Renal effects of beta2-adrenoceptor agonist and the clinical analysis in children

The objectives of the present study were to define the contribution of beta2-adrenoceptors (beta2-ARs) agonists to renal physiology and to investigate whether over-expression of renal beta2-ARs might be implicated in the pathogenesis of renal dysfunction in children as an adverse effect of beta2-AR activation. The renal functional responses to the systemic injection of the beta2-AR agonist terbutaline in Wistar rats over-expressing renal beta2-AR were compared with those of nontreated rats. Furthermore, we evaluated intrarenal beta2-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 beta2-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 beta2-ARs. Moreover, in rats over-expressing renal beta2-ARs, administration of terbutaline resulted in a high mortality rate after a lipopolysaccharide challenge. The clinical study showed that renal beta2-AR expression gradually increased with age and was up-regulated by steroid therapy. These findings indicate that the renal dysfunction caused by beta2-AR agonists can be explained, at least partly, by enhanced beta2-AR expression in the kidney. This may have important implications for the use of beta2-AR agonists in the treatment of sick children with, for example, steroid therapy or endotoxemia.