Antithrombotic and thrombolytic efficacy of YM-254890, a Gq/11 inhibitor, in a rat model of arterial thrombosis
Antithrombotic and thrombolytic efficacy of YM-254890, a Gq/11 inhibitor, in a rat model of arterial thrombosis
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DOI：
10.1160/th03-02-0115
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发表时间：
2003-09-01
影响因子：
6.7
通讯作者：
Shikama, H
中科院分区：
文献类型：
--
作者：
Kawasaki, T;Taniguchi, M;Shikama, H
我们观察了G(Q/11)抑制剂YM-254890在电诱导的大鼠颈动脉血栓形成模型中的抗血栓和溶栓作用。YM-254890静脉注射后可剂量依赖性地抑制二磷酸腺苷诱导的体外血小板聚集。团注。在血栓形成研究中，YM-254890在静脉注射剂量为3和10ug/kg时，呈剂量依赖性地延长闭塞时间。静脉注射10µg/kg可降低血管闭塞率。在溶栓实验中，YM-254890按30 mg/kg静脉注射。用改良的组织型纤溶酶原激活剂溶栓后，缩短了再通时间，防止了再闭塞。YM-254890在10ug/kg或更高的剂量下，显著改善了溶栓后的颈动脉通畅状况。然而，在30毫克/公斤或更高的剂量下，YM-254890降低了全身血压。这些结果表明，YM-254890可能对G(Q)介导的疾病有效，YM-254890是研究G(Q/11)生物学作用的有用工具。
We examined the antithrombotic and thrombolytic effects of the G(q/11) inhibitor YM-254890 in an electrically-induced carotid artery thrombosis model in rats. YM-254890 dose-dependently inhibited ex vivo ADP-induced platelet aggregation after i.v. bolus injection. In the thrombosis study, YM-254890 dose-dependently prolonged time to occlusion at doses of 3 and 10 mug/kg i.v. and decreased occlusion rate at 10 mug/kg i.v. In the thrombolysis study, YM-254890 at 30 mug/kg i.v. shortened the time to reperfusion and prevented reocclusion after thrombolysis with a modified tissue-type plasminogen activator. YM-254890, at 10 mug/kg and more, significantly improved carotid patency status after thrombolysis. However, at 30 mug/kg and more,YM-254890 decreased systemic blood pressure. These results suggest that YM-254890 may be effective for treating G(q)-mediated diseases, and that YM-254890 is a useful tool for investigating the biological roles of G(q/11).