930-107 Does the Abnormal Endothelial Response of the Human Coronary Vasculature in Atherosclerosis Extend Beyond the Muscarinic Receptor?

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.ResultsMicrovascular dilation measured as a decrease in coronary vascular resistance (CVR) with ACH was greater compared to SP (-49±23% vs. -24±19% respectively, p<0.01), but ECA dilation with SP was greater compared to ACH (0±14% (ACH) vs.16±17%SP, p<0.01).% change with ACH% change with SPCVRECA DiamCVRECA DiamGroup 1-65**9**-26**22**Group 2-41**,@3@-22**13**,@P<0.05**P<0.01 cf. to baseline@P<005 Group 1vs. Group 2Group 2 pts had depressed microvascular and ECA dilation with ACH compared to Group 1 pts (Table). In contrast, with SP, microvascular dilation was similar in both groups, and ECA dilation was higher in those without RF; however, the correlation between the magnitude of ECA dilation with ACH and SP was weak (r=0.21). Thus, there is a preponderance of muscarinic receptors in the microvessels, whereas SP receptors are located predominantly in human ECA. In pts with RF and atherosclerosis, ACH-induced endothelium dependent ECA and microvascular dilation is depressed, but microvascular dilation with SP appears unaffected and SP-induced ECA dilation is only mildly reduced. Therefore, atherosclerosis and its RF appearto produce non-uniform dysfunction of various endothelial cell surface receptors in the human coronary vasculature