Related Experiment Video
Updated: Jun 8, 2026

Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine
Published on: February 9, 2016
Adenine nucleotide control of coronary blood flow during exercise
Mark W Gorman1, G Alec Rooke, Margaret V Savage
1Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195-7290, USA.
Insights
Adenosine triphosphate (ATP) and its breakdown products regulate coronary blood flow during exercise. Blocking purinergic receptors disrupts this balance, supporting ATP
Area of Science:
- Cardiovascular Physiology
- Metabolic Regulation
- Purinergic Signaling
Background:
- The adenine nucleotide hypothesis suggests ATP, ADP, and AMP regulate coronary blood flow via purinergic receptors.
- Previous work showed increased coronary venous ATP during exercise correlates with blood flow.
Purpose of the Study:
- To test the adenine nucleotide hypothesis by examining oxygen delivery versus consumption balance during exercise.
- To investigate the role of purinergic receptors in this regulatory mechanism.
Main Methods:
- Experiments conducted on chronically instrumented dogs (n=7).
- Measurements included aortic/coronary sinus catheters and circumflex coronary artery flow transducer.
- Assessed oxygen delivery-consumption balance before and after purinergic receptor blockade and nitric oxide inhibition during exercise.
Main Results:
- During exercise, myocardial oxygen consumption increased, and oxygen delivery-consumption balance declined, indicated by lower coronary venous oxygen tension.
- Blockade of P1 and P2Y(1) purinergic receptors and nitric oxide synthesis inhibition significantly worsened the oxygen delivery-consumption balance compared to control.
Conclusions:
- Results support the adenine nucleotide hypothesis.
- ATP and its metabolites (ADP, AMP) are integral to the negative feedback system matching coronary blood flow to myocardial oxygen demand at rest and during exercise.
Abstract:
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.
Related Concept Videos
Pathophysiology of Cardiac Performance
Antianginal Drugs: Nitrates and β-Blockers
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow. Administered...
Regulation of Heart Rates
The SNS increases heart rate through the release of norepinephrine and epinephrine, which act on beta-1 adrenergic receptors in the heart. This action increases the rate of depolarization in the sinoatrial (SA) node, the heart's...
Autoregulation of Blood Flow
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation.
Nitric Oxide Signaling Pathway
Exercise and Cardiovascular Response
Light to moderate physical activity initiates a series of interconnected responses in the body. The heart rate modestly increases in anticipation of the workout, followed by widespread vasodilation as oxygen consumption by skeletal muscles increases. This results in decreased peripheral resistance, increased capillary blood flow, and accelerated...

