ICHIHARA Atsuhiro
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Peer reviewed
Title Attenuation of lipopolysaccharide-induced acute lung injury after (pro)renin receptor blockade.
Journal Formal name:Experimental lung research
Abbreviation:Exp Lung Res
ISSN code:01902148/15210499
Volume, Issue, Page 41(4),pp.199-207
Author and coauthor ISHII Kenjiro†, TAKEUCHI Hiroya, FUKUNAGA Koichi, HIRANO Yuki, SUDA Koichi, HAGIWARA Tomoko, MIYASHO Taku, YAMADA Shingo, NAKAMURA Rieko, TAKAHASHI Tsunehiro, WADA Norihito, KAWAKUBO Hirofumi, SAIKAWA Yoshiro, OMORI Tai, BETSUYAKU Tomoko, ICHIHARA Atsuhiro, KITAGAWA Yuko
Publication date 2015/05
Summary PURPOSE/AIM: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.MATERIALS: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, hemorRESULTS:rhage, 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.
DOI 10.3109/01902148.2014.993444
PMID 25844689