Characterization of Perivascular Nerve Distribution in Rat Mesenteric Small Arteries

Abstract

The distribution pattern of perivascular nerves in some branches of rat mesenteric arteries was studied. Mesenteric arteries isolated from 8-week-old Wistar rats were divided into the 1st-, 2nd-, and 3rd-order branches. The distribution of perivascular nerves in each branch was immunohistochemically evaluated using antibodies against neuropeptide Y (NPY), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP), substance P (SP), and neuronal nitric oxide synthase (nNOS). The density of NPY-, TH-, CGRP-, and SP-like immunoreactive (LI) nerves in the 2nd and 3rd branches was significantly greater than that in the 1st branch, and a negative relationship was found between nerve density and arterial diameter, except for TH-LI nerves. The density of NPY-and TH-LI nerves in all branches, which was similar, was greater than that of CGRP-(except for NPY-LI nerves in the 1st branch), SP-, or nNOS-LI nerves. Double immunostaining revealed that TH-LI nerves made contact with nNOS-LI, CGRP-LI, and SP-LI nerves and that CGRP-LI nerves made contact with TH-, NPY-, or nNOS-LI nerves, while TH-LI and CGRP-LI nerves nearly merged with NPY-LI and SP-LI nerves, respectively. These results suggest that the each branch of mesenteric arteries is densely innervated by vasoconstrictor nerves containing NPY, TH, and vasodilator CGRP nerves.They also suggest that the intense density of perivascular nerves in the 2nd and 3rd branches may contribute to maintaining vascular tone.Key words adrenergic nerve; nonadrenergic noncholinergic nerve; nerve distribution; rat mesenteric small artery Rat mesenteric arteries are innervated by perivascular nerves that play an important role in the maintenance of vascular tone and regulation of organ and tissue blood flow. With few exceptions, postganglionic adrenergic nerves constitute the most significant efferent neural pathway to blood vessels. The degree of microcirculation control exerted by adrenergic nerves depends, in part, on the distribution pattern of these nerves to the various segments comprising the microvascular network. The functional significance of microcirculation control via adrenergic nerves may vary among different organs and between different segments of the microvascular network in any given tissue. Resistance vessels, such as the mesenteric arteries, are known to be innervated by many perivascular nerves, such as sympathetic adrenergic nerves, and non-adrenergic non-cholinergic (NANC) nerves including CGRPergic nerves 1) and nitric oxide (NO) nerves. 2) Our previous studies also revealed the elimination of CGRPergic nerve function augmented adrenergic nerve-mediated vasoconstriction, and, conversely, adrenergic nerves via presynaptic norepinephrine release inhibited the neurogenic release of calcitonin generelated peptide (CGRP) from the nerve, thereby decreasing CGRPergic nerve function.3) We also previously demonstrated adrenergic and NO nerves innervating rat mesenteric arteries were involved in the modulation of adrenergic neurotransmission.2) These findings of neuro...

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