Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: Effects of angiotensin-converting enzyme inhibitors
Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: Effects of angiotensin-converting enzyme inhibitors
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DOI：
10.1016/s0735-1097(01)01202-5
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发表时间：
2001-05-01
影响因子：
24
通讯作者：
Kinoshita, M
中科院分区：
文献类型：
--
作者：
Minai, K;Matsumoto, T;Kinoshita, M
目的：本研究的目的是确定：1)缓激肽（BK）是否直接刺激人冠状动脉循环组织纤溶酶原激活物（tPA）的分泌，2)抑制血管紧张素转换酶（ACE）是否有利于改变BK调节的纤溶平衡。背景：缓激肽是内皮细胞tPA分泌的有效刺激剂；然而，BK对人体冠状动脉循环中tPA释放的影响尚未被研究。方法56例非典型胸痛患者随机分为2组：应用ACE抑制剂依那普利治疗25例（ACE抑制剂组），不应用ACE抑制剂治疗31例（非ACE抑制剂组）。将BK（0.2、0.6、2.0杯/分钟）、乙酰胆碱（ACh）（30杯/分钟）和罂粟碱（PA） （12 mg）等量滴入左冠状动脉。采用多普勒血流速度法测定冠状动脉血流（CBF）。从主动脉（Ao）和冠状窦（CS）取血。结果：缓激肽诱导两组CBF增加相似。BK诱导的tPA净释放量在两组均呈剂量依赖性增加，且ACE抑制剂组的增加幅度大于非ACE抑制剂组。缓激肽未改变两组Ao或CS中纤溶酶原激活物抑制剂-1 （PAI-1）水平。在两组中，乙酰胆碱和肾上腺素均未改变tPA水平和PAI-1水平。结论：冠状动脉内灌注BK可刺激tPA释放，但不会引起冠状动脉循环中PAI-1水平的变化。此外，BK的这种作用被ACE抑制剂增强。[J]中华医学会心脏科杂志，2001;37(3):366 - 366。
OBJECTIVES The goal of this study was to determine: 1) whether bradykinin (BK) directly stimulates tissue plasminogen activator (tPA) secretion in human coronary circulation, and 2) whether angiotensin-converting enzyme (ACE) inhibition favorably alters the fibrinolytic balance regulated by BK.BACKGROUND Bradykinin is a potent stimulator of tPA secretion in endothelial cells; however, the effect of BK on tPA release in the human coronary circulation has not been studied.METHODS Fifty-six patients with atypical chest pain were randomly assigned to two groups: 25 patients were treated with the ACE inhibitor enalapril (ACE inhibitor group), and 31 were not treated with ACE inhibitors (non-ACE inhibitor group). Graded doses of BK (0.2, 0.6, 2.0 mug/min), acetylcholine (ACh) (30 mug/min) and papaverine (PA) (12 mg) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS).RESULTS Bradykinin induced similar increases in CBF in both groups. The net tPA release induced by BK was dose-dependently increased in both groups, and the extent of that increase in the ACE inhibitor group was greater than that in the non-ACE inhibitor group. Bradykinin did not alter plasminogen activator inhibitor-1 (PAI-1) levels in the Ao or CS in either group. Neither ACh nor PA altered tPA levels or PAI-1 levels in either group.CONCLUSIONS Intracoronary infusion of BK stimulates tPA release without causing any change in PAI-1 levels in the human coronary circulation. In addition, this effect of BK is augmented by an ACE inhibitor. (J Am Coll Cardiol 2001;37:1565-70) (C) 2001 by the American College of Cardiology.