EFFECT OF INHIBITION OF NITRIC-OXIDE FORMATION ON CORONARY BLOOD-FLOW DURING EXERCISE IN THE DOG

Objective: The aim was to test the hypothesis that nitric oxide (or a related compound) contributes to the coronary vasodilatation during physiological increases of myocardial O2 consumption that occur with exercise. Methods: Active hyperaemia associated with graded treadmill exercise and coronary reactive hyperaemia were examined in chronically instrumented awake dogs during control conditions and after administration of the nitric oxide synthase inhibitor, N-nitro-L-arginine (LNNA). Results: LNNA blunted the response to intracoronary acetylcholine, with an 80(SEM 6)% decrease in the maximum acetylcholine induced coronary vasodilatation, but did not alter the response to sodium nitroprusside. Increases of myocardial oxygen requirements during treadmill exercise were associated with progressive increases of coronary blood flow. LNNA caused a significant increase in arterial pressure at rest and during exercise, and this was associated with slightly but significantly higher myocardial oxygen consumption. Coronary blood flow during exercise was also slightly higher after LNNA, while coronary vascular resistance was unchanged. Coronary sinus PO2 was slightly but significantly lower during exercise after LNNA, indicating that coronary vasodilatation in response to the increased myocardial oxygen demands during exercise was slightly blunted by LNNA. LNNA did not alter the peak increase in blood flow during reactive hyperaemia following a 15 s coronary occlusion, but decreased the duration of the response and decreased reactive hyperaemia debt repayment from 300(56)% during control conditions to 182(36)% after LNNA (p<0.01). Conclusions: LNNA antagonised coronary vasodilatation in response to acetylcholine and blunted coronary reactive hyperaemia, but did not substantially impair the coronary vasodilatation associated with increased myocardial oxygen requirements produced by exercise. These findings fail to support an essential role for nitric oxide in coronary resistance vessel dilatation during exercise in the dog.