The presence of a vasodilator in the cerebral blood vessels of several species is well established. The cholinergic nerve was the first nerve suggested to be the vasodilator nerve. Results from pharmacological studies, however, suggest that the transmitter for cerebral vasodilation is noradrenergic, noncholinergic (NANC) in nature. It has been hypothesized that this vasodilator transmitter is colocalized and coreleased with acetylcholine (ACh). Several vasodilating neural peptides such as vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and peptide histidine isoleucine (PHI) which are present in cerebral arteries have been considered the candidates for NANC vasodilator transmitters. These peptides induced by electrical nerve stimulation, however, is associated predominantly with an increase in cyclic GMP synthesis in the smooth muscle cells. These findings questions the hypothesis that cerebral NANC neurogenic vasodilation is mediated by these peptides. Recently, immunohistochemical studies have demonstrated that cerebral arteries receive dense nitric oxide synthase- immunoreactive (NOS-I) fibers. NOS catalyzes the conversion of L- arginine to nitric oxide (NO). Results from pharmacological studies further indicate that NO or a NO-releasing substance, which increases vascular cyclic GMP synthesis, mediates a major component of cerebral NANC neurogenic vasodilation. These morphopharmacological studies demonstrate the presence of an authentic NOergic vasodilator innervation in the cerebral circulation. The origin and exact pathways of NOergic nerve fibers, however, have to been determined. The relationship between NOergic nerves and the cholinergic neurons and that between NOergic nerves and various peptidergic neurons in cerebral blood vessels have not been elucidated either. The proposed study is designed to examine the origin and distribution pattern of NOergic nerve fibers and their relationships with other autonomic neurons in cerebral blood vessels of the cat, rat and pig. The techniques of single and double-labelling immunocytochemistry at light and ultrastructural levels will be utilized to provide a comprehensive approach to the problem. We plan to examine: (1) the innervation patter of NOS-I fibers in whole mount and cross sectioned cerebral arteries and veins of different brain regions; (2) whether sphenopalatine ganglion, the otic ganglion and/or the ciliary ganglion; and (3) whether NOS is colocalized with cholineacetyltransferase (ChAT), VIP and CGRP in the respective cholinergic, VIPergic and CGRPergic nerve fibers and ganglionic cells. Results of these anatomical and morphological studies will provide fundamental information for establishing a potential functional role for this newly discovered NOergic vasodilator innervation in the cerebral circulation. This study is a step toward our long-term goal to attempt to define the neurogenic control of brain circulation in health and disease.
