherosclerosis, and therefore vessels in this region could serve as sentinels for endothelial alterations produced by the proatheroscler...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: H97 Human Adipose Circulation and Mechanisms Of Fidsupporting

confidence: 65%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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The mechanism of flow-induced dilation in human adipose arterioles involves hydrogen peroxide during CAD

Phillips

Hatoum

Gutterman

2007

American Journal of Physiology-Heart and Circulatory Physiology

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106

116

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Hydrogen peroxide induces vasorelaxation by enhancing 4-aminopyridine-sensitive Kv currents through S-glutathionylation

Park

Noh

Sung

et al. 2014

Pflugers Arch - Eur J Physiol

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Hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor. Since opposing vasoactive effects have been reported for H2O2 depending on the vascular bed and experimental conditions, this study was performed to assess whether H2O2 acts as a vasodilator in the rat mesenteric artery and, if so, to determine the underlying mechanisms. H2O2 elicited concentration-dependent relaxation in mesenteric arteries precontracted with norepinephrine. The vasodilatory effect of H2O2 was reversed by treatment with dithiothreitol. H2O2-elicited vasodilation was significantly reduced by blocking 4-aminopyridine (4-AP)-sensitive Kv channels, but it was resistant to blockers of big-conductance Ca2+-activated K+ channels and inward rectifier K+ channels. A patch-clamp study in mesenteric arterial smooth muscle cells (MASMCs) showed that H2O2 increased Kv currents in a concentration-dependent manner. H2O2 speeded up Kv channel activation and shifted steady state activation to hyperpolarizing potentials. Similar channel activation was seen with oxidized glutathione (GSSG). The H2O2-mediated channel activation was prevented by glutathione reductase. Consistent with S-glutathionylation, streptavidin pull-down assays with biotinylated glutathione ethyl ester showed incorporation of glutathione (GSH) in the Kv channel proteins in the presence of H2O2. Interestingly, conditions of increased oxidative stress within MASMCs impaired the capacity of H2O2 to stimulate Kv channels. Not only was the H2O2 stimulatory effect much weaker, but the inhibitory effect of H2O2 was unmasked. These data suggest that H2O2 activates 4-AP-sensitive Kv channels, possibly through S-glutathionylation, which elicits smooth muscle relaxation in rat mesenteric arteries. Furthermore, our results support the idea that the basal redox status of MASMCs determines the response of Kv currents to H2O2.Electronic supplementary materialThe online version of this article (doi:10.1007/s00424-014-1513-3) contains supplementary material, which is available to authorized users.

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Endothelial nitric oxide synthase activation leads to dilatory H2O2 production in mouse cerebral arteries

Drouin

Thorin‐Trescases

Hamel

et al. 2007

Cardiovascular Research

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Role of hydrogen peroxide in ACh-induced dilation of human submucosal intestinal microvessels

Cited by 45 publications

References 55 publications

The mechanism of flow-induced dilation in human adipose arterioles involves hydrogen peroxide during CAD

The mechanism of flow-induced dilation in human adipose arterioles involves hydrogen peroxide during CAD

Hydrogen peroxide induces vasorelaxation by enhancing 4-aminopyridine-sensitive Kv currents through S-glutathionylation

Endothelial nitric oxide synthase activation leads to dilatory H2O2 production in mouse cerebral arteries

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