ADENOSINE & KATP CHANNEL CONTROL OF CORONARY BLOOD FLOW

描述(申请人提供)：当心率增加时(如发生 在运动中)，冠脉血流量必须增加，以提供氧气给 心脏支持增加的心肌耗氧量。目的 建议的研究是为了发现其基本的生理机制。 冠脉血流量与心肌耗氧量之间的关系。如果没有这些 机制，心脏就会变得缺血并死亡。一种新的假设， 提供了支持数据，其中从红细胞释放的ATP在 冠脉循环是局部代谢性冠状动脉病变的中介 血管扩张。提出了一种定量检验ATP假说的方案。 在心动过速和运动中，结合ATP测量和 三磷酸腺苷受体阻断。内皮素对血管收缩作用的假说 左心室的外层有助于维持流向脆弱人群的血液 运动中的内层将通过测量血浆进行测试 内皮素水平和内皮素受体阻滞剂。假定的角色 作用于心脏中花生四烯酸的P-450酶产生极 将测试被称为EETs和DHETs的强大的冠状动脉血管扩张剂化合物 通过测量这些化合物和选择性封闭剂。这个 提出的基础研究是了解正常冠状动脉的基础 冠脉疾病的基础生理学。

DESCRIPTION (provided by applicant): When heart rate increases (as occurs during exercise), coronary blood flow must increase to provide oxygen to the heart to support the augmented myocardial oxygen consumption. The purpose of the proposed research is to discover the essential physiological mechanisms that couple coronary blood flow to myocardial oxygen consumption. Without these mechanisms, the heart becomes ischemic and dies. A new hypothesis, with supporting data, is presented where ATP released from red blood cells in the coronary circulation acts as the mediator of local metabolic coronary vasodilation. A plan is presented to quantitatively test the ATP hypothesis during tachycardia and exercise with a combination of ATP measurements and ATP-receptor blockade. The hypothesis that endothelin vasoconstriction in the outer layers of the left ventricle helps sustain blood flow to the vulnerable inner layers during exercise will be tested with measurements of plasma endothelin levels and endothelin receptor-blocking agents. The postulated role of P-450 enzymes acting on arachidonic acid in the heart to produce extremely powerful coronary vasodilator compounds called EETs and DHETs will be tested with measurements of these compounds and selective blocking agents. The proposed basic research is fundamental to understanding the normal coronary physiology that underlies coronary artery disease.