Inhibition of acetylcholine-induced EDHF response by elevated glucose in rat mesenteric artery

Ozkan, Melike Hacer; Shanmugasundaram, Uma

doi:10.1016/j.lfs.2005.02.036

Cited by 24 publications

(24 citation statements)

References 44 publications

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Section: Discussionmentioning

confidence: 99%

“…4 Taken in conjunction with the reduced level of TNF-α, IL-1β, and IL-6 observed in the adipose tissue of DWM mice, the prevention of the impairment of EDHmediated relaxations observed in their arteries illustrates that An elevated glucose level inhibits acetylcholine-induced, EDH-mediated responses in the rat mesenteric artery because of the increased production of ROS. 23 The administration of the antioxidant apocynin prevented the reduction in EDHmediated relaxation, suggesting that the impaired response in arteries with functional TLR4 signaling also results from an increased ROS production.…”

Section: Discussionmentioning

confidence: 99%

“…An elevated glucose level inhibits acetylcholine-induced, EDH-mediated responses in the rat mesenteric artery because of the increased production of ROS. 23 The administration of the antioxidant apocynin prevented the reduction in EDHmediated relaxation, suggesting that the impaired response in arteries with functional TLR4 signaling also results from an increased ROS production.Third, the aberrant production of vasoactive factors causing endothelial dysfunction includes the increased release of EDCFs from endothelial cells. 24 In the mouse, EDCF-mediated responses are most pronounced in the carotid artery, 25 and therefore this preparation was selected to examine endothelium-dependent contractions.…”

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confidence: 99%

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Toll-Like Receptor 4 Mutation Protects Obese Mice Against Endothelial Dysfunction by Decreasing NADPH Oxidase Isoforms 1 and 4

Liang

Liu

Wang

et al. 2013

ATVB

104

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O besity and diabetes mellitus are associated with augmented circulating levels of free fatty acids, low-grade chronic inflammation, 1 and endothelial dysfunction attributable to impaired release of endothelium-derived relaxing and augmented production of endothelium-derived contracting (EDCF) factors.2 Thus, the bioavailability of NO is reduced by obesity and diabetes mellitus, 3 and relaxations attributable to endothelium-derived hyperpolarization (EDH) are impaired at the early stage of diabetes mellitus. 4 Finally, increased release of endothelium-derived vasoconstrictor prostanoids and reactive oxygen species (ROS) also contributes to endothelial dysfunction in obesity and diabetes mellitus. 5 Proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin 6 [IL-6], resistin, and lipocalin-2) link obesity to metabolic and vascular dysfunction.1 Bacterial endotoxin lipopolysaccharide (LPS) and saturated fatty acids share as pattern recognition target toll-like receptors 4 (TLR4), which activate inflammatory pathways, induce cytokine expression in the endothelium, 6,7 and augment the expression of NADPH oxidase in macrophages. 8 The absence of TLR4 protects mice against obesity-induced insulin resistance. 7NADPH oxidase is a major source of endothelial ROS. 9,10 ROS decrease the bioavailability of NO 11 and facilitate the production of EDCF. 12It is unknown whether or not TLR4 signaling contributes to the impaired NO-and EDHF-mediated relaxations and the amplified EDCF-mediated contractions seen in obesity and diabetes mellitus. Therefore, the present experiments tested the hypothesis that TLR4 signaling mediates, at least in part, the deleterious effects of diet-induced and genetic obesity leading to endothelial dysfunction. Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results General CharacteristicsThere were no significant differences in food intake between wild-type (WT) and TLR4 −/− mice ( Figure Objective-To analyze the role of toll-like receptor 4 in modulating metabolism and endothelial function. Approach and Results-Type 2 diabetic mice with mutated toll-like receptor 4 (DWM) were protected from hyperglycemia and hypertension, despite an increased body weight. Isometric tension was measured in arterial rings with endothelium.Relaxations to acetylcholine were blunted in aortae and mesenteric arteries of Lepr db/db mice, but not in DWM mice; the endothelial NO synthase dimer/monomer ratio and endothelial NO synthase phosphorylation levels were higher in DWM preparations. These differences were abolished by apocynin. Contractions to acetylcholine (in the presence of L-NAME) were larger in carotid arteries from Lepr db/db mice than from DWM mice and were inhibited by indomethacin and SC560, demonstrating involvement of cyclooxygenase-1. The release of 6-ketoprostaglandin F 1α was lower in DWM mice arteries, implying lower cyclooxygenase-1 activity. Apocynin, manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin, catalase, and diethyldithiocarbamat...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Toll-Like Receptor 4 Mutation Protects Obese Mice Against Endothelial Dysfunction by Decreasing NADPH Oxidase Isoforms 1 and 4

Liang

Liu

Wang

et al. 2013

ATVB

104

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“…AP-induced relaxation had no ability to overwhelm depolarizedcontraction (0.3-100 mg/ml of AP). It is well known that vascular tone is closely associated with membrane potential and that depolarization by high extracellular K þ ions easily closes K þ channels without muscarinic acetylcholine-receptor/cAMP stimulation, 18) followed by the opening of voltage-gated Ca 2þ channels or vasocontraction in the smooth muscle. 19) In that study, less relaxation of AP in 70 mM KCl-contractive rat aorta rings suggested that AP plays a role in the induction of membrane hyperpolarization by activating K þ channels.…”

