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 a denosine concentration increases to compensate for the loss of NO vasodilat ion. Accordingly, in the present study, adenosine measurements were made be fore 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 inhibit ion of NO synthesis with N-omega-nitro-L-arginine (L-NNA, 35 mg/kg IV). Bef ore inhibition of NO synthesis, myocardial oxygen consumption increased app roximate to 3.7-fold, and coronary blood flow increased approximate to 3.2- fold from rest to the highest level of exercise, and this was not changed b y NO synthesis inhibition. Coronary venous oxygen tension was modestly redu ced by L-NNA at all levels of myocardial oxygen consumption. However, the s lope 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 adenosin e 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 exe rcise but does not act as a local metabolic vasodilator. Adenosine does not mediate a compensatory local metabolic coronary vasodilation when NO synth esis is inhibited.