Effect of vasoactive intestinal peptide and the distribution of receptors in human epicardial coronary arteries

Abstract

Background The aim of this study was to elucidate a possible role for vasoactive intestinal peptide (VIP) in the regulation of coronary vascular tone. Its action and the distribution of [125I]-VIP binding sites were examined in isolated human coronary arteries. Methods A total of 97 segments were obtained from 23 patients undergoing cardiac transplantation. Results VIP (10−10 to 3 × 10−7 M) relaxed preconstricted coronary segments in a concentration-dependent manner, with a maximum response of 73.8% ± 8.5% of the maximum relaxation induced by 1 μg/mL of nitroglycerin. This action was inhibited by the specific receptor antagonist [4CI-D-Phe6, Leu17] VIP, with a reduction of the maximum effect from 73.8% ± 8.5% to 38.9% ± 5.4% (P < 0.001). Prior exposure to atropine and indomethacin, and removal of the endothelium had no effect on responses to VIP. Receptor autoradiography demonstrated that [125I]-VIP binding sites were displaced by unlabeled peptide and by [4CI-D-Phe6, Leu17] VIP in a concentration-dependent manner, with 50% inhibitory concentration values of 1.35 × 10−8 and 2.41 × 10−8 M, respectively. The binding was predominantly associated with smooth muscle and perivascular regions, with no binding to the endothelial cells. Conclusions Our results indicate that VIP elicits vasodilatation of the human coronary artery by acting mainly on specific receptors presumably present on the smooth muscle. This peptidergic control mechanism may play a role in the regulation of coronary artery tone.