Renal beta2-adrenoceptor blockade worsens the outcome of an induced Escherichia coli renal infection.
BACKGROUND
Renal infections elevate the risk of sepsis and are important causes of septic shock and multiple organ failure. The objective of the present study was to test the hypothesis that renal beta(2)-adrenoceptor (beta(2)-AR) blockade impairs the organ response to renal infection induced by Escherichia coli (E. coli) administration.


METHODS
A rat model of renal infection was induced using an intraparenchymal injection of E. coli into the right kidney, either alone or in rats pre-treated with the beta(2)-AR antagonist, ICI 118,551 (3.14 microg/kg).


RESULTS
The rat renal infection model significantly raised growth-related oncogene/keratinocyte-derived cytokine, granulocyte-macrophage colony-stimulating factor and cAMP levels in the right kidney and caused an elevation in serum cytokines and nitric oxide (NO), whereas creatinine clearance rate (Ccr) was maintained over the course of the infection. Conversely, treatment of the rat model with the beta(2)-AR antagonist resulted in a decrease of Ccr and serum NO, greater increases in serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6, associated with an elevation of the right renal TNF-alpha and cannabinoid-1 receptor, and a reduction of the right renal Gsalpha and cAMP levels. Moreover, the inhibition of beta(2)-AR activation impaired the clearance of endotoxins from the kidney and was associated with a raised mortality rate.


CONCLUSIONS
The blockade of a renal beta(2)-AR signaling cascade aggravates inflammatory responses in the infected kidney, changes serum levels of cytokines, NO, and noradrenaline, and leads to renal dysfunction and a higher rate of mortality.
Nakamura
Akio
A
Department of Pediatrics, Teikyo University School of Medicine, Itabashi-ku, Tokyo - Japan. ako@med.teikyo-u.ac.jp
Niimi
Ryo
R
Yanagawa
Yukishige
Y
D058672:Adrenergic beta-2 Receptor Antagonists; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D016207:Cytokines / Q000097:blood; D004927:Escherichia coli Infections / Q000276:immunology* / Q000378:metabolism; D007674:Kidney Diseases / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D058672:Adrenergic beta-2 Receptor Antagonists; D016207:Cytokines; D009569:Nitric Oxide; D000242:Cyclic AMP; D009638:Norepinephrine