Endogenous adenosine and coronary vasoconstriction in hypoperfused myocardium during exercise.
OBJECTIVE
The coronary circulation has been shown to remain responsive to vasodilator and vasoconstrictor stimuli during myocardial ischaemia. The aim of this study was to investigate whether endogenous adenosine attenuates coronary vasoconstriction caused by the thromboxane A2 analogue, U46619.


METHODS
Nine chronically instrumented dogs were studied during treadmill exercise in the presence of a coronary stenosis which resulted in distal left circumflex coronary artery hypoperfusion. Myocardial blood flow was assessed with radioactive microspheres during exercise prior to and during intracoronary infusion of U46619 (0.01 microgram.kg-1 x min-1), in the absence and the presence of adenosine receptor blockade with intravenous 8-phenyltheophylline (5 mg.kg-1) and intracoronary adenosine deaminase (50 units.kg-1). Distal coronary pressure was maintained constant during the control stenosis and the three interventions, at 49(SEM 3), 50(3), 50(3), and 50(3) mm Hg.


RESULTS
During control exercise mean myocardial blood flow was 0.91(0.09) ml.min-1 x g-1 in the stenosis region and 2.54(0.28) in the normal region. With no change in distal coronary pressure, U46619 decreased mean myocardial blood flow to 0.70(0.10) ml.min-1 x g-1 (p < 0.05). Adenosine blockade alone decreased myocardial blood flow in the stenosis region to 0.60(0.07) ml.min-1 x g-1 (p < 0.05 v control stenosis), indicating that endogenous adenosine contributed to coronary vasodilatation in the ischaemic region. However, adenosine blockade did not augment the vasoconstriction in response to U46619 [mean myocardial blood flow 0.49(0.05) ml.min-1 x g-1], indicating that endogenous adenosine did not attenuate the vasoconstriction caused by U46619.


CONCLUSIONS
Endogenous adenosine contributed to dilatation of resistance vessels in hypoperfused myocardium of exercising dogs in the absence as well as in the presence of U46619. However, endogenous adenosine did not attenuate the magnitude of the vasoconstrictor response to U46619. These findings are best explained by observations that thromboxane A2 and adenosine act on coronary vascular segments of different size.
Duncker
D J
DJ
Department of Internal Medicine, University of Minnesota Medical School, Minneapolis 55455.
Laxson
D D
DD
Lindstrom
P
P
Bache
R J
RJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000241:Adenosine / Q000502:physiology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004285:Dogs; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology*; D005082:Physical Exertion / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine