EFFECTS OF INHIBITION OF NITRIC-OXIDE FORMATION ON THE REGULATION OF CORONARY BLOOD-FLOW IN ANESTHETIZED DOGS

In 11 open-chest dogs with a flowmeter on the left circumflex artery, L-NMMA, a selective inhibitor of nitric oxide-formation, was subselect ively infused into the left circumflex artery at a rate of 2.5 mg/ml ( ml/min) to avoid systemic hemodynamic effects. The coronary blood flow at normal arterial blood pressure was similar prior to and during L-N MMA infusion. However, when the arterial blood pressure was raised by inflating a balloon in the descending aorta, the nitric oxide suppress ion induced a dramatic increase in coronary vascular resistance by alm ost 40 % compared to control conditions without L-NMMA infusion at ide ntically elevated arterial blood pressure. L-NMMA induced a significan t downward shift and flattening of the pressure-flow relation over a p ressure range from 60 - 150 mmHg. Peak hyperemic coronary now after 20 -s transient coronary occlusion was similar prior to and during L-NMMA infusion, but the duration of the hyperemic flow response was signifi cantly shortened during L-NMMA infusion indicating exaggerated constri ction after hyperemic stimulus. The EDRF/nitric oxide-system plays an important role for the regulation of coronary blood flow by counteract ing autoregulatory constrictor responses to increased driving pressure and shear stress in the intact canine circulation.