Mechanism of thrombin-induced vasodilation in human coronary arterioles
Mechanism of thrombin-induced vasodilation in human coronary arterioles
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DOI：
10.1152/ajpheart.00465.2002
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发表时间：
2003-04-01
影响因子：
4.8
通讯作者：
Gutterman, DD
中科院分区：
文献类型：
--
作者：
Bosnjak, JJ;Terata, K;Gutterman, DD
凝血酶（Thromb）作为凝血级联反应的一部分被激活，通过内皮百日咳毒素（PTX）敏感性G蛋白受体扩张导管动脉并释放一氧化氮（NO）。血栓还作用于下游微血管。因此，我们研究了Thromb是否扩张人冠状动脉（HCA）。用内皮素-1收缩右心耳的HCA 30-50%。在使用抑制剂之前和之后，使用视频显微镜评估血栓扩张（10（-4）-1 U/ml）。对血栓扩张无快速耐受性（最大扩张率= 87.0%，ED_（50）= 1.49 × 10 ~（-2））。血栓扩张被水蛭素或剥脱所消除，但不受PTX的影响。N-ω-硝基-L-精氨酸甲酯（n = 7）、吲哚美辛（n = 9）、H-1[1，2，4]恶二唑并[4，3-a]喹喔啉-1-酮（n = 6）、四乙基氯化铵（n = 5）和伊比利亚毒素（n = 4）均未减少血栓的扩张。然而，KCl（最大扩张= 89 +/- 5 vs. 20 +/- 10%; P < 0.05; n = 7）、四丁基铵。氯化物（最大扩张= 79 +/- 7对21 +/- 4%; P < 0.05; n = 5）和卡律巴毒素（最大扩张= 89 +/- 4对10 +/- 2%; P < 0.05; n = 4）减弱了对血栓的扩张。与动物模型相反，血栓诱导的人小动脉扩张不依赖于G（i）蛋白激活和NO释放。然而，血栓扩张是内皮的。依赖于连续应用，并涉及K+通道的激活。我们推测内皮源性超极化因子有助于HCA中血栓诱导的扩张。
Thrombin (Thromb), activated as part of the clotting cascade, dilates conduit arteries through an endothelial pertussis toxin (PTX)-sensitive G-protein receptor and releases nitric oxide (NO). Thromb also acts on downstream microvessels. Therefore, we examined whether Thromb dilates human coronary arterioles (HCA). HCA from right atrial appendages were constricted by 30-50% with endothelin-1. Dilation to Thromb (10(-4)-1 U/ml) was assessed before and after inhibitors with videomicroscopy. There was no tachyphylaxis to Thromb dilation (maximum dilation = 87.0%, ED50 = 1.49 X 10(-2)). Dilation to Thromb was abolished with either hirudin or denudation but was not affected by PTX. Neither N-omega-nitro-L-arginine methyl ester (n = 7), indomethacin (n = 9), H-1[1,2,4] oxadiazolo- [4,3 -a] quinoxalin-1-one (n = 6), tetraethylammonium chloride (n = 5), nor iberiotoxin (n = 4) reduced dilation to Thromb. However, KCl (maximum dilation = 89 +/- 5 vs. 20 +/- 10%; P < 0.05; n = 7), tetrabutylammonium. chloride (maximum dilation = 79 +/- 7 vs. 21 +/- 4%; P < 0.05; n 5), and charybdotoxin (maximum dilation = 89 +/- 4 vs. 10 +/- 2%; P < 0.05; n = 4) attenuated dilation to Thromb. In contrast to animal models, Thromb-induced dilation in human arterioles is independent of G(i)-protein activation and NO release. However, Thromb dilation is endothelium. dependent, is maintained on consecutive applications, and involves activation of K+ channels. We speculate that an endothelium-derived hyperpolarizing factor contributes to Thromb-induced dilation in HCA.