Section: Discussionmentioning

confidence: 99%

Apple Procyanidins Induced Vascular Relaxation in Isolated Rat Aorta through NO/cGMP Pathway in Combination with Hyperpolarization by Multiple K⁺Channel Activations

Matsui

Korematsu

Byun

et al. 2009

Bioscience, Biotechnology, and Biochemistry

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“…The latter component has been shown to be increased in obese Zucker rats and may mask a decrease in ACh-mediated NO synthesis (1). Second, different levels of blood glucose may determine ACh responses in blood vessels of obese Zucker rats (28,34), as impairment of AChmediated vasodilatation has been demonstrated in diabetic Zucker rats (14) but not in normoglycemic Zucker rats (1,21).…”

Section: Discussionmentioning

confidence: 99%

Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats

Eringa¹,

Stehouwer²,

Roos³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Eringa EC, Stehouwer CD, Roos MH, Westerhof N, Sipkema P. Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats. Am J Physiol Endocrinol Metab 293: E1134-E1139, 2007. First published July 10, 2007; doi:10.1152/ajpendo.00516.2006.-Obesity is related to insulin resistance and hypertension, but the underlying mechanisms are unclear. Insulin exerts both vasodilator and vasoconstrictor effects on muscle resistance arteries, which may be differentially impaired in obesity. Objectives: To investigate whether vasodilator and vasoconstrictor effects of insulin are impaired in muscle resistance arteries of obese rats and the roles of Akt and endothelial NO synthase (eNOS). Methods/Results: Effects of insulin were studied in resistance arteries isolated from cremaster muscles of lean and obese Zucker rats. In arteries of lean rats, insulin increased activity of both NO and endothelin (ET-1), resulting in a neutral effect under basal conditions. In arteries of obese rats, insulin induced endothelin-mediated vasoconstriction (Ϫ15 Ϯ 5% at 1 nM, P Ͻ 0.05 vs. lean). Insulin induced vasodilatation during endothelin receptor blockade in arteries of lean rats (20 Ϯ 5% at 1 nM) but not in those of obese rats. Inhibition of NO synthesis increased vascular tone (by 12 Ϯ 2%) and shifted insulinmediated vasoreactivity to vasoconstriction (Ϫ25 Ϯ 1% at 1 nM) in lean rats but had no effect in arteries of obese rats, indicating reduced NO activity. Protein analysis of resistance arteries revealed that insulin-mediated activation of Akt was preserved in obese rats, whereas expression of eNOS was markedly decreased. Conclusions: Vasodilator but not vasoconstrictor effects of insulin are impaired in muscle resistance arteries of obese rats, and this selective impairment is associated with decreased protein levels of eNOS. These findings provide a new mechanism linking obesity to insulin resistance and hypertension. microcirculation; obesity; hypertension; nitric oxide OBESITY IS ASSOCIATED WITH impairment of insulin-mediated insulin resistance, i.e., glucose disposal (19) and hypertension (29), but the mechanisms behind these relationships have not been elucidated.We and others have hypothesized that impaired endotheliumdependent vasodilatation in resistance arteries plays an important role in both insulin resistance and hypertension (32). Impaired endothelium-dependent vasodilatation in these arteries increases vascular resistance, which, in muscle, may contribute to decreased insulin-mediated glucose disposal (7).A specific type of endothelium-dependent vasodilatation that may be relevant in this regard is insulin-mediated vasodilatation. Both vasodilator and vasoconstrictor effects of insulin have been described, the normal response to insulin being vasodilator or neutral (8, 36). We and others have previously shown that, in muscle resistance arteries, NO-dependent vasodilator effects of insulin are antagonized by endothelin-mediated vasoconstrictor effects. It was previously show...

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Inhibition of acetylcholine-induced EDHF response by elevated glucose in rat mesenteric artery

Cited by 24 publications

References 44 publications

Toll-Like Receptor 4 Mutation Protects Obese Mice Against Endothelial Dysfunction by Decreasing NADPH Oxidase Isoforms 1 and 4

Toll-Like Receptor 4 Mutation Protects Obese Mice Against Endothelial Dysfunction by Decreasing NADPH Oxidase Isoforms 1 and 4

Apple Procyanidins Induced Vascular Relaxation in Isolated Rat Aorta through NO/cGMP Pathway in Combination with Hyperpolarization by Multiple K⁺Channel Activations

Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats

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Inhibition of acetylcholine-induced EDHF response by elevated glucose in rat mesenteric artery

Cited by 24 publications

References 44 publications

Toll-Like Receptor 4 Mutation Protects Obese Mice Against Endothelial Dysfunction by Decreasing NADPH Oxidase Isoforms 1 and 4

Toll-Like Receptor 4 Mutation Protects Obese Mice Against Endothelial Dysfunction by Decreasing NADPH Oxidase Isoforms 1 and 4

Apple Procyanidins Induced Vascular Relaxation in Isolated Rat Aorta through NO/cGMP Pathway in Combination with Hyperpolarization by Multiple K+Channel Activations

Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats

Contact Info

Product

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Apple Procyanidins Induced Vascular Relaxation in Isolated Rat Aorta through NO/cGMP Pathway in Combination with Hyperpolarization by Multiple K⁺Channel Activations