Dual Adrenergic and Cholinergic Innervation of the Cerebral Arteries of the Rat

The innervation of the anterior cerebral artery of the rat was examined by electron microscopy and by the fluorescence method for localizing adrenergic nerves. Two groups of axon bundles were associated with the artery; one at the outer margin of the adventitia ( periadventitial bundles) and the other within the adventitia or at the adventitia-media border ( adventitial bundles). Periadventitial bundles consisted of nonmyelinated axons (0.1-2µ diam), some of which contained synaptic vesicles; in some bundles, myelinated axons were seen. Adventitial axons often contained many synaptic vesicles and were free of Schwann cell sheath in areas apposed to smooth muscle cells. The closest observed approach of axon to muscle cell was 800 A. No nerve fibers penetrated the medial muscle. After fixation with glutaraldehyde plus osmium, large (1000 A) granular and small (500 A) agranular vesicles were seen within many axon profiles. Small granular vesicles were rare. After permanganate fixation, terminal axons contained (besides large granular vesicles) either predominantly small granular vesicles or exclusively small agranular vesicles. Two days after sympathetic denervation, no axons containing small granular vesicles and no fluorescent fibers were seen. Adrenergic fibers were readily identified after injection of rats with 6-hydroxydopamine; small vesicles of adrenergic axons contained highly opaque granular cores, even in osmium-fixed material. Axons containing small agranular vesicles after 6-hydroxydopamine were considered cholinergic. The density of granulation of the large vesicles of adrenergic, but not cholinergic, axons was considerably enhanced following 6-hydroxydopamine. Both adrenergic and cholinergic axons come into close relationship with smooth muscle cells.