Methylglyoxal enhances sodium nitroprusside-induced relaxation in rat aorta.
The concentration of methylglyoxal (MGO), a metabolite of glucose, increases in plasma of type II diabetic patients as well as in tissues of hypertensive rats. We have previously shown that MGO inhibited noradrenaline (NA)-induced smooth muscle contraction in rat aorta. However, the effect of MGO on relaxing responses in isolated blood vessel remains to be clarified. Thus, we examined if MGO affects acetylcholine (ACh)- or sodium nitroprusside (SNP)-induced vasodilation on NA (100 nM)-induced pre-contraction in rat thoracic aorta. Treatment of endothelium-intact aorta with MGO (420 microM, 30 min) did not change ACh (1 nM - 3 microM)-induced endothelium-dependent relaxation. In contrast, treatment of endothelium-denuded aorta with MGO shifted the concentration-response curve for SNP (0.1 - 300 nM) to the left. MGO increased reactive oxygen species (ROS) production in smooth muscle on analysis of protein carbonylation. Anti-oxidant agents such as tempol (10 microM), catalase (5000 U/mL), and nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methylester (100 microM) had no effect on MGO-induced enhancement of SNP-induced relaxation. However, iberiotoxin (100 nM), a large-conductance Ca(2+)-activated K(+) (BK(Ca))-channel inhibitor, significantly prevented the effect. The present study revealed that MGO enhanced SNP-induced relaxation in a ROS-independent manner via in part opening smooth muscle BK(Ca) channels.
Mukohda
Masashi
M
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan.
Yamawaki
Hideyuki
H
Okada
Muneyoshi
M
Hara
Yukio
Y
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D050050:Protein Carbonylation; D011765:Pyruvaldehyde / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D009599:Nitroprusside; D011765:Pyruvaldehyde; D000109:Acetylcholine