Long-Term Methylglyoxal Treatment Causes Endothelial Dysfunction of Rat Isolated Mesenteric Artery
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- MUKOHDA Masashi
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, Japan
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- MORITA Tomoka
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, Japan
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- OKADA Muneyoshi
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, Japan
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- HARA Yukio
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, Japan
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- YAMAWAKI Hideyuki
- Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, Japan
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Abstract
Methylglyoxal (MGO) is a metabolite of glucose and likely related to pathogenesis of diabetes-related vascular complications including hypertension. In this study, long-term effects of MGO on endothelial function were examined. Rat isolated mesenteric artery was treated for 3 days with MGO using an organ culture method. The contractility, morphology and protein expression of organ-cultured artery were examined. MGO (42 μM, 3 days) impaired acetylcholine (ACh: 1 nM–300 μM)-induced endothelium-dependent relaxation, while it had no effect on sodium nitroprusside (0.1 nM–10 μM)-induced endothelium-independent relaxation. MGO decreased ACh (3 μM)-induced nitric oxide (NO) production as measured by a fluorescence NO indicator, diaminofluorescein-2. Consistently, MGO inhibited ACh (3 μM)-induced phosphorylation of vasodilator stimulated phosphoprotein (an indicator of cyclic GMP production). MGO induced apoptosis in endothelium as detected by TdT-mediated dUTP-biotin nick-end labeling staining. MGO induced accumulation of superoxide in endothelium as detected by dihydroethidium staining. MGO decreased protein expression of endothelial NO synthase (eNOS). Gp91ds-tat (0.1 μM), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), prevented the impairment of endothelium-dependent relaxation and the decrease in eNOS protein caused by MGO. The present results demonstrated that long-term MGO treatment impairs endothelium-dependent relaxation through NOX-derived increased superoxide-mediated endothelial apoptosis.
Journal
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- Journal of Veterinary Medical Science
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Journal of Veterinary Medical Science 75 (2), 151-157, 2013
JAPANESE SOCIETY OF VETERINARY SCIENCE
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Details 詳細情報について
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- CRID
- 1390282681407168384
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- NII Article ID
- 130001879669
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- NII Book ID
- AA10796138
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- COI
- 1:STN:280:DC%2BC3s%2FgslymtA%3D%3D
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- ISSN
- 13477439
- 09167250
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- NDL BIB ID
- 024302761
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- PubMed
- 23018793
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed