Renal beta(2)-adrenoceptor modulates the lipopolysaccharide transport system in sepsis-induced acute renal failure

Inflammation. 2009 Feb;32(1):12-9. doi: 10.1007/s10753-008-9097-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism*
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Biological Transport
  • Endotoxins / toxicity
  • Kidney / drug effects
  • Kidney / metabolism*
  • Lipopolysaccharides / metabolism*
  • Propanolamines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-2 / physiology*
  • Sepsis / complications
  • Sepsis / metabolism*

Substances

  • Adrenergic beta-Antagonists
  • Endotoxins
  • Lipopolysaccharides
  • Propanolamines
  • Receptors, Adrenergic, beta-2
  • ICI 118551