Kozai T, Shimokawa H, Yamawaki T, Fukumoto Y, Kadokami T, Kuwata K, Katsumata N, Egashira K, Takeshita A
Research Institute of Angiocardiology, Fukuoka, Japan.
Coron Artery Dis. 1997 Jul;8(7):423-32. doi: 10.1097/00019501-199707000-00004.
Although platelet activating factor (PAF) is an important vasoactive substance released from activated leukocytes, platelets and endothelial cells, little is known about its effect at the inflammatory coronary lesions in vivo.
To examine the coronary vasomotor responses to PAF at the inflammatory lesions in our swine model with interleukin-1 beta (IL-1 beta) in vivo.
Under aseptic conditions, the proximal segment of the porcine left coronary artery was dissected and wrapped with cotton mesh absorbing IL-1 beta. Two weeks after the operation, coronary vasomotion in response to intracoronary administration of 0.3 and 1 microgram/kg PAF, 1, 3, and 10 micrograms/kg serotonin, 1, 3 and 10 micrograms/kg histamine, and 5 and 50 micrograms/kg prostaglandin F2 alpha was examined by coronary arteriography.
At the IL-1 beta-treated site, PAF, serotonin and histamine, but not prostaglandin F2 alpha, caused hyperconstriction (n = 8). A synergy of the vasoconstricting effects of PAF and serotonin was also noted (n = 6). Administration of TCV-309, a selective PAF receptor antagonist, abolished the hyperconstrictive responses to PAF but not those to other agonists (n = 6). The PAF-induced coronary hyperconstrictions were significantly inhibited by administrations of the protein kinase C inhibitors staurosporine and sphingosine, but not by administrations of ryanodine, thapsigargin, or indomethacin (n = 4 each).
These results indicate that PAF causes hyperconstriction at the inflammatory coronary lesions in vivo by itself as well as in a synergistic manner with serotonin and that the PAF-induced hyperconstrictions are substantially mediated by a protein kinase C-dependent pathway in vivo.
尽管血小板活化因子（PAF）是一种从活化的白细胞、血小板和内皮细胞释放的重要血管活性物质，但关于其在体内炎症性冠状动脉病变中的作用知之甚少。
在我们的体内白细胞介素-1β（IL-1β）猪模型中，研究炎症病变处PAF对冠状动脉血管运动的反应。
在无菌条件下，解剖猪左冠状动脉近端并用吸收IL-1β的棉网包裹。术后两周，通过冠状动脉造影检查冠状动脉对冠状动脉内注射0.3和1微克/千克PAF、1、3和10微克/千克5-羟色胺、1、3和10微克/千克组胺以及5和50微克/千克前列腺素F2α的血管运动反应。
在IL-1β处理部位，PAF、5-羟色胺和组胺可引起血管过度收缩（n = 8），但前列腺素F2α无此作用。还观察到PAF和5-羟色胺的血管收缩作用具有协同作用（n = 6）。给予选择性PAF受体拮抗剂TCV-309可消除对PAF的过度收缩反应，但对其他激动剂无此作用（n = 6）。蛋白激酶C抑制剂星形孢菌素和鞘氨醇可显著抑制PAF诱导的冠状动脉过度收缩，但雷尼丁、毒胡萝卜素或吲哚美辛则无此作用（每组n = 4）。
这些结果表明，PAF自身以及与5-羟色胺协同作用可在体内炎症性冠状动脉病变处引起血管过度收缩，且PAF诱导的过度收缩在体内主要由蛋白激酶C依赖性途径介导。
