title: Significant reversal of cardiac upregulated endothelin-1 system in a rat model of sepsis by landiolol hydrochloride.
abstract: OBJECTIVE
  Landiolol hydrochloride, an ultra-short-acting highly cardio-selective β-1 blocker, has become useful for various medical problems. Recent studies have demonstrated that co-treatment with landiolol protects against acute lung injury and cardiac dysfunction in rats of lipopolysaccharide (LPS)-induced systemic inflammation, and was also associated with a significant reduction in serum levels of the inflammation mediator HMGB-1 and histological lung damage. Endothelin (ET)-1, a potent vasoconstrictor, has been implicated in pathogenesis of sepsis and sepsis-induced multiple organ dysfunction syndrome. Here, we investigated whether landiolol hydrochloride can play important roles in ameliorating LPS-induced alterations in cardiac ET system of septic rats.
  
  
  METHODS
  Eight-week-old male Wistar rats were administered LPS only for 3 h and the rest were treated with LPS as well as with landiolol non-stop for 3 h.
  
  
  RESULTS
  At 3 h after LPS (only) administration, circulatory tumor necrosis factor (TNF)-α level, blood lactate concentration and percentage of fractional shortening of heart were significantly increased. In addition, LPS induced a significant expression of various components of cardiac ET-1 system compared to control. Finally, treatment of LPS-administered rats with landiolol for 3 h normalized LPS-induced blood lactate levels and cardiac functional compensatory events, without altering levels of plasma TNF-α and ET-1. Most strikingly, landiolol treatment significantly normalized various components of cardiac ET-1 signaling system in septic rat.
  
  
  CONCLUSIONS
  Taken together, these data led us to conclude that landiolol may be cardio-protective in septic rats by normalizing the expression of cardiac vasoactive peptide such as ET, without altering the circulatory levels of inflammatory cytokines.
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Seki
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Subrina
authors.initials: S
authors.lastname: Jesmin
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Nobutake
authors.initials: N
authors.lastname: Shimojo
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Md Majedul
authors.initials: MM
authors.lastname: Islam
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Md Arifur
authors.initials: MA
authors.lastname: Rahman
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Tanzila
authors.initials: T
authors.lastname: Khatun
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sakuramoto
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Oki
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sonobe
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kamiyama
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hagiya
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawano
authors.affiliation: Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: mizutani@md.tsukuba.ac.jp.
authors.forename: Taro
authors.initials: T
authors.lastname: Mizutani
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014463:Ultrasonography; D015854:Up-Regulation / Q000187:drug effects*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D019332:Endothelin-1; D015850:Interleukin-6; D009025:Morpholines; D017466:Receptors, Endothelin; D014409:Tumor Necrosis Factor-alpha; C077049:landiolol; D014508:Urea
keywords: Endothelin; Heart; Landiolol hydrochloride; Rat model; Sepsis