Innervation and Functional Aspects of Neuropeptides in the Coronary Circulation

Sammanfattning: A network of perivascular nerve fibres was demonstrated in coronary arteries and veins from guinea-pig and man. Nerve fibres displaying immunoreactivity to neuropeptide Y (NPY) had a distribution pattern similar to those containing immunoreactivity to tyrosine hydroxylase. Immunoreactivity to substance P and calcitonin gene-related peptide (CGRP) occurred in the same varicose nerve fibres, which were distinct from those displaying immunoreactivity to NPY, and NPY-immunoreactive nerve fibres were distinct from those displaying acetylcholinesterase activity. Only few nerve fibres positive for vasoactive intestinal peptide (VIP) were detected. Immunoreactivity to endothelin was demonstrated over the endothelium, and mRNA encoding the endothelin-A (ET-A) and the endothelin-B (ET-B) receptor were detected in human epicardial coronary arteries with and without endothelium and in human coronary veins. Vasomotor responses to different vasoactive substances were tested on isolated coronary vessels. Noradrenaline (NA) and adenosine 5'-triphosphate (ATP) induced mainly contraction of human epicardial coronary veins, whereas relaxant responses were more pronounced in human epicardial coronary arteries. Coronary arteries from older individuals were however more susceptible to NA-mediated contraction than those from younger persons. Relaxation of human epicardial coronary arteries induced by NA, isoprenaline and ATP were endothelium-independent. NPY had no direct vasomotor effect on human epicardial coronary arteries and veins, but in guinea-pig epicardial coronary arteries NPY inhibited relaxant responses induced by acetylcholine (ACh), VIP, substance P and isoprenaline. ACh induced strong contraction of human epicardial coronary arteries and veins, and at lower concentrations ACh induced endothelium-dependent relaxation of human epicardial coronary arteries. Substance P, CGRP and VIP potently relaxed coronary arteries and veins. In human epicardial coronary arteries, the relaxation to substance P was endothelium-dependent whereas the relaxation to CGRP seemed to be partially endothelium-dependent, and relaxation to VIP independent of an intact endothelium. Studies with different agonists and antagonists to ET-A and ET-B receptors suggested that contractions are mediated by the ET-A receptor and relaxations mediated by the ET-B receptor. The ET-B receptor mediated relaxation of human epicardial coronary arteries was endothelium-dependent.