ADENOSINE & KATP CHANNEL CONTROL OF CORONARY BLOOD FLOW

腺苷

• 批准号: 6430399
• 负责人: ERIC O FEIGL
• 金额: $ 34.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-25 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6430399
• 关键词: adenosine; adenosine triphosphate; coronary vasodilator; coronary vessels; cytochrome P450; dogs; endothelin; erythrocytes; exercise; heart circulation; heart metabolism; heart pharmacology; microcirculation; oxygen consumption; potassium channel; purinergic receptor; vasodilation

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.

描述（由申请人提供）：当心率增加时（如发生）