Newby D E, Wright R A, Ludlam C A, Fox K A, Boon N A, Webb D J
Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Scotland, UK.
Thromb Haemost. 1997 Oct;78(4):1242-8.
The effects on blood flow and plasma fibrinolytic and coagulation parameters of intraarterial substance P, an endothelium dependent vasodilator, and sodium nitroprusside, a control endothelium independent vasodilator, were studied in the human forearm circulation. At subsystemic locally active doses, both substance P (2-8 pmol/min) and sodium nitroprusside (2-8 microg/min) caused dose-dependent vasodilatation (p <0.001 for both) without affecting plasma concentrations of PAI-1, von Willebrand factor antigen or factor VIII:C activity. Substance P caused local increases in t-PA antigen and activity (p <0.001) in the infused arm while sodium nitroprusside did not. At higher doses, substance P increased blood flow and t-PA concentrations in the noninfused arm. We conclude that brief, locally active and subsystemic infusions of intraarterial substance P cause a rapid and substantial local release of t-PA which appear to act via a flow and nitric oxide independent mechanism. This model should provide a useful and selective method of assessing the in vivo capacity of the forearm endothelium to release t-PA acutely.
在人体前臂循环中，研究了内皮依赖性血管舒张剂动脉内注入P物质和对照性内皮非依赖性血管舒张剂硝普钠对血流、血浆纤维蛋白溶解和凝血参数的影响。在低于全身活性的局部活性剂量下，P物质（2 - 8 pmol/分钟）和硝普钠（2 - 8 μg/分钟）均引起剂量依赖性血管舒张（两者p均<0.001），且不影响血浆PAI - 1、血管性血友病因子抗原或因子VIII:C活性的浓度。P物质使注入臂的组织型纤溶酶原激活物（t - PA）抗原和活性局部增加（p <0.001），而硝普钠则无此作用。在较高剂量时，P物质增加了未注入臂的血流和t - PA浓度。我们得出结论，动脉内短暂、局部活性和低于全身活性的P物质注入会导致t - PA迅速大量局部释放，其作用似乎通过与血流和一氧化氮无关的机制。该模型应提供一种有用且具选择性的方法来评估前臂内皮急性释放t - PA的体内能力。
