Perivascular innervation is lost in experimental atherosclerosis.

Nerve fibers, immunohistochemically positive for neuropeptide Y, tyrosine hydroxylase, calcitonin gene-related peptide and substance P, form a perivascular network surrounding the carotid arteries of New Zealand White rabbits. Transmission electron microscopy demonstrates that the nerve fibers are primarily located at the adventitial-medial border. Placing a silastic collar around a carotid artery for 14 days, in rabbits fed a diet high in cholesterol, resulted in a focal, intimal thickening in 10 out of 12 rabbits. Contralateral sham-operated arteries showed no intimal thickening. At sites where intimal thickening occurred, there was a disappearance of the perivascular nerve network. The carotid arteries from rabbits that did not respond to the collar and the sham-operated carotid arteries showed an intact and normal perivascular nerve network. In the group of animals which responded to the collar with intimal thickening, there was evidence of a proliferative response proximal to the collar and in this same tissue there was evidence of degeneration of nerve fibers. In conclusion, it has been demonstrated for the first time that, in regions of the carotid artery where intimal thickening occurred, there was an associated degeneration of the perivascular nerve network. The cause of this degeneration and its functional consequences require further investigation.