PEPTIDERGIC INNERVATION OF GUINEA-PIG BRAIN VESSELS - COMPARISON WITHIMMUNOHISTOCHEMISTRY AND IN-VITRO PHARMACOLOGY IN ROSTRALLY AND CAUDALLY LOCATED ARTERIES

The peptidergic innervation of the guinea-pig basilar artery and the p osterior, middle and anterior cerebral arteries were studied by means of immunohistochemical and image analysis techniques using whole mount preparations. An in vitro pharmacological study was performed to corr elate the distribution of peptide-containing nerves and the action of neuropeptides on vessel segments from the same vascular regions, The o verall distribution of perivascular nerve fibres was demonstrated usin g an antiserum to the general neuronal marker protein gene product 9.5 (PGP 9.5) and the percentage immunostained area of total vessel wall area occupied by PGP-containing nerves, in each of the basilar, poster ior and middle cerebral arteries, was set at 100% and used to determin e the relative density of specific populations of autonomic and sensor y nerve fibres. In all four cerebral arteries, the majority of nerve f ibres possessed neuropeptide Y (NPY) and tyrosine hydroxylase (TH) imm unoreactivity, occupying 6.2-13.3% and 5.8-7.5% of the total vessel wa ll area, respectively. Vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin-gene-related peptide (CGRP) were detected at low er densities. The pharmacological study performed on small circular se gments with an intact endothelium revealed that, in all four cerebral arteries, NPY was a more potent constrictor than noradrenaline (NA), T he rank order of potency for relaxant agents was CGRP = SP. VIP > ACh in the PCA and MCA, and SP = CGRP > VIP > ACh in the BA and ACA, The c orrelation between immunostained nerve area and the agonist potency su ggested that the denser the peptidergic nerve-supply, the lower the se nsitivity to the agonist.