title: Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise.
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.
authors.affiliation: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Tune
authors.forename: K N
authors.initials: KN
authors.lastname: Richmond
authors.forename: M W
authors.initials: MW
authors.lastname: Gorman
authors.forename: R A
authors.initials: RA
authors.lastname: Olsson
authors.forename: E O
authors.initials: EO
authors.lastname: Feigl
mesh_terms: D000241:Adenosine / Q000502:physiology*; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D011725:Pyridines / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D011725:Pyridines; D017466:Receptors, Endothelin; D013777:Tetrazoles; C120582:tezosentan; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine