ADENOSINE & KATP CHANNEL CONTROL OF CORONARY BLOOD FLOW

描述（由申请人提供）：当心率增加时（如发生 在运动期间），冠状动脉血流量必须增加，以提供氧气， 心脏，以支持增加的心肌耗氧量。的目的 这项研究的目的是为了发现基本的生理机制 将冠状动脉血流量与心肌耗氧量联系起来。没有这些 一旦发生心肌缺血，心脏就会死亡。一个新的假设， 支持数据，其中ATP从红细胞中释放， 冠状循环作为局部代谢冠状动脉的介质 血管舒张提出了一个定量检验ATP假说的方案 在心动过速和运动期间，结合ATP测量和 ATP受体阻断剂。假设内皮素血管收缩在 左心室的外层有助于维持血液流向脆弱的人 在运动过程中的内层将通过测量血浆 内皮素水平和内皮素受体阻断剂。假定的角色 P-450酶作用于心脏中的花生四烯酸， 一种名为依地平和二氢叶酸的强效冠状血管扩张剂化合物将被测试 测量这些化合物和选择性封闭剂。的 建议的基础研究是理解正常冠状动脉的基础。 冠状动脉疾病的生理学基础。

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.