Synthetic peroxisome proliferator-activated receptor-γ agonists restore impaired vasorelaxation via ATP-sensitive K+ channels by high glucose
Synthetic peroxisome proliferator-activated receptor-γ agonists restore impaired vasorelaxation via ATP-sensitive K+ channels by high glucose
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DOI：
10.1124/jpet.106.100958
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发表时间：
2006-07-01
影响因子：
3.5
通讯作者：
Hatano, Yoshio
中科院分区：
文献类型：
--
作者：
Kinoshita, Hiroyuki;Azma, Toshiharu;Hatano, Yoshio
本研究旨在检测在人动脉中，合成过氧化物酶体增殖激活受体(PPAR)- γ激动剂是否能通过被高浓度d -葡萄糖破坏的atp敏感K+通道恢复血管松弛和超极化，以及这种恢复是否可能由这些药物的抗氧化能力介导。记录无内皮人大网膜动脉的等长力和膜电位。在没有平滑肌细胞的情况下，使用含有黄嘌呤-黄嘌呤氧化酶的超氧化物生成系统来评估超氧化物的生产速率。格列本脲可消除左旋克马卡林引起的血管松弛和超极化。添加d -葡萄糖（20mm）而不添加l -葡萄糖（20mm）可减少这种血管松弛和超极化。合成ppar - γ激动剂（曲格列酮和罗格列酮）和/或超氧化物生成抑制剂（4,5-二羟基-1,3-苯二磺酸，铁），但不是ppar - γ激动剂（非诺贝特），在d -葡萄糖治疗的动脉左旋克马卡林反应中恢复血管松弛和超极化。曲格列酮和罗格列酮降低了超氧化物的生成速率，但不影响尿酸的生成，而非诺贝特没有。这些发现表明，合成ppar - γ激动剂可以恢复人血管平滑肌细胞中因高浓度葡萄糖而减少的atp敏感K+通道的功能，并且这些激动剂的作用可能部分由其抗氧化能力介导。
The present study was designed to examine whether in the human artery, synthetic peroxisome proliferator-activated receptor (PPAR)-gamma agonists restore vasorelaxation as well as hyperpolarization via ATP-sensitive K+ channels impaired by the high concentration of D-glucose and whether the restoration may be mediated by the antioxidant capacity of these agents. The isometric force and membrane potential of human omental arteries without endothelium were recorded. The production rate of superoxide was evaluated using a superoxide-generating system with xanthine-xanthine oxidase in the absence of smooth muscle cells. Glibenclamide abolished vasorelaxation and hyperpolarization in response to levcromakalim. Addition of D-glucose (20 mM) but not L-glucose (20 mM) reduced this vasorelaxation and hyperpolarization. Synthetic PPAR-gamma agonists (troglitazone and rosiglitazone) and/or an inhibitor of superoxide generation (4,5-dihydroxy-1,3-benzene-disulfonic acid, Tiron), but not a PPAR-gamma agonist (fenofibrate), restored vasorelaxation and hyperpolarization in response to levcromakalim in arteries treated with D-glucose. Troglitazone and rosiglitazone, but not fenofibrate, decreased the production rate of superoxide without affecting uric acid generation. These findings suggest that synthetic PPAR-gamma agonists recover the function of ATP-sensitive K+ channels reduced by the high concentration of glucose in human vascular smooth muscle cells and that the effect of these agonists may be mediated in part by their antioxidant capacity.