Possible Origins and Distribution of Immunoreactive Nitric Oxide Synthase-Containing Nerve Fibers in Cerebral Arteries

Abstract

The distribution of perivascular nerve fibers expressing nitric oxide synthase (NOS)-immunoreactivity was examined in Sprague-Dawley and Long-Evans rats using affinity-purified rabbit antisera raised against NOS from rat cerebellum. NOS immunoreactivity was expressed within the endothelium and adventitial nerve fibers in both rat strains. Labeled axons were abundant and dense in the proximal anterior and middle cerebral arteries, but were less numerous in the caudal circle of Willis and in small pial arteries. The sphenopalatine ganglia were the major source of positive fibers in these vessels. Sectioning postganglionic parasympathetic fibers from both sphenopalatine ganglia reduced the density of NOS-immunoreactive (IR) nerve fibers by > 75% in the rostral circle of Willis. Moreover, NOS-IR was present in 70-80% of sphenopalatine ganglion cells. Twenty percent of these neurons also contained vasoactive intestinal polypeptide (VIP)-immunoreactivity. By contrast, the superior cervical ganglia did not contain NOS-IR cells. In the trigeminal ganglion, NO-IR neurons were found chiefly within the ophthalmic division; approximately 10-15% of neurons were positively labeled. Colocalization with calcitonin gene-related peptide (CGRP) was not observed. Sectioning the major trigeminal branch innervating the circle of Willis decreased positive fibers by < or = 25% in the ipsilateral vessels. In the nodose ganglion, 20-30% of neurons contained NOS-immunoreactivity, whereas less than 1% were in the C2 and C3 dorsal root ganglia. Three human circles of Willis obtained at autopsy showed sparse immunoreactive fibers, chiefly within vessels of the posterior circulation. Postmortem delay accounted for some of the reduced density. Our findings indicate that nerve fibers innervating cerebral arteries may serve as a nonendothelial source of the vasodilator nitric oxide (NO). The coexistence of NOS and VIP within sphenopalatine ganglion cells raises the possibility that two vasodilatory agents, one, a highly diffusable short-lived, low-molecular-weight molecule, and the other, a polar 28 amino acid-containing peptide, may serve as coneuromediators within the cerebral circulation.

Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: A review of experimental studies

“…Therefore, NO, a basic mediator of vasodilation, is likely to be involved in cSCS-induced cerebral vasodilation. However this study did not determine whether NO synthase was from endothelial NOS, or the neuronal NOS that likely comes from nonadrenergic-noncholinergic nerve fibers (Nozaki et al, 1993). CGRP is another vasodilator that potentially contributes to cerebral vasodilation produced by cSCS in the same way that it contributes to SCS-induced vasodilation in the limbs .…”

Neuronal nitric oxide mediates cerebral vasodilatation during acute hypertension

“…There has been little evidence to show how the nitroxidergic parasympathetic influence on cerebral blood vessels may participate in physiological processes in the whole animal although its having been found in so many vertebrate species (Goadsby, P. J. et al, 1996;Kimura, T. et al, 1997;Nozaki, K. et al, 1993;Toda, N. et al, 2000b;Yu, J. G. et al, 1997) certainly suggests that it might serve an important role. In fact, some reports have suggested both pathophysiologic as well as physiologic involvement of the pathway.…”

Nitrergic nerves derived from the pterygopalatine ganglion innervate arteries irrigating the cerebrum but not the cerebellum and brain stem in monkeys

“…1,2 Histochemistry has showed that nitric oxide synthase (NOS)-containing nerves originating from the pterygoparatine ganglion (PPG) innervate arteries irrigating the cerebrum in many species. [3][4][5][6] We have reported that electrical stimulation of the unilateral PPG or the greater petrosal nerve (GPN), a preganglionic parasympathetic nerve that synaptically connects to the PPG, dilates the ipsilateral anterior cerebral artery (ACA), and the middle cerebral artery (MCA) in anesthetized monkeys 7 and dogs. 8 We have also found that these dilatations are suppressed by a NOS inhibitor.…”