Renal β2-adrenoceptor blockade worsens the outcome of an induced Escherichia coli renal infection

Abstract 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 β2-adrenoceptor (β2-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 β2-AR antagonist, ICI 118,551 (3.14 µg/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 β2-AR antagonist resulted in a decrease of Ccr and serum NO, greater increases in serum tumornecrosis factor-α (TNF-α) and interleukin-6, associated with an elevation of the right renal TNF-α and cannabinoid-1 receptor, and a reduction of the right renal Gsα and cAMP levels. Moreover, the inhibition of β2-AR activation impaired the clearance of endotoxins from the kidney and was associated with a raised mortality rate. Conclusion: The blockade of a renal β2-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.