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—We previously reported that combined blockade of adenosine receptors and ATP-sensitive K+ channels (K⁺_ATP channels) blunted but did not abolish the response of coronary blood flow to exercise. This study tested the hypothesis that the residual increase in coronary flow in response to exercise after adenosine receptor and K⁺_ATP channel blockade is dependent on endogenous NO. Dogs were studied at rest and during a four-stage treadmill exercise protocol under control conditions, during K⁺_ATP channel blockade with glibenclamide (50 μg · kg⁻¹ · min⁻¹ IC) in the presence of adenosine receptor blockade with 8-phenyltheophylline (8-PT, 5 mg/kg IV), and after the addition of the NO synthase inhibitor N^G-nitro-l-arginine (LNNA, 1.5 mg/kg IC). During control conditions, coronary blood flow was 49±3 mL/min at rest and increased to 92±8 mL/min at peak exercise. LNNA alone or in combination with 8-PT did …