title: Methylglyoxal augments angiotensin II-induced contraction in rat isolated carotid artery.
abstract: Methylglyoxal (MGO), a metabolite of glucose, accumulates in vascular tissues of a hypertensive animal. In the present study, we examined the effect of MGO on angiotensin (Ang) II-induced contraction of rat carotid artery. Treatment of carotid artery with MGO (420 µM, 30 min) significantly augmented Ang II (0.1 to 30 nM)-induced concentration-dependent contraction. The effect was abolished by the removal of endothelium. BQ-123 (1, 5 µM), an endothelin A-receptor blocker, had no effect on the MGO-induced enhancement of Ang II-induced contraction. AL8810 (1 µM), a prostaglandin F(2α)-receptor blocker, or SQ29548 (1 µM), a thromboxane A(2)-receptor blocker, was also ineffective. However, tempol (10 µM), a superoxide scavenger, and catalase (5000 U/mL), which metabolizes hydrogen peroxide to water, significantly prevented the effect of MGO. Combined MGO and Ang II treatment increased reactive oxygen species (ROS) production. Apocynin (10 µM) or gp91ds-tat (3 µM), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, significantly prevented the effect of MGO. Gp91ds-tat or an Ang II type 1-receptor (AT1R) blocker, losartan (10 µM), prevented the MGO-mediated increased ROS production. The present study revealed that MGO augments Ang II-induced contraction by increasing AT1R-mediated NADPH oxidase-derived superoxide and hydrogen peroxide production in endothelium of rat carotid artery.
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: Hideyuki
authors.initials: H
authors.lastname: Yamawaki
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Okada
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hara
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019255:NADPH Oxidases / Q000502:physiology; D011765:Pyruvaldehyde / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D013481:Superoxides; D000804:Angiotensin II; D011765:Pyruvaldehyde; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases