Adenine nucleotide control of coronary blood flow during exercise.
The adenine nucleotide hypothesis postulates that the ATP released from red blood cells is broken down to ADP and AMP in coronary capillaries and that ATP, ADP, and AMP act on purinergic receptors on the surface of capillary endothelial cells. Purinergic receptor activation initiates a retrograde conducted vasodilator signal to the upstream arteriole that controls coronary blood flow in a negative feedback manner. A previous study (M. Farias 3rd, M. W. Gorman, M. V. Savage, and E. O. Feigl, Am J Physiol Heart Circ Physiol 288: H1586-H1590, 2005) demonstrated that coronary venous plasma ATP concentration increased during exercise and correlated with coronary blood flow. The present experiments test the adenine nucleotide hypothesis by examining the balance between oxygen delivery (via coronary blood flow) and myocardial oxygen consumption during exercise before and after purinergic receptor blockade. Dogs (n = 7) were chronically instrumented with catheters in the aorta and coronary sinus and a flow transducer around the circumflex coronary artery. During control treadmill exercise, myocardial oxygen consumption increased and the balance between oxygen delivery and myocardial oxygen consumption fell as indicated by a declining coronary venous oxygen tension. Blockade of P1 and P2Y(1) purinergic receptors combined with inhibition of nitric oxide synthesis significantly decreased the balance between oxygen delivery and myocardial oxygen consumption compared with control. The results support the hypothesis that ATP and its breakdown products ADP and AMP are part of a negative feedback control mechanism that matches coronary blood flow to myocardial oxygen consumption at rest and during exercise.
Gorman
Mark W
MW
Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195-7290, USA.
Rooke
G Alec
GA
Savage
Margaret V
MV
Jayasekara
M P Suresh
MP
Jacobson
Kenneth A
KA
Feigl
Eric O
EO
D000227:Adenine Nucleotides / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D005082:Physical Exertion; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1 / Q000187:drug effects / Q000378:metabolism*; D012039:Regional Blood Flow
D000227:Adenine Nucleotides; D004791:Enzyme Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D058921:Purinergic P2Y Receptor Antagonists; D018047:Receptors, Purinergic P1; D058472:Receptors, Purinergic P2Y1; D009569:Nitric Oxide; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D010100:Oxygen