Minai K, Matsumoto T, Horie H, Ohira N, Takashima H, Yokohama H, Kinoshita M
First Department of Internal Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Japan.
J Am Coll Cardiol. 2001 May;37(6):1565-70. doi: 10.1016/s0735-1097(01)01202-5.
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.
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.
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 microg/min), acetylcholine (ACh) (30 microg/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).
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.
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.
本研究的目的是确定：1）缓激肽（BK）是否直接刺激人体冠状动脉循环中组织型纤溶酶原激活物（tPA）的分泌，以及2）血管紧张素转换酶（ACE）抑制是否能有利地改变由BK调节的纤溶平衡。
缓激肽是内皮细胞中tPA分泌的有效刺激物；然而，BK对人体冠状动脉循环中tPA释放的影响尚未得到研究。
56例非典型胸痛患者被随机分为两组：25例患者接受ACE抑制剂依那普利治疗（ACE抑制剂组），31例未接受ACE抑制剂治疗（非ACE抑制剂组）。将不同剂量的BK（0.2、0.6、2.0微克/分钟）、乙酰胆碱（ACh）（30微克/分钟）和罂粟碱（PA）（12毫克）注入左冠状动脉。通过多普勒流速测量评估冠状动脉血流（CBF）。从主动脉（Ao）和冠状窦（CS）采集血样。
两组中BK引起的CBF增加相似。两组中BK诱导的tPA净释放均呈剂量依赖性增加，且ACE抑制剂组的增加程度大于非ACE抑制剂组。BK在两组中均未改变Ao或CS中的纤溶酶原激活物抑制剂-1（PAI-1）水平。ACh和PA在两组中均未改变tPA水平或PAI-1水平。
冠状动脉内注入BK可刺激tPA释放，而不会导致人体冠状动脉循环中PAI-1水平发生任何变化。此外，BK的这种作用会被ACE抑制剂增强。
