Kuga T, Egashira K, Mohri M, Tsutsui H, Harasawa Y, Urabe Y, Ando S, Shimokawa H, Takeshita A
Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Circulation. 1995 Jul 15;92(2):183-9. doi: 10.1161/01.cir.92.2.183.
Bradykinin causes endothelium-dependent vasodilation of isolated human coronary arteries in vitro. However, the effect of bradykinin on vasomotion of human coronary arteries in vivo has not been studied. The aim of this study was to examine whether bradykinin-induced vasodilation is altered at the atherosclerotic or spastic site of human coronary arteries in vivo.
The effect of bradykinin on vasomotion of epicardial coronary arteries was evaluated in 8 patients with normal coronary arteries (control group), 14 patients with organic coronary stenosis (coronary artery disease [CAD] group), and 8 patients with vasospastic angina (VSA group). Changes in the diameter of epicardial coronary artery were assessed by quantitative coronary arteriography. Intracoronary administration of bradykinin at graded doses (60, 200, and 600 ng) dilated epicardial coronary arteries without altering arterial pressure or heart rate in all patients of either group. In the control group, vasomotor responses of the site where acetylcholine caused dilation were compared with the responses of the site where acetylcholine caused constriction. The magnitudes of bradykinin-induced dilation at the site with acetylcholine-induced dilation (mean +/- SD: 6 +/- 6%, 11 +/- 9%, and 15 +/- 9%) were comparable to that (3 +/- 6%, 8 +/- 8%, and 13 +/- 9%) at the site with acetylcholine-induced constriction. In the CAD group, vasomotor responses of the stenotic site (% diameter stenosis, 15% to 50%) and nonstenotic site were examined. The bradykinin-induced dilation at the stenotic site (0 +/- 4%, 3 +/- 8%, and 5 +/- 9%) was significantly less (P < .01) than at the nonstenotic site (3 +/- 4%, 8 +/- 6%, and 16 +/- 11%) and in the control group. Coronary vasodilation with nitrate at the stenotic site (20 +/- 11%) was comparable to that at the nonstenotic site (22 +/- 16%) and in the control group (21 +/- 10%). In the VSA group, vasomotor responses of the site with acetylcholine-induced spasm and the site without spasm were examined. The bradykinin-induced vasodilation at the spastic site (5 +/- 5%, 16 +/- 15%, and 33 +/- 17%) was comparable to that at the nonspastic site (4 +/- 8%, 12 +/- 14%, and 21 +/- 9%). Nitrate-induced dilation was comparable at the spastic site (51 +/- 19%) and the nonspastic site (32 +/- 13%). The ratio of bradykinin-induced vasodilation to nitrate-induced vasodilation at the spastic site was comparable to the control group.
These results suggest that bradykinin causes vasodilation of human epicardial coronary arteries in vivo and that bradykinin-induced endothelium-dependent vasodilation is impaired at the stenotic site but is preserved at the angiographically normal site where endothelium-dependent vasodilation by acetylcholine is impaired and at the spastic site.
缓激肽在体外可引起人离体冠状动脉的内皮依赖性血管舒张。然而，缓激肽对人冠状动脉体内血管运动的影响尚未得到研究。本研究的目的是检验缓激肽诱导的血管舒张在人冠状动脉体内的动脉粥样硬化或痉挛部位是否发生改变。
在8例冠状动脉正常的患者（对照组）、14例器质性冠状动脉狭窄患者（冠状动脉疾病[CAD]组）和8例变异性心绞痛患者（VSA组）中评估缓激肽对心外膜冠状动脉血管运动的影响。通过定量冠状动脉造影评估心外膜冠状动脉直径的变化。在两组所有患者中，冠状动脉内给予不同剂量（60、200和600 ng）的缓激肽可使心外膜冠状动脉扩张，且不改变动脉血压或心率。在对照组中，比较了乙酰胆碱引起扩张部位与引起收缩部位的血管运动反应。乙酰胆碱诱导扩张部位缓激肽诱导的扩张幅度（均值±标准差：6±6%、11±9%和15±9%）与乙酰胆碱诱导收缩部位的扩张幅度（3±6%、8±8%和13±9%）相当。在CAD组中，检查了狭窄部位（狭窄程度为15%至50%）和非狭窄部位的血管运动反应。狭窄部位缓激肽诱导的扩张（0±4%、3±8%和5±9%）显著低于非狭窄部位（3±4%、8±6%和16±11%）以及对照组（P<0.01）。狭窄部位硝酸酯类药物引起的冠状动脉扩张（20±11%）与非狭窄部位（22±16%）及对照组（21±10%）相当。在VSA组中，检查了乙酰胆碱诱导痉挛部位和无痉挛部位的血管运动反应。痉挛部位缓激肽诱导的血管舒张（5±5%、16±15%和33±17%）与非痉挛部位（4±8%、12±14%和
