Chiu P J, Vemulapalli S, Bryant R W
Biochem Pharmacol. 1986 Oct 15;35(20):3593-9. doi: 10.1016/0006-2952(86)90631-3.
In dogs undergoing 24- or 72-hr severe narrowing of the left anterior descending coronary artery (LAD), the in vitro formation of immunoreactive leukotriene C4 (LTC4) by the stenosed LAD was greatly augmented by 1 microM A23187 in a 10-min incubation at 37 degrees. This stimulated LTC4 formation was abolished by 30 microM nordihydroguaiaretic acid (NDGA). The incubation products were identified by high performance liquid chromatography and radioimmunoassay to be largely composed of LTC4 and LTD4 in similar proportion. In contrast to the stenosed LAD, the non-stenotic left circumflex coronary artery, apex of the heart, and renal artery of the same experimental animals failed to respond to the calcium ionophore up to 10 microM. The vascular and cardiac tissues from sham-operated animals also remained quiescent in the presence of A23187. The normal coronary artery showed low levels of leukotriene formation and was resistant to the ionophore. It is proposed that a latent portion of leukotriene synthesis, which can be triggered by the calcium ionophore, may play a significant role in the pathogenesis of coronary artery spasm associated with acute myocardial infarction and angina pectoris in patients with obstructive coronary artery disease.
在经历了左前降支冠状动脉(LAD)24小时或72小时严重狭窄的犬类中,在37摄氏度下孵育10分钟时,1微摩尔A23187可使狭窄的LAD体外免疫反应性白三烯C4(LTC4)的形成大幅增加。这种刺激的LTC4形成被30微摩尔去甲二氢愈创木酸(NDGA)消除。通过高效液相色谱和放射免疫测定法鉴定孵育产物,发现其主要由比例相似的LTC4和LTD4组成。与狭窄的LAD相反,同一实验动物的非狭窄左旋冠状动脉、心尖和肾动脉对高达10微摩尔的钙离子载体无反应。假手术动物的血管和心脏组织在A23187存在下也保持静止。正常冠状动脉显示出低水平的白三烯形成,并且对离子载体有抗性。有人提出,白三烯合成的潜在部分可由钙离子载体触发,这可能在患有阻塞性冠状动脉疾病的患者急性心肌梗死和心绞痛相关的冠状动脉痉挛发病机制中起重要作用。