Methylglyoxal inhibits smooth muscle contraction in isolated blood vessels.
Methylglyoxal (MGO) is a metabolite of glucose. In addition to evidence that increased plasma MGO level is associated with diabetic vascular complications, recent studies demonstrated that MGO accumulated in vascular tissues of hypertensive animals. We hypothesized that MGO could directly affect vascular reactivity. To test the hypothesis, we examined effects of MGO on contraction of isolated blood vessels. Treatment of endothelium-denuded rat aorta with MGO (420 microM, 30 min) shifted the concentration-response curve for noradrenaline (NA: 1 nM-1 microM) to the right. The inhibitory effect was concentration-dependent (MGO: 42-420 microM). Indomethacin (10 microM) and cimetidine (30 microM) could not prevent the inhibitory effect of MGO. However, a non-selective K(+)-channel inhibitor, tetramethylammonium (10 mM), prevented it. Glibenclamide (3 microM), an ATP-sensitive K(+)-channel inhibitor or apamin (1 microM), a small conductance Ca(2+)-activated K(+)-channel inhibitor was ineffective, but iberiotoxin (100 nM), a large conductance Ca(2+)-activated K+ (BK(Ca))-channel inhibitor significantly prevented the effect of MGO. MGO (420 microM, 30 min) also inhibited the NA (1 nM-1 microM)-induced contraction in mesenteric artery. The present results indicate that MGO has an inhibitory effect on contractility of isolated blood vessel, which is mediated via opening smooth muscle BK(Ca) channel.
Mukohda
Masashi
M
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan.
Yamawaki
Hideyuki
H
Nomura
Hidemi
H
Okada
Muneyoshi
M
Hara
Yukio
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011765:Pyruvaldehyde / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D026902:Potassium Channel Blockers; D011765:Pyruvaldehyde; D005905:Glyburide; D009638:Norepinephrine