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Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats.
MedLine Citation:
PMID:  22971844     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Methylglyoxal (MGO) is a metabolite of glucose and perhaps mediates diabetes-related macrovascular complications including hypertension. In the present study, we examined if MGO accumulation affects vascular reactivity of isolated mesenteric artery from spontaneously hypertensive rats (SHR). Five-week-old SHR were treated with an MGO scavenger, aminoguanidine (AG), for 5 weeks. AG partially normalized increased blood pressure in SHR. In mesenteric artery from SHR treated with AG, increased accumulation of MGO-derived advanced glycation end-products was reversed. In mesenteric artery from SHR, AG normalized impaired acetylcholine (ACh)-induced relaxation and increased angiotensin (Ang) II-induced contraction. Reactive oxygen species (ROS) production increased in SHR mesenteric artery, and acute treatment with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor augmented ACh-induced relaxation. Protein expression of NOX1 and Ang II type 2 receptor (AT2R) increased in SHR mesenteric artery, which was normalized by AG. Acute treatment with an AT2R blocker but not a NOX inhibitor normalized the increased Ang II-induced contraction in SHR mesenteric artery. The present results demonstrate that MGO accumulation in mesenteric artery may mediate development of hypertension in SHR at least in part via increased ROS-mediated impairment of endothelium-dependent relaxation and AT2R-mediated increased Ang II contraction.
Authors:
Masashi Mukohda; Muneyoshi Okada; Yukio Hara; Hideyuki Yamawaki
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-23
Journal Detail:
Title:  Journal of pharmacological sciences     Volume:  -     ISSN:  1347-8648     ISO Abbreviation:  J. Pharmacol. Sci.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-9-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101167001     Medline TA:  J Pharmacol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan.
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