Methylglyoxal augments angiotensin II-induced contraction in rat isolated carotid artery

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. ©2010 the japanese pharmacological society.