Methylglyoxal Enhances Sodium Nitroprusside–Induced Relaxation in Rat Aorta

Journal of Pharmacological Sciences

Masashi Mukohda¹  Yukio Hara¹  Muneyoshi Okada¹  Hideyuki Yamawaki¹ 

[1] Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan

关键词: glucose metabolite;    vascular smooth muscle;    relaxation;    potassium channel;    reactive oxygen species;   

DOI  :  10.1254/jphs.09219FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(46)Cited-By(15)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 μM, 30 min) did not change ACh (1 nM – 3 μM)–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 μM), catalase (5000 U/mL), and nitric oxide synthase inhibitor, NG-nitro-L-arginine methylester (100 μM) had no effect on MGO-induced enhancement of SNP-induced relaxation. However, iberiotoxin (100 nM), a large-conductance Ca2+-activated K+ (BKCa)–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 BKCa channels.

【 授权许可】

Unknown