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
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
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.
The results suggest differences in the endothelial control of the coronary circulation by endothelium-dependent substances in humans.
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