Pretorius Mias, Rosenbaum David A, Lefebvre Jean, Vaughan Douglas E, Brown Nancy J
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232-6602, USA.
Hypertension. 2002 Mar 1;39(3):767-71. doi: 10.1161/hy0302.105767.
Bradykinin stimulates tissue plasminogen activator release from human endothelium through a flow-independent, B2 receptor-dependent mechanism. The present study tests the hypothesis that smoking impairs bradykinin-stimulated tissue plasminogen activator release. Graded doses of nitroprusside (1.6 to 6.4 microg/min), methacholine (3.2 to 12.8 microg/min), and bradykinin (100 to 400 ng/min) were infused in the brachial artery in random order in 20 smokers and 12 nonsmokers matched for age, gender, and body mass index. Forearm blood flow was measured by strain-gauge plethysmography. All 3 drugs caused a dose-dependent increase in forearm blood flow, with no significant difference between smokers and nonsmokers. Bradykinin (P=0.001) and methacholine (P=0.001) caused significant dose-dependent increases in net tissue plasminogen activator release. The tissue plasminogen activator response to bradykinin was significantly greater than the tissue plasminogen activator response to methacholine in the nonsmokers (maximal net tissue plasminogen activator release, 73.2+/-21.5 versus 27.6+/-7.2 ng/min per 100 mL; P=0.001) but not in the smokers (maximal net tissue plasminogen activator release, 44.5+/-10.7 versus 24.8+/-9.3 ng/min per 100 mL; P=0.154). The effect of bradykinin (P=0.037), but not methacholine (P=0.978), on net tissue plasminogen activator release was significantly reduced in smokers compared with nonsmokers. The vascular tissue plasminogen activator response to bradykinin, but not methacholine, is impaired in smokers. Stimulated tissue plasminogen activator release may be a more sensitive measure of endothelial function than vasodilation.
缓激肽通过一种不依赖血流、依赖B2受体的机制刺激人内皮细胞释放组织纤溶酶原激活物。本研究检验了吸烟会损害缓激肽刺激的组织纤溶酶原激活物释放这一假说。将不同剂量的硝普钠（1.6至6.4微克/分钟）、乙酰甲胆碱（3.2至12.8微克/分钟）和缓激肽（100至400纳克/分钟）以随机顺序注入20名年龄、性别和体重指数相匹配的吸烟者及12名不吸烟者的肱动脉。通过应变片体积描记法测量前臂血流量。所有这三种药物均引起前臂血流量呈剂量依赖性增加，吸烟者与不吸烟者之间无显著差异。缓激肽（P=0.001）和乙酰甲胆碱（P=0.001）引起净组织纤溶酶原激活物释放显著的剂量依赖性增加。在不吸烟者中，组织纤溶酶原激活物对缓激肽的反应显著大于对乙酰甲胆碱的反应（最大净组织纤溶酶原激活物释放量，每100毫升分别为73.2±21.5与27.6±7.2纳克/分钟；P=0.001），但在吸烟者中并非如此（最大净组织纤溶酶原激活物释放量，每100毫升分别为44.5±10.7与24.8±9.3纳克/分钟；P=0.154）。与不吸烟者相比，吸烟者中缓激肽（P=0.037）而非乙酰甲胆碱（P=0.978）对净组织纤溶酶原激活物释放的作用显著降低。吸烟者中血管组织纤溶酶原激活物对缓激肽而非乙酰甲胆碱的反应受损。与血管舒张相比，刺激组织纤溶酶原激活物释放可能是一种更敏感的内皮功能指标。
