2010 Volume 114 Issue 4 Pages 390-398
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.