title: Methylglyoxal accumulation in arterial walls causes vascular contractile dysfunction in spontaneously hypertensive rats.
abstract: 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.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mukohda
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Okada
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hara
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamawaki
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011765:Pyruvaldehyde / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D017127:Glycation End Products, Advanced; D006146:Guanidines; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D009599:Nitroprusside; D011765:Pyruvaldehyde; D000109:Acetylcholine; C004479:pimagedine