ROLE OF BRADYKININ B-2 RECEPTORS IN NEONATAL KIDNEY GROWTH

The kallikrein