title: Long-term methylglyoxal treatment impairs smooth muscle contractility in organ-cultured rat mesenteric artery.
abstract: Methylglyoxal (MGO), a metabolite of glucose accumulates in vascular tissues of hypertensive rats. We recently showed that short-term (30min) treatment with MGO inhibits noradrenaline (NA)-induced smooth muscle contraction in rat aorta and mesenteric artery. In the present study, long-term effect of MGO was examined using organ culture method. The contractility, morphology, and protein expression of rat mesenteric artery after organ culture with MGO for 3 days were examined. MGO (4 and 42μM) inhibited NA (0.1nM to 3μM) or KCl (72.7mM)-induced contraction. The inhibitory effect was higher in endothelium-denuded than endothelium-intact artery. An anti-oxidant drug, N-acetyl-l-cysteine (NAC; 1mM) or an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), gp91ds-tat (0.1μM) prevented the inhibitory effect of MGO. MGO increased superoxide production as detected by lucigenin assay. In the medial layer of the arteries cultured with MGO, apoptotic morphological change was observed, and NAC or gp91ds-tat prevented it. MGO significantly increased expression of a homolog of gp91(phox), NOX1 but not gp91(phox) as determined by Western blotting. An NF-κB inhibitor, pyrrolidine dithiocarbamate prevented the MGO-induced NOX1 expression. MGO had no effect on protein expression of p22(phox), p67(phox), p47(phox), as well as superoxide dismutase (SOD)-1, SOD-2 and SOD-3. Present results indicate that long-term MGO treatment has an inhibitory effect on contractility of isolated blood vessel, which is likely mediated via increased NOX1-derived superoxide production and subsequent apoptosis.
authors: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan.
authors: Masashi
authors: M
authors: Mukohda
authors: Tomoka
authors: T
authors: Morita
authors: Muneyoshi
authors: M
authors: Okada
authors: Yukio
authors: Y
authors: Hara
authors: Hideyuki
authors: H
authors: Yamawaki
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000074624:NADPH Oxidase 1; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009924:Organ Culture Techniques; D011765:Pyruvaldehyde / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D014662:Vasoconstrictor Agents; D013481:Superoxides; D011765:Pyruvaldehyde; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614712:NOX1 protein, rat