Cellular and Molecular Mechanism Coronary Spasm

1. 1）采用生物测定法测定了高胆固醇血症动脉粥样硬化兔（WHHL）主动脉内皮源性舒张因子（EFRF）的释放。我们发现动脉粥样硬化血管的松弛减弱是由于EFRF的产生受损和EFRF的失活所致。2）我们研究了带皂皮的血管平滑肌纤维的Ca^++-张力关系。从痉挛和非痉挛的冠状动脉部位切取的标本中的Ca^++-张力关系相似。3）我们在活体猪模型中研究了EDRF在冠状动脉痉挛原因中的作用。EDRF抑制剂（LNNA 1-3 mg/kg）增强了对照部位的阿托宁诱导的收缩，但在痉挛部位没有改变，表明阿托宁诱导的冠状动脉痉挛主要不是由内皮功能障碍引起的。2.我们在猪模型中检查了严重的冠状动脉痉挛是否会导致冠状动脉狭窄的进展，发现突然发作的冠状动脉痉挛会导致器质性狭窄和急性心肌梗死的急性进展。3.我们研究了变异型心绞痛患者的内皮依赖性血管舒张功能。结果表明，变异型心绞痛患者血管痉挛部位存在P物质诱发的内皮依赖性舒张反应。

1.Factors that mediate hypercontraction of atherosclerotic blood vessels1) We measured the release of endothelium-derived relaxing factor (EFRF) from aorta of hypercholesterolemic atherosclerotic rabbit (WHHL) using a bioassay technique. We found that attenuated relaxation of the atherosclerotic vessels resulted from both an impaired production of EFRF and inactivation of EFRF.2) We studied Ca^<++>-tension relationship in saponin-skinned vascular smooth fibers. The Ca^<++>-tension relationship was similar in preparations excised from the spastic and non-spastic coronary artery site.3) We studied the role of EDRF in the cause of coronary spasm in the swine model in vivo. An inhibitor of EDRF (LNNA 1-3 mg/kg) potentiated serotonin-induced constriction at the control site, but did not alter it in the spastic site, suggesting that serotonin-induced coronary spasm did not resulted primarily from endothelial dysfunction. 2. We examined whether intense coronary spasm causes progression of coronary stenosis in our swine model, and found that coronary spasm of abrupt onset resulted in acute progression of organic stenosis and acute myocardial infarction. 3. We studied endothelium-dependent vasodilation in patients with variant angina. The results indicated that endothelium-dependent vasodilation evoked with substance P was present at the vasospastic site in patients with variant angina.