Renal Effects of β2-Adrenoceptor Agonist and the Clinical Analysis in Children

The objectives of the present study were to define the contribution of β2-adrenoceptors(β2-ARs) agonists to renal physiology and to investigate whether over-expression of renal β2-ARs might be implicated in the pathogenesis of renal dysfunction in children as an adverse effect of β2-AR activation. The renal functional responses to the systemic injection of the β2-AR agonist terbutaline in Wistar rats over-expressing renal β2-AR were compared with those of nontreated rats. Furthermore, we evaluated intrarenal β2-AR expression in 34 children (age 2–15 y) and the changes in serum creatinine levels of 99 children (age 1–15 y) who received β2-AR agonists. The animal study showed that the suppression of glomerular function by terbutaline was associated with a reduction in systemic blood pressure and over-expression of renal β2-ARs. Moreover, in rats over-expressing renal β2-ARs, administration of terbutaline resulted in a high mortality rate after a lipopolysaccharide challenge. The clinical study showed that renal β2-AR expression gradually increased with age and was up-regulated by steroid therapy. These findings indicate that the renal dysfunction caused by β2-AR agonists can be explained, at least partly, by enhanced β2-AR expression in the kidney. This may have important implications for the use of β2-AR agonists in the treatment of sick children with, for example, steroid therapy or endotoxemia.