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J Am Soc Nephrol 15:316-325, 2004
© 2004 American Society of Nephrology

BASIC SCIENCE

{beta}2-Adrenoceptor Activation Attenuates Endotoxin-Induced Acute Renal Failure

Akio Nakamura*, Akira Imaizumi*, Yukishige Yanagawa*, Takao Kohsaka{dagger} and Edward J. Johns{ddagger}

*Department of Pediatrics, Teikyo University School of Medicine, Tokyo, Japan; {dagger}Department of Immunology, National Children’s Medical Centre, Tokyo, Japan; and {ddagger}Department of Physiology, University College Cork, Cork, Ireland.

Correspondence to: Dr. Akio Nakamura, Department of Paediatrics, Teikyo University School of Medicine, 2–11–1 Kaga, Itabashi-ku, Tokyo 173, Japan. Phone: 03-3964-1211 ext. 1480; Fax: 03-3579-8212; E-mail: akio{at}med.teikyo-u.ac.jp

ABSTRACT. Abnormalities in the {beta}2-adrenergic control of organ function have been implicated in the pathogenesis of several disease states, such as septic shock. The objectives of the present study were to define the contribution of {beta}2-adrenoceptors ({beta}2-AR) to normal renal physiology and to investigate whether overexpression of renal {beta}2-AR might be potentially beneficial in preventing progressive renal damage associated with endotoxemia. Adenoviral transgenes containing the human {beta}2-AR (Adeno-{beta}2-AR) were constructed and delivered into the rat kidney by means of intraparenchymal injections. Administration of 109 total viral particles of Adeno-{beta}2-AR induced an approximately threefold increase in {beta}2-AR density in the renal tissue, which 2 wk after delivery, enhanced GFR and sodium reabsorption compared with control rats. The enhanced GFR was abolished by the addition of the {beta}2-AR antagonist, ICI 118,551. Administration of lipopolysaccharide (LPS) caused a reduction in GFR, {beta}2-AR density, and cAMP together with enhanced TNF-{alpha} mRNA in the kidney. In rats overexpressing {beta}2-AR, the reduction in baseline GFR and elevation of TNF-{alpha} mRNA and leukocyte infiltration into the kidney associated with the endotoxin were blocked. These findings suggested the possibility that a renal-specific overexpression of {beta}2-AR preserves basal renal function in response to a ligand-independent {beta}2-AR activation and that the delivery of Adeno-{beta}2-AR gene is a potential novel therapeutic strategy for treatment of acute renal failure associated with sepsis.






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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673