To investigate whether atherosclerosis and its risk factors (RF) that are known to result in abnormal coronary vasodilator responses to muscarinic receptor stimulation with acetylcholine(ACH), are also associated with generalized endothelial receptor dysfunction, we compared the effects of substance P (SP) with those of ACH in the human coronary vasculature. In 25 patients, 7 (Group 1) with normal coronary arteries and no RF, and 18 (Group 2) with either RF for, orestablished atherosclerosis (>20% stenosis), intracoronary ACH (3, 30, 100, 300μg/min) and SP (5, 10, 20pmol/min) were given. Coronary blood flow was measured using a Doppler flow wire and epicardial coronary artery (ECA) diameter by quantitative angiography.