Neurotrophic Effect of Hepatic Growth Factor (HGF) on Reinnervation of Perivascular Calcitonin Gene-Related Peptide (CGRP)-Containing Nerves Following Phenol-Induced Nerve Injury in the Rat Mesenteric Artery

Abstract

Hepatic growth factor (HGF) has neurotrophic effects in the motor neurons and central nervous system. However, there has been no report about the neurotrophic action on perivascular nerves innervating the resistance artery. We investigated whether HGF can restore innervation or function of perivascular nerves, including neuropeptide Y (NPY)-containing sympathetic adrenergic nerves and calcitonin gene-related peptide (CGRP)-containing nerves, in rat mesenteric artery. To investigate HGF-mediated neurotrophic effects, Wistar rats under pentobarbital-Na anesthesia underwent in vivo perivascular denervation by topical application of phenol on the superior mesenteric artery, and then HGF or nerve growth factor (NGF) was administered for 7 days using an osmotic mini-pump after phenol-treatment. HGF significantly increased the density and number of CGRP-like immunoreactivity (LI)–containing nerve fibers compared with saline administration, while HGF did not affect the density of NPY-containing adrenergic nerve fibers. After 7-day treatment with HGF and phenol, the vascular response of vasodilation was recovered from nerve injury by phenol treatment, but vasoconstriction was not. HGF and NGF induced neurite outgrowth in rat cultured dorsal root ganglia (DRG). These results suggest that HGF has a specific neurotrophic action on reinnervation of vascular CGRP-LI–containing nerve fibers in the rat mesenteric artery and DRG.