title: Dexamethasone treatment of post-MI rats attenuates sympathetic innervation of the infarct region.
abstract: Sympathetic fiber innervation of the damaged region following injury represents a conserved event of wound healing. The present study tested the hypothesis that impaired scar healing in post-myocardial infarction (post-MI) rats was associated with a reduction of sympathetic fibers innervating the infarct region. In 1-wk post-MI rats, neurofilament-M-immunoreactive fibers (1,116 +/- 250 microm(2)/mm(2)) were detected innervating the infarct region and observed in close proximity to a modest number of endothelial nitric oxide synthase-immunoreactive scar-residing vessels. Dexamethasone (Dex) treatment (6 days) of post-MI rats led to a significant reduction of scar weight (Dex + MI 38 +/- 4 mg vs. MI 63 +/- 2 mg) and a disproportionate nonsignificant decrease of scar surface area (Dex + MI 0.54 +/- 0.06 cm(2) vs. MI 0.68 +/- 0.06 cm(2)). In Dex-treated post-MI rats, the density of neurofilament-M-immunoreactive fibers (125 +/- 47 microm(2)/mm(2)) innervating the infarct region was significantly reduced and associated with a decreased expression of nerve growth factor (NGF) mRNA (Dex + MI 0.80 +/- 0.07 vs. MI 1.11 +/- 0.08; P < 0.05 vs. MI). Previous studies have demonstrated that scar myofibroblasts synthesize NGF and may represent a cellular target of Dex. The exposure of 1st passage scar myofibroblasts to Dex led to a dose-dependent suppression of [(3)H]thymidine uptake and a concomitant attenuation of NGF mRNA expression (untreated 3.47 +/- 0.35 vs. Dex treated 2.28 +/- 0.40; P < 0.05 vs. untreated). Thus the present study has demonstrated that impaired scar healing in Dex-treated post-MI rats was associated with a reduction of neurofilament-M-immunoreactive fibers innervating the infarct region. The attenuation of scar myofibroblast proliferation and NGF mRNA expression may represent underlying mechanisms contributing to the diminished neural response in the infarct region of Dex-treated post-MI rats.
authors.affiliation: Département de Physiologie, Université de Montréal, Canada.
authors.forename: Viviane
authors.initials: V
authors.lastname: El-Helou
authors.forename: Cindy
authors.initials: C
authors.lastname: Proulx
authors.forename: Hugues
authors.initials: H
authors.lastname: Gosselin
authors.forename: Robert
authors.initials: R
authors.lastname: Clement
authors.forename: Andrea
authors.initials: A
authors.lastname: Mimee
authors.forename: Louis
authors.initials: L
authors.lastname: Villeneuve
authors.forename: Angelino
authors.initials: A
authors.lastname: Calderone
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019922:GAP-43 Protein / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D020932:Nerve Growth Factor / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000305:Adrenal Cortex Hormones; D019922:GAP-43 Protein; D016900:Neurofilament Proteins; D012333:RNA, Messenger; C061195:neurofilament protein M; D003907:Dexamethasone; D020932:Nerve Growth Factor; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat