Effects of calcitonin gene-related peptide on normal and atheromatous vessels and on resistance vessels in the coronary circulation in humans

Abstract

Background. Calcitonin gene-related peptide (CGRP) is a potent dilator of normal epicardial coronary vessels in humans, but its effects on myocardial blood flow and atheromatous coronary vessel diameter are unknown. Methods and Results. Seven patients were entered for study of the effects of CGRP on coronary blood flow and 13 for the comparison of its effects on normal and atheromatous coronary arteries. In the first seven patients, left anterior descending artery (LAD) diameter at an angiographically normal site, coronary sinus oxygen saturation (CSo2S), systemic blood pressure, and heart rate were measured during intracoronary infusion of increasing concentrations of CGRP (up to 200 ng/ml at 2 ml/min) followed by intracoronary adenosine (0.267 μg/ml at 2 ml/min) and finally intracoronary glyceryl trinitrate (GTN) (5 μg/ml at 2 ml/min). CGRP dilated the normal segment of the LAD by 22.6±8% (mean±95% confidence-interval), p<0.001, with only a small increase in CSo2S from 40.1±2.7% to 47.3±2.7%, p<0.001. Adenosine, a potent dilator of myocardial resistance vessels, caused no further increase in LAD diameter but caused a rise in CSo2S from 47.3±2.7% to 76.0±2.7%, p<0.001. GTN caused no further increase in LAD diameter. As heart rate-blood pressure product remained unchanged throughout the study, the increase of CSo2S indicated only a small increase in myocardial blood flow after CGRP infusion. In 13 patients with atheromatous coronary artery disease, the effects of intracoronary CGRP at angiographically normal sites, stenoses, angiographically normal sites immediately adjacent to stenoses, and sites of coronary artery wall irregularity were compared after intracoronary infusion of a single dose of CGRP (200 ng/ml at 2 ml/min) followed by intracoronary GTN (5 μg/ml at 2 ml/min). At these four sites, CGRP resulted in dilatation by 17.0±5.6%, 15.3±12.1% (NS), 7.6±5.4% (NS), and 15.9±7.8%, respectively. There was no significant further dilatation after GTN at any of the four sites. Conclusions. These data indicate that CGRP has little effect in humans at rest on coronary resistance vessels in nonischemic myocardium but causes marked dilatation of normal arteries and variable dilatation of atheromatous epicardial arteries.