(Circulation. 2000;101:2942.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Role of Nitric Oxide and Adenosine in Control of Coronary Blood Flow in Exercising Dogs
From the Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle.
Correspondence to Eric O. Feigl, MD, Department of Physiology and Biophysics, University of Washington School of Medicine, Box 357290, Seattle, WA 98195-7290.
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.
Methods and Results—Experiments were performed in chronically
instrumented dogs at rest and during graded treadmill exercise before
and during inhibition of NO synthesis with
N
-nitro-L-arginine
(L-NNA, 35 mg/kg IV). Before inhibition of NO synthesis,
myocardial oxygen consumption increased 
3.7-fold, and
coronary blood flow increased 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.
Key Words: nitric oxide • adenosine • coronary disease • exercise
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