Methylglyoxal accumulation in arterial walls causes vascular contractile dysfunction in spontaneously hypertensive rats

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. © the japanese pharmacological society.