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ROLE OF MICROVASCULAR DISORDERS IN THE PATHOGENESIS OF MYOCARDIAL ISCHEMIA

微血管疾病在心肌缺血发病机制中的作用

基本信息

批准号：
06404034
负责人：
TAKESHITA Akira
金额：
$ 11.58万
依托单位：
KYUSHU UNIVERSITY FACULTY OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

We have created animal models of microvascular disorders. Long-term inhibition of nitric oxide synthase with administering chronically an nitric oxide inhibitor (N^<omega>-nitro-L-arginine methyl ester, L-NAME) to rats and pigs caused coronary vascular structural changes (medial thickening and perivascular fibrosis). We examined whether microvascular responses to serotonin is altered in the pig model. After anesthesia, we infused serotonin into the coronary artery and found that the drug significantly decreased coronary blood flow in the L-NAME treated pigs but not in the control pigs.the vasomotor response to serotonin was similar between the two groups. Thus, these data suggest that the enhanced decrease in coronary blood flow to serotonin was due to augmented constriction of microvessels.We aimed to provoke myocardial ischemia in the pig model. We administered papaverine into the coronary artery and found that the drug induced myocardial ischemia (myocardial lactate production). Because the papaverine-induced myocardial ischemia was associated with increased coronary blood flow, we concluded that the papaverine-induced myocardial ischemia was caused by altered distribution of regional myocardial blood flow.We examined effects of L-arginine administration on endothelium-dependent coronary vasodilation in patients with microvascular angina and found that L-arginine supplementation improved acetylcholine-induced endothelium-dependent vasodilation in those patients. We also explored to determined the mechanism of bradykinin-induced coronary vasodilation in humans. We found that the bradykinin-induced coronary vasodilation was nearly completely inhibited by an inhibitor of NO synthesis and markedly augmented by an angiotensin-converting enzyme inhibitor enalaprilat.

我们创建了微血管疾病的动物模型。对大鼠和猪长期施用一氧化氮抑制剂（N^O-硝基-L-精氨酸甲酯，L-NAME）对一氧化氮合酶的长期抑制导致冠状血管结构变化（内侧增厚和血管周围纤维化）。我们检查了猪模型中微血管对血清素的反应是否发生改变。麻醉后，我们将血清素注入冠状动脉，发现该药物显着降低了 L-NAME 治疗猪的冠状动脉血流量，但对照组猪则没有。两组之间对血清素的血管舒缩反应相似。因此，这些数据表明，流向血清素的冠状动脉血流的增加减少是由于微血管收缩增强所致。我们的目的是在猪模型中引发心肌缺血。我们将罂粟碱注入冠状动脉，发现该药物会引起心肌缺血（心肌乳酸产生）。由于罂粟碱引起的心肌缺血与冠状动脉血流量增加有关，因此我们得出结论，罂粟碱引起的心肌缺血是由局部心肌血流分布改变引起的。我们检查了L-精氨酸给药对微血管心绞痛患者内皮依赖性冠状动脉舒张的影响，发现补充L-精氨酸可以改善这些患者中乙酰胆碱诱导的内皮依赖性血管舒张。我们还探索确定了缓激肽诱导人类冠状动脉舒张的机制。我们发现，缓激肽诱导的冠状血管舒张几乎完全被NO合成抑制剂抑制，而血管紧张素转换酶抑制剂依那普利拉则显着增强。