title: Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin receptor blockade.
abstract: OBJECTIVE
  We performed a randomized, prospective animal study to investigate whether inhibiting the renin-angiotensin system with a (pro)renin receptor blocker (PRRB) prevents acute lung injury (ALI) in a rodent model.
  
  
  METHODS
  We used Thirty-six male Sprague-Dawley rats. We administered lipopolysaccharide (LPS; 2 mg/kg) intratracheally with or without PRRB pretreatment (1 mg/kg/d).
  
  
  METHODS
  We performed bronchoalveolar lavage (BAL) and lung removal at 4 h after LPS administration and measured levels of inflammatory cytokines, high mobility group box 1 (HMGB-1) protein, and total protein in bronchoalveolar lavage fluid (BALF). Myeloperoxidase (MPO) activity was detected in lung tissue homogenates using a sensitive ELISA. We performed hematoxylin and eosin staining and immunohistochemical staining for nonproteolytically activated prorenin in the left lung.
  
  
  RESULTS
  The PRRB decreased leukocyte counts and total protein, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6, and IL-10 levels in the BALF and MPO activity in lung tissue. The PRRB reduced interstitial edema, hemorrhage, and the neutrophil count in the lung tissues. Consistent with the reduction in lung tissue damage, immunohistochemical staining showed that the PRRB decreased the amount of nonproteolytically activated prorenin.
  
  
  CONCLUSIONS
  The PRRB blocked LPS-induced inflammatory response in the lung and protected against ALI. Therefore, it is a potential therapeutic agent for preventing ALI.
authors.affiliation: 1Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ishii
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirano
authors.forename: Koichi
authors.initials: K
authors.lastname: Suda
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hagiwara
authors.forename: Taku
authors.initials: T
authors.lastname: Miyasho
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamada
authors.forename: Rieko
authors.initials: R
authors.lastname: Nakamura
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Takahashi
authors.forename: Norihito
authors.initials: N
authors.lastname: Wada
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kawakubo
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saikawa
authors.forename: Tai
authors.initials: T
authors.lastname: Omori
authors.forename: Tomoko
authors.initials: T
authors.lastname: Betsuyaku
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ichihara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004731:Endotoxins; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004731:Endotoxins; D018836:Inflammation Mediators; D010455:Peptides; D006180:Proton-Translocating ATPases; D011956:Receptors, Cell Surface; D025262:Vacuolar Proton-Translocating ATPases; C044101:endotoxin, Escherichia coli; C514240:ATP6AP2 protein, rat; D000093342:Prorenin Receptor
keywords: (pro)renin receptor blocker; acute lung injury; prorenin; renin–angiotensin system