title: Angiotensin II type 2 receptors facilitate reinnervation of phenol-lesioned vascular calcitonin gene-related peptide-containing nerves in rat mesenteric arteries.
abstract: The present study was designed to investigate involvement of angiotensin II (Ang II) type 2 receptors (AT2 receptors) in restoration of perivascular nerve innervation injured by topical phenol treatment. Male Wistar rats underwent in vivo topical application of 10% phenol around the superior mesenteric artery. After phenol treatment, animals were subjected to immunohistochemistry of the third branch of small arteries, Western blot analysis of AT2 receptor protein expression in dorsal root ganglia (DRG) and studies of mesenteric neurogenic vasoresponsiveness. Ang II (750 ng/kg/day), nerve growth factor (NGF; 20 microg/kg/day) and PD123,319 (AT2 receptor antagonist; 10 mg/kg/day) were intraperitoneally administered for 7 days using osmotic mini-pumps immediately after topical phenol treatment. Losartan (AT1 receptor antagonist) was administered in drinking water (0.025%). Phenol treatment markedly reduced densities of both calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and neuropeptide Y (NPY)-LI-containing fibers. NGF restored densities of both nerve fibers to the sham control level. Coadministration of Ang II and losartan significantly increased the density of CGRP-LI-fibers but not NPY-LI-fibers compared with saline control. The increase of the density of CGRP-LI-fibers by coadministration of Ang II and losartan was suppressed by adding PD123,319. Coadministration of Ang II and losartan ameliorated reduction of CGRP nerve-mediated vasodilation of perfused mesenteric arteries caused by phenol treatment. The AT2 receptor protein expression detected in DRG was markedly increased by NGF. These results suggest that selective stimulation of AT2 receptors by Ang II facilitates reinnervation of mesenteric perivascular CGRP-containing nerves injured by topical phenol application in the rat.
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hobara
authors.forename: M
authors.initials: M
authors.lastname: Goda
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Takatori
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
authors.forename: M
authors.initials: M
authors.lastname: Mio
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D017615:Enteric Nervous System / Q000166:cytology / Q000502:physiology*; D005727:Ganglia, Spinal / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D017538:Mesenteric Artery, Superior / Q000294:innervation* / Q000378:metabolism; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D019800:Phenol; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D012597:Sclerosing Solutions; D014655:Vascular Resistance / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D009478:Neuropeptide Y; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D012597:Sclerosing Solutions; D014662:Vasoconstrictor Agents; C073402:PD 123319; D019800:Phenol; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide; D019808:Losartan; D009638:Norepinephrine