Alpha-thrombin-induced pulmonary vasoconstriction.
Alpha-thrombin-induced pulmonary vasoconstriction.
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α-凝血酶诱导的肺血管收缩。
DOI：
10.1152/jappl.1987.63.5.1993
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Malik,AB
中科院分区：
文献类型：
--
作者：
Horgan,MJ;Fenton2nd,JW;Malik,AB
我们研究了凝血酶对离体豚鼠肺灌注林格氏白蛋白（0.5% g/100 ml）肺血管张力的直接影响。注射α-凝血酶（天然酶）导致肺动脉压（Ppa）和肺毛细血管压（Ppc）快速剂量依赖性增加，这与肺流出物血栓素B2浓度增加相关。Ppa和Ppc反应随时间降低，但在注射凝血酶后40分钟内再次增加。PPC的增加主要是毛细血管后血管收缩的结果。凝血酶注射后90分钟内发生肺水肿，表现为肺重量显著增加（较基线增加60%）。注射修饰的凝血酶（即，缺乏纤维蛋白原识别位点的γ-凝血酶或缺乏丝氨酸蛋白水解位点的i-Pr 2 P-α-凝血酶）与肺血流动力学或体重变化无关，也不阻断α-凝血酶的作用。吲哚美辛（环氧合酶抑制剂）、达唑昔苯（血栓烷合酶抑制剂）或水蛭素（凝血酶拮抗剂）抑制凝血酶诱导的肺血管收缩以及肺水肿。我们的结论是，凝血酶诱导的肺血管收缩主要是毛细血管后血管收缩的结果，并介导的反应是由环氧合酶衍生的代谢产物的产生。水肿的形成也依赖于环氧合酶途径的激活。α-凝血酶的蛋白水解位点是肺血管收缩和水肿反应所必需的。
We examined the direct effects of thrombin on pulmonary vasomotor tone in isolated guinea pig lungs perfused with Ringer albumin (0.5% g/100 ml). The injection of alpha-thrombin (the native enzyme) resulted in rapid dose-dependent increases in pulmonary arterial pressure (Ppa) and pulmonary capillary pressure (Ppc), which were associated with an increase in the lung effluent thromboxane B2 concentration. The Ppa and Ppc responses decreased with time but then increased again within 40 min after thrombin injection. The increases in Ppc were primarily the result of postcapillary vasoconstriction. Pulmonary edema as evidenced by marked increases (60% from base line) in lung weight occurred within 90 min after thrombin injection. Injection of modified thrombins (i.e., gamma-thrombin lacking the fibrinogen recognition site or i-Pr2P-alpha-thrombin lacking the serine proteolytic site) was not associated with pulmonary hemodynamic or weight changes nor did they block the effects of alpha-thrombin. Indomethacin (a cyclooxygenase inhibitor), dazoxiben (a thromboxane synthase inhibitor), or hirudin (a thrombin antagonist) inhibited the thrombin-induced pulmonary vasoconstriction, as well as the pulmonary edema. We conclude that thrombin-induced pulmonary vasoconstriction is primarily the result of constriction of postcapillary vessels, and the response is mediated by generation of cyclooxygenase-derived metabolites. The edema formation is also dependent on activation of the cyclooxygenase pathway. The proteolytic site of alpha-thrombin is required for the pulmonary vasoconstrictor and edemogenic responses.