title: Cutaneous wound healing of chronically stressed mice is improved through catecholamines blockade.
abstract: Stress impairs cutaneous wound healing; however, it is unclear how beta-adrenoceptors participates in alterations induced by stress on skin wound repair. Therefore, the aim of this study was to investigate the effects of propranolol, a non-selective beta-blocker, administration on cutaneous wound healing of chronically stressed mice. Male mice were spun at 115 rpm for 15 min every hour from three days before wounding until euthanasia. Control animals were not submitted to stress. Stressed and control animals were treated with propranolol dissolved in water; controls received only water. Propranolol administration began one day before wounding and was continued daily until euthanasia. A full-thickness excisional lesion was performed. Seven and fourteen days later, animals were killed, and lesions were formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin-eosin and immunostained against F4/80 to quantify macrophages, alpha-smooth muscle actin to quantify the myofibroblast density and proliferating cell nuclear antigen to quantify the cell proliferation. Furthermore, matrix metalloproteinases (MMP)-2 and MMP-9 activity, nitrite and hydroxyproline levels and tumor necrosis factor-alpha (TNF-alpha) expression were measured in wound. Stress and control + propranolol groups presented a delay in wound contraction, re-epithelialization, F4/80-positive macrophages, neutrophils and mast cells infiltration, cellular proliferation, angiogenesis, myofibroblastic differentiation, MMP-2 and MMP-9 activation and TNF-alpha expression, whereas an increase in the nitrite levels. Stress + propranolol group presented results similar to control group. In conclusion, stress impairs cutaneous wound healing in mice through beta1- adrenoceptors and beta2-adrenoceptors activation.
authors.affiliation: Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Romana-Souza
authors.forename: Luis Cristóvão
authors.initials: LC
authors.lastname: Porto
authors.forename: Andréa
authors.initials: A
authors.lastname: Monte-Alto-Costa
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002395:Catecholamines / Q000037:antagonists & inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004817:Epidermis / Q000187:drug effects; D006097:Granulation Tissue / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use*; D013312:Stress, Physiological; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000150:complications / Q000188:drug therapy* / Q000523:psychology
chemical_list: D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011433:Propranolol; D045726:Metalloproteases