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.
| Yipintsoi, Tada; Kroll, Keith; Bassingthwaighte, James B (2016) Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy. Am J Physiol Heart Circ Physiol 310:H351-64 |
| Farias 3rd, Martin; Gorman, Mark W; Savage, Margaret V et al. (2005) Plasma ATP during exercise: possible role in regulation of coronary blood flow. Am J Physiol Heart Circ Physiol 288:H1586-90 |
| Gorman, Mark W; Farias 3rd, Martin; Richmond, Keith N et al. (2005) Role of endothelin in alpha-adrenoceptor coronary vasoconstriction. Am J Physiol Heart Circ Physiol 288:H1937-42 |
| Tune, Johnathan D; Gorman, Mark W; Feigl, Eric O (2004) Matching coronary blood flow to myocardial oxygen consumption. J Appl Physiol 97:404-15 |
| Gorman, Mark W; Ogimoto, Kayoko; Savage, Margaret V et al. (2003) Nucleotide coronary vasodilation in guinea pig hearts. Am J Physiol Heart Circ Physiol 285:H1040-7 |
| Gorman, Mark W; Marble, David R; Ogimoto, Kayoko et al. (2003) Measurement of adenine nucleotides in plasma. Luminescence 18:173-81 |
| Tune, J D; Richmond, K N; Gorman, M W et al. (2001) K(ATP)(+) channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation. Am J Physiol Heart Circ Physiol 280:H868-75 |
| Tune, J D; Richmond, K N; Gorman, M W et al. (2000) Role of nitric oxide and adenosine in control of coronary blood flow in exercising dogs. Circulation 101:2942-8 |
| Richmond, K N; Tune, J D; Gorman, M W et al. (2000) Role of K(ATP)(+) channels and adenosine in the control of coronary blood flow during exercise. J Appl Physiol 89:529-36 |
| Tune, J D; Richmond, K N; Gorman, M W et al. (2000) Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise. Am J Physiol Heart Circ Physiol 278:H74-84 |
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