Heterogeneous effects of the endothelium-dependent vasodilators acetylcholine and substance P on the coronary circulation of patients with angiographically normal coronary arteries

Background: Effects of local infusions of the endothelium-dependent vasodilators acetylcholine and substance P on the coronary circulation were studied in 14 patients with angiographically normal coronary arteries. Methods: Patients were allocated at random to receive either acetylcholine (1, 3, 10, and 30 μg/min; n = 7) or substance P (14, 40, and 140 ng/min; n = 7) subselectively into the left coronary artery. The coronary artery diameter was measured by quantitative angiography, and coronary blood flow (CBF) was assessed as the product of the arterial cross-sectional area and the mean CBF velocity measured by a Doppler catheter. Results: Acetylcholine at a dose of 3 μg/min increased coronary artery diameter, whereas 10 and 30 μg/min decreased diameter; substance P consistently increased coronary artery diameter. The increase in coronary artery diameter evoked by isosorbide dinitrate (2 mg) was comparable in the two groups. Both acetylcholine and substance P increased CBF in a dose-dependent manner. The percent increase in CBF induced by 30 μg/min acetylcholine (300%±44%, mean±SD) was significantly (P < 0.01) greater than that induced by 140 ng/min substance P (144%±45%). The percent increase in CBF induced by intracoronary papaverine (10 mg) was comparable in the acetylcholine-treated and the substance P- treated groups (322%±43% and 301%±39%, respectively). These findings suggest that substance P induces greater dilation of large epicardial coronary arteries than does acetylcholine, while acetylcholine produces greater dilation of resistance coronary arteries in the human coronary circulation. Conclusions: The results suggest differences in the endothelial control of the coronary circulation by endothelium-dependent substances in humans.