Nicotine facilitates reinnervation of phenol-injured perivascular adrenergic nerves in the rat mesenteric resistance artery

作者：Takatori Shingo^*; Fujiwara Hidetoshi; Hagimori Kenta; Hashikawa Hobara Narumi; Yokomizo Ayako; Takayama Fusako; Tangsucharit Panot; Ono Nobufumi; Kawasaki Hiromu

来源：European Journal of Pharmacology, 2015, 748: 1-9.

DOI：10.1016/j.ejphar.2014.12.005

• Nicotine
• Tyrosine hydroxylase-containing adrenergic nerves
• Nerve growth factor
• alpha 7 Nicotinic acetylcholine receptor
• Rat mesenteric artery

Nicotine has been shown to have neuroprotective and neurotrophic actions in the central nervous system. To elucidate the peripheral neurotrophic effects of nicotine, we determined whether nicotine affected the reinnervation of mesenteric perivascular nerves following a topical phenol treatment. A topical phenol treatment was applied to the superior mesenteric artery proximal to the abdominal aorta in Wistar rats. We examined the immunohistochemistry of the distal small arteries 7 days after the treatment. The topical phenol treatment markedly reduced the density of tyrosine hydroxylase (TH)-LI and calcitonin gene-related peptide (CGRP)-LI fibers in these arteries. The administration of nicotine at a dose of 3 mg/kg/day (1.5 mg/kg/injection, twice a clay), but not once a day or its continuous infusion using a mini-pump significantly increased the density of TH-LI nerves without affecting CGRP-Ll nerves. A pretreatment with nicotinic acetylcholine receptor antagonists hexamethonium, mecamylamine, and methyllycaconitine, but not dextrometorphan, canceled the TH-LI nerve reinnervation induced by nicotine. Nicotine significantly increased NGF levels in the superior cervical ganglia (SCG) and mesenteric arteries, but not in the dorsal root ganglia, and also up-regulated the expression of NGF receptors (TrkA) in the SCG, which were canceled by hexamethonium. These results suggested that nicotine exhibited neurotrophic effects that facilitated the reinnervation of adrenergic TH-LI nerves by activating alpha 7 nicotinic acetylcholine receptor and NGF in the SCG.

• 出版日期2015-2-5