title: Landiolol, an ultrashort-acting beta1-adrenoceptor antagonist, has protective effects in an LPS-induced systemic inflammation model.
abstract: Previous studies suggest that the blockade of beta-adrenoceptors augments the release of inflammatory regulators in response to proinflammatory stimuli. High-mobility group box 1 (HMGB-1) is a key mediator in the development of sepsis. We investigated whether landiolol, a short-acting selective beta1-adrenoceptor-blocking agent, can attenuate acute lung injury and cardiac dysfunction in a rat model of endotoxin-induced sepsis. We administered LPS i.v. to rats, with or without simultaneous treatment with landiolol (0.1 mg/kg per min). After the induction of sepsis by LPS treatment, we measured cytokine and HMGB-1 levels in the serum and lung tissue. In addition, we performed histopathology, determined wet-to-dry weight ratios, and measured cardiac function and cell signaling in the lung. Cotreatment with landiolol was associated with significantly less severe disease, as assessed by lung histopathology and cardiac function metrics. Serum and lung HMGB-1 levels were lower over time among landiolol-treated animals. Furthermore, nuclear factor-kappaB activity was inhibited by the administration of landiolol. Cotreatment with the selective beta1-adrenoceptor-blocking agent landiolol protects against acute lung injury and cardiac dysfunction in a rat model of LPS-induced systemic inflammation. Treatment was associated with a significant reduction in serum levels of the inflammation mediator HMGB-1 and histological lung damage.
authors.affiliation: Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, Yufu City, Oita, Japan. saku@med.oita-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Hayato
authors.initials: H
authors.lastname: Maeda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009025:Morpholines; D014409:Tumor Necrosis Factor-alpha; C077049:landiolol; D014508:Urea