molecular mechanisms of vascular thrombosis

血管血栓形成的分子机制

基本信息

批准号：
07557058
负责人：
TAKESHITA Akira
金额：
$ 8.58万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

We have recently shown that chronic inhibition of nitric oxide (NO) synthesis by Nomega-nitro-L-arginine methyl ester (L-NAME) activates local angiotensin-converting enzyme (ACE) activity as well as induces vascular fibrosis and inflammatory changes in rats. Angiotensin II is known to activate coagulation cascade and inhibit fibrinolytic activity in the vessel wall.In the present study, we hypothesized that cyclic flow variations (CFV) , resulting from recurrent arterial thrombosis and its dislodgement, is induced in stenosed carotid arteries in a rat model of chronic inhibition of NO synthesis. Four groups of rats were studies : control group, L group received L-NAME,L+Hyd group received L-NAME and hydralazine, and L+A group received L-NAME and ACE inhibitor imidapril for 4 weeks. After anesthesia, stenosis was induced by constricting an exposed carotid artery, and CFV was determined using a ultrasonic flow prove. CFV provocation rate was 0% in the control group, 94% in the L group, 80% in the L+Hyd group, and 0% in the L+ACE inhibitor group. The carotid artery ACE activity was increased in the L and L+Hyd groups, and was suppressed in the L=ACE inhibitor group. In separate studies, treatment with thrombin antagonist argatroban, but not with vehicle or aspirin, nearly abolished CFV.There was no significant difference among groups in blood platelet count, platelet aggregation in response to collagen and indices of coagulation cascade (PT and APTT) .In conclusion, these findings suggest that CFV could be provoked by producing stenosis possibly via local thrombin generation in this animal model and that local ACE is likely to contribute to such changes.

我们最近表明，Nomega-Nitro-L-精氨酸甲酯（L-NAME）慢性抑制一氧化氧化物（NO）合成可激活局部血管紧张素转化酶（ACE）活性，并诱导大鼠的血管纤维化和炎症变化。 Angiotensin II is known to activate coagulation cascade and inhibit fibrinolytic activity in the vessel wall.In the present study, we hypothesized that cyclic flow variations (CFV) , resulting from recurrent arterial thrombosis and its dislodgement, is induced in stenosed carotid arteries in a rat model of chronic inhibition of NO synthesis.四组大鼠研究是研究：对照组，L组接受L名称，L+HYD组接受L名称和氢化嗪，L+A组接受L-NAME和ACE抑制剂Imidapril 4周。麻醉后，通过收缩暴露的颈动脉诱导狭窄，并使用超声流动证明CFV。对照组的CFV挑衅率为0％，L组为94％，L+HYD组为80％，L+ACE抑制剂组为0％。在L和L+HYD组中，颈动脉ACE活性增加，并在L = ACE抑制剂组中受到抑制。在单独的研究中，用凝血酶拮抗剂阿atroban进行治疗，但没有使用车辆或阿司匹林，几乎废除了CFV。群体中血小板计数的群体之间没有显着差异，对胶原蛋白的响应胶原蛋白的血小板聚集以及凝血级联指数（PT和APTT）的指标。可能会导致这种变化。