Methylglyoxal Enhances Sodium Nitroprusside-Induced Relaxation in Rat Aorta
Methylglyoxal Enhances Sodium Nitroprusside-Induced Relaxation in Rat Aorta
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DOI：
10.1254/jphs.09219fp
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发表时间：
2010-02-01
影响因子：
3.5
通讯作者：
Hara, Yukio
中科院分区：
文献类型：
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作者：
Mukohda, Masashi;Yamawaki, Hideyuki;Hara, Yukio
葡萄糖代谢产物甲基乙二醛（MGO）在2型糖尿病患者血浆中的浓度升高，在高血压大鼠组织中的浓度也升高。我们以前已经表明，MGO抑制去甲肾上腺素（NA）诱导的大鼠主动脉平滑肌收缩。然而，MGO对离体血管舒张反应的影响尚不清楚。因此，我们研究了MGO是否影响乙酰胆碱（ACh）或硝基（SNP）诱导的血管舒张对NA（100 nM）诱导的大鼠胸主动脉预收缩。用MGO（420 μ M，30 mm）处理内皮完整的主动脉，不改变ACh（1 nM-3 μ M）诱导的内皮依赖性舒张。与此相反，用MGO处理去内皮的主动脉使SNP（0.1 - 300 nM）的浓度-反应曲线左移。抗氧化剂如tempol（10 μ M）、过氧化氢酶（5000 U/mL）和一氧化氮合酶抑制剂N（G-）硝基-L-精氨酸甲酯（100 μ M）对MGO诱导的SNP诱导的舒张增强没有影响。然而，伊比利亚毒素（100 nM），一个大电导的Ca-2 i-激活的K+（BKCa）-通道抑制剂，显着阻止的效果。本研究表明，MGO通过部分开放平滑肌BKCa通道以ROS非依赖性方式增强SNP诱导的舒张。
The concentration of methylglyoxal (MGO), a metabolite of glucose, increases in plasma of type II diabetic patients as wella s 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 clairified. Thsu, we examined if MGO affects acetylcholine (ACh)- or sodium nitro prusside (SNP)-induced vasodilation on NA (100 nM)-induced pre-contraction in rat thoracic aorta. Treatment of endothelium-intact aorta with MGO(420 mu M, 30mm) did not change ACh(1nM-3 mu M)-induced endothelium-dependent relaxation. In contrasat, treatment of endothelium-denudeda aorta with MGO shifted the concetration-response curve for SNP(0.1 - 300nM) 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 mu M), catalase (5000 U/mL), and nitric oxide synthase inhibitor, N(G-)nitro-L-arginine methylester(100 mu M) has no effect on MGO-induced enhancement of SNP-induced relaxation. However, iberiotoxin (100 nM), a large-conductance Ca-2i - activated K+ (BKCa)-channel inhibitor, significantly prevented the effect. The present study revealed that MGO enhanced SNP-induced relaxatuib ub a ROS-independent manner via in part opening smooth muscle BKCa channels.