This study was designed to assess the vasomotor response of coronary arteries to exercise and the cold pressor test, and its relationships with the endothelium-mediated dependent mechanism. Twenty-two patients were entered in the study. Group I was composed of 12 patients with a total cholesterol level < 200 mg/dl associated with angiographically smooth, normal coronary arteries. Group 2 consisted of 10 patients with both a cholesterol level > 240 mg/dl and angiographic luminal irregularities of the left anterior descending coronary artery. Coronary blood flow was assessed by a 0.018-inch tip guidewire during Doppler ultrasonography, and analysis of the coronary arterial dimension of the midportion of the left anterior descending coronary artery was performed by quantitative coronary angiography. Catecholamine concentrations were assessed at the different stages of the protocol. The rate-pressure product increased during both the cold pressure test and exercise (p < 0.001). Coronary blood flow velocity increased during the cold pressor and exercise tests by 24.5 +/- 10% and 72 +/- 42%, respectively (p < 0.001), and by 127 +/- 62% (p < 0.0001) after administration of papaverine. In group 1, the cold pressor test had a more pronounced vasodilating effect on epicardial coronary arteries (+11.2 +/- 16%) compared with group 2 (-2 +/- 9%, p < 0.05). Similarly, exercise had a vasodilating action in group 1 (11.3 +/- 15%) compared with group 2 (-1.9 +/- 8%, p < 0.05). Both responses were highly correlated (r = 0.92, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)