To determine the role of endothelium-mediated flow-dependent coronary dilatation in humans, we studied the coronary dilatation exerted by maximal pharmacologic increase of coronary flow in 14 patients with normal coronary arteries. Biplane views of the circumflex (Cx) and left anterior descending (LAD) coronary arteries were obtained before and 80 seconds after inducing a maximal increase in flow selectively in the Cx by injecting 7 mg papaverine through a 2F infusion catheter in the midportion of the Cx (n = 10). The diameter of the proximal Cx segment (exposed to increased flow but not to papaverine directly) increased with papaverine by 11.1 +/- 4% (range, 5.2-16.4%, p less than 0.001 vs. control), whereas the LAD diameter did not change. LAD and Cx diameters increased by 18.3% and 21.2% after nitroglycerin given into the left main artery, which showed the preserved capability of the LAD to dilate. In four patients with normal coronary arteries and six patients with coronary artery disease (CAD, non-flow-limiting stenosis), a similar protocol was applied with the LAD for the assessment of flow-dependent dilatation. Simultaneously, intracoronary blood flow velocity was measured by an intracoronary Doppler catheter. Papaverine-induced coronary flow reserve (peak/resting velocity ratio) in the LAD was 4 +/- 0.7 (range, 3.5-5) in normal arteries and was 3.5 +/- 0.6 (range, 2.7-4.4) in CAD.(ABSTRACT TRUNCATED AT 250 WORDS)