The effect of stunning on endothelium-dependent responses of resistance vessels in vivo remains of interest. We utilized the coronary pressure-flow relationship during maximal vasodilation in anesthetized swine to identify subtle changes in flow reserve within stunned myocardium. Prior to and following stunning, the coronary pressure-flow relationship during maximal doses of intracoronary adenosine was compared with that of the endothelium-dependent vasodilator ATP. In 11 anesthetized swine, 30 min of partial LAD occlusion and 40 min of reperfusion reduced fractional shortening from 16 +/- 4% to 6 +/- 5% (p < 0.05). This caused a rightward shift of the coronary pressure-flow relationships during infusions of either adenosine or ATP, suggestive of increased extra vascular compressive forces. With adenosine, the slope of the linear portion of the relationship (i.e., coronary pressures > 30 mmHg) was 1.31 +/- 0.54 ml/min-mmHg at baseline and 1.30 +/- 0.55 ml/min-mmHg following stunning (NS). With ATP however, the slope decreased from 1.34 +/- 0.48 ml/min-mmHg at baseline to 1.08 +/- 0.47 ml/min-mmHg following reperfusion (p < 0.05), indicating an attenuation of endothelium-dependent vasodilator capacity. In five of the animals, the slope of the pressure-flow relationship during intracoronary nitroprusside was unchanged post-stunning, which is similar to the adenosine results. In conclusion, the data support the hypothesis that endothelium-dependent vasodilation of resistance vessels in the intact animal is altered within severely stunned myocardium. The rightward shift of the coronary pressure-flow relationships with both classes of vasodilators suggest that extra vascular factors may also play a role in limiting coronary flow reserve.