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 运动期间），冠状动脉血流量必须增加才能为心脏提供氧气 心脏以支持增加的心肌耗氧量。目的 拟议的研究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耦合起来。没有这些 机制，心脏缺血并死亡。一个新的假设，与 支持数据，其中 ATP 从红细胞中释放 冠状动脉循环充当冠状动脉局部代谢的介质 血管舒张。提出了定量检验 ATP 假设的计划 在心动过速和运动期间结合 ATP 测量和 ATP 受体阻断。内皮素有血管收缩作用的假说 左心室的外层有助于维持流向弱势群体的血液 运动期间的内层将通过血浆测量进行测试 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，产生极其 将测试称为 EET 和 DHET 的强效冠状血管扩张化合物 测量这些化合物和选择性封闭剂。的 拟议的基础研究对于了解正常冠状动脉至关重要 冠状动脉疾病的生理学。

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.