PEPTIDERGIC INNERVATION OF HUMAN EPICARDIAL CORONARY-ARTERIES

The peptidergic innervation of proximal (internal diameter, >0.8 mm) a nd distal (internal diameter, <0.8 mm) regions of human epicardial cor onary arteries was investigated by means of immunohistochemical, chrom atographic, radioimmunological, and in vitro pharmacological technique s. The use of an antiserum to the general neuronal marker protein gene product 9.5 revealed that the proximal part of epicardial arteries po ssessed a relatively sparse supply of nerve fibers forming a loose net work in the adventitia. The perivascular network increased in density as the vessels were followed distally. In both proximal and distal reg ions, the majority of nerve fibers possessed neuropeptide Y and tyrosi ne hydroxylase immunoreactivity. Calcitonin gene-related peptide (CGRP )- and substance P-immunoreactive nerve fibers were very sparse in the proximal region of the arteries and increased in number distally. Onl y a few scattered vasoactive intestinal peptide (VIP)-immunoreactive n erve fibers were detected in both arterial regions. The use of high-pe rformance liquid chromatography and radioimmunoassay revealed that the immunoreactive material present in coronary artery extracts closely r esembled synthetic peptides. An in vitro pharmacological method demons trated that neuropeptide Y elicited no detectable response in either p roximal or distal arterial segments. In contrast, CGRP, substance P, a nd VIP all produced a concentration-dependent relaxation of both arter ial regions. CGRP and substance P were stronger and more potent than V IP. CGRP and substance P induced a more potent response in distal comp ared with proximal regions of the arteries. These results suggest that the peptidergic nerves supplying human large epicardial coronary arte ries may be predominantly involved in mediating vasodilation.