Role of nitric oxide and adenosine in control of coronary blood flow in exercising dogs.
BACKGROUND
Inhibition of nitric oxide (NO) synthesis results in very little change in coronary blood flow, but this is thought to be because cardiac adenosine concentration increases to compensate for the loss of NO vasodilation. Accordingly, in the present study, adenosine measurements were made before and during NO synthesis inhibition during exercise.


RESULTS
Experiments were performed in chronically instrumented dogs at rest and during graded treadmill exercise before and during inhibition of NO synthesis with N(omega)-nitro-L-arginine (L-NNA, 35 mg/kg IV). Before inhibition of NO synthesis, myocardial oxygen consumption increased approximately 3.7-fold, and coronary blood flow increased approximately 3.2-fold from rest to the highest level of exercise, and this was not changed by NO synthesis inhibition. Coronary venous oxygen tension was modestly reduced by L-NNA at all levels of myocardial oxygen consumption. However, the slope of the relationship between myocardial oxygen consumption and coronary venous oxygen tension was not altered by L-NNA. Inhibition of NO synthesis did not increase coronary venous plasma or estimated interstitial adenosine concentration. During exercise, estimated interstitial adenosine remained well below the threshold concentration necessary for coronary vasodilation before or after L-NNA.


CONCLUSIONS
NO causes a modest coronary vasodilation at rest and during exercise but does not act as a local metabolic vasodilator. Adenosine does not mediate a compensatory local metabolic coronary vasodilation when NO synthesis is inhibited.
Tune
J D
JD
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195-7290, USA.
Richmond
K N
KN
Gorman
M W
MW
Feigl
E O
EO
D000241:Adenosine / Q000097:blood / Q000502:physiology*; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D014680:Veins
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D000241:Adenosine; D010100:Oxygen