Methylglyoxal Augments Angiotensin II–Induced Contraction in Rat Isolated Carotid Artery

Journal of Pharmacological Sciences

Masashi Mukohda¹  Yukio Hara¹  Muneyoshi Okada¹  Hideyuki Yamawaki¹ 

[1] Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan

关键词: glucose metabolite;    vascular endothelium;    angiotensin;    reactive oxygen species;    smooth muscle contractility;   

DOI  :  10.1254/jphs.10206FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(30)Cited-By(9)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 F2α–receptor blocker, or SQ29548 (1 μM), a thromboxane A2–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.

【 授权许可】

Unknown