Renal beta(2)-adrenoceptor modulates the lipopolysaccharide transport system in sepsis-induced acute renal failure.
The aim of this study was to define the contribution of renal beta(2)-adrenoceptor (beta(2)-AR) system to regulation of the lipopolysaccharide (LPS) transport system in the kidney of endotoxin-induced septic rats. Seven-week-old Wistar rats (n = 6/groups) pre-treated with the beta(2)-AR antagonist (ICI118,551: 3.14 microg/kg) or saline were injected with LPS (10 mg/kg i.p.) or saline, and then 24 hours later, renal function, beta(2)-AR signaling proteins, innate immune proteins, and cytokines were assayed. The injection of LPS depressed creatinine clearance rate (Ccr) associated with the reduction of renal Gsalpha and cAMP levels by a single dose of ICI118,551. On the other hand, renal CD14, toll-like receptor 4(TLR4), and tumour necrosis factor (TNF)-alpha protein expressions were significantly increased (P < 0.05) by the combination of LPS and ICI118,551. The reduction of Ccr by LPS plus ICI118,551 suggests a possibility that renal specific up-regulation of the CD14-TLR4-TNF-alpha signaling cascade by beta(2)-AR inhibition might be involved in sepsis-induced ARF.
Nakamura
Akio
A
Department of Pediatrics, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo, Japan. akio@med.teikyo-u.ac.jp
Niimi
Ryo
R
Yanagawa
Yukishige
Y
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D004731:Endotoxins / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D018805:Sepsis / Q000150:complications / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D004731:Endotoxins; D008070:Lipopolysaccharides; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; C026777:ICI 118551