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.
Nakamura
Akio
A
Department of Pediatrics, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-8605, Japan. akio@med.teikyo-u.ac.jp
Niimi
Ryo
R
Imaizumi
Akira
A
Yanagawa
Yukishige
Y
D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007223:Infant; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies
D058666:Adrenergic beta-2 Receptor Agonists; D018343:Receptors, Adrenergic, beta-2