title: Propranolol impairs the closure of pressure ulcers in mice.
abstract: OBJECTIVE
  β-Adrenoceptors modulate acute wound healing; however, few studies have shown the effects of β-adrenoceptor blockade on chronic wounds. Therefore, this study investigated the effect of β1-/β2-adrenoceptor blockade in wound healing of pressure ulcers.
  
  
  METHODS
  Male mice were daily treated with propranolol (β1-/β2-adrenoceptor antagonist) until euthanasia. One day after the beginning of treatment, two cycles of ischemia-reperfusion by external application of two magnetic plates were performed in skin to induce pressure ulcer formation.
  
  
  RESULTS
  Propranolol administration reduced keratinocyte migration, transforming growth factor-β protein expression, re-epithelialization, and necrotic tissue loss. Neutrophil number and neutrophil elastase protein expression were increased in propranolol-treated group when compared with control group. Propranolol administration delayed macrophage mobilization and metalloproteinase-12 protein expression and reduced monocyte chemoattractant protein-1 protein expression. Myofibroblastic differentiation, angiogenesis, and wound closure were delayed in the propranolol-treated animals. Propranolol administration increased neo-epidermis thickness, reduced collagen deposition, and enhanced tenascin-C expression resulting in the formation of an immature and disorganized collagenous scar.
  
  
  CONCLUSIONS
  β1-/β2-Adrenoceptor blockade delays wound healing of ischemia-reperfusion skin injury through the impairment of the re-epithelialization and necrotic tissue loss which compromise wound inflammation, dermal reconstruction, and scar formation.
authors.affiliation: Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Thatiana L
authors.initials: TL
authors.lastname: Assis de Brito
authors.affiliation: Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Andréa
authors.initials: A
authors.lastname: Monte-Alto-Costa
authors.affiliation: Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: romanabio@yahoo.com.br.
authors.forename: Bruna
authors.initials: B
authors.lastname: Romana-Souza
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D004817:Epidermis / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D003668:Pressure Ulcer / Q000188:drug therapy* / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000188:drug therapy; D012867:Skin / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D008054:Lipid Peroxides; D011433:Propranolol; D006909:Hydroxyproline
keywords: Diaminobenzidine (PubChem CID: 7071); Formalin (PubChem CID: 712); Hematoxylin (PubChem CID: 442514); Hydrochloric acid (PubChem CID: 313); Ischemia–reperfusion injury; Ketamine (PubChem CID: 3821); Methanol (PubChem CID: 887); Polyacrylamide (PubChem CID: 6579); Pressure ulcer; Propranolol hydrochloride (PubChem CID: 62882); Skin; Sodium dodecylsulfate (PubChem CID: 3423265); Sodium hydroxide (PubChem CID: 14798); Sulfuric acid (PubChem CID: 1118); Wound healing; Xylazine (PubChem CID: 5707); Xylenol orange (PubChem CID: 16220156); β-Adrenoceptors