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Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise
J D Tune1, K N Richmond, M W Gorman
1Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Insights
Adenosine does not regulate coronary blood flow during exercise in dogs. This study found no evidence that adenosine plays a role in exercise-induced coronary hyperemia, challenging previous assumptions about local metabolic control.
Area of Science:
- Cardiovascular Physiology
- Exercise Physiology
- Pharmacology
Background:
- Coronary exercise hyperemia is the increase in blood flow to the heart muscle during physical activity.
- Adenosine is a nucleoside that has been implicated as a potential mediator of local metabolic control of coronary blood flow.
- Understanding the precise mechanisms regulating coronary blood flow during exercise is crucial for cardiovascular health.
Purpose of the Study:
- To quantitatively assess the role of adenosine in mediating coronary exercise hyperemia in a canine model.
- To investigate whether adenosine acts as a local metabolic regulator of coronary blood flow during exercise.
Main Methods:
- Dogs were instrumented to measure cardiac hemodynamics and coronary blood flow.
- Cardiac interstitial adenosine concentration was estimated using a mathematical model.
- Adenosine receptor blockade was performed using 8-phenyltheophylline (8-PT) or 8-p-sulfophenyltheophylline (8-PST) during rest and graded treadmill exercise.
Main Results:
- Exercise significantly increased myocardial oxygen consumption and coronary blood flow, but not mean aortic pressure.
- Estimated interstitial adenosine concentration did not rise sufficiently during exercise to suggest a role in vasodilation.
- Adenosine receptor blockade did not affect resting or exercise-induced changes in myocardial oxygen consumption or coronary blood flow.
Conclusions:
- Adenosine is not responsible for the local metabolic control of coronary blood flow in dogs during exercise.
- The findings challenge the hypothesis that adenosine acts as a high-gain, negative-feedback regulator of coronary blood flow during physical exertion.
Abstract:
The purpose of this investigation was to quantitatively evaluate the role of adenosine in coronary exercise hyperemia. Dogs (n = 10) were chronically instrumented with catheters in the aorta and coronary sinus, and a flow probe on the circumflex coronary artery. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous plasma concentrations using a previously tested mathematical model. Coronary blood flow, myocardial oxygen consumption, heart rate, and aortic pressure were measured at rest and during graded treadmill exercise with and without adenosine receptor blockade with either 8-phenyltheophylline (8-PT) or 8-p-sulfophenyltheophylline (8-PST). In control vehicle dogs, exercise increased myocardial oxygen consumption 4.2-fold, coronary blood flow 3.8-fold, and heart rate 2.5-fold, whereas mean aortic pressure was unchanged. Coronary venous plasma adenosine concentration was little changed with exercise, and the estimated interstitial adenosine concentration remained well below the threshold for coronary vasodilation. Adenosine receptor blockade did not significantly alter myocardial oxygen consumption or coronary blood flow at rest or during exercise. Coronary venous and estimated interstitial adenosine concentration did not increase to overcome the receptor blockade with either 8-PT or 8-PST as would be predicted if adenosine were part of a high-gain, negative-feedback, local metabolic control mechanism. These results demonstrate that adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise.
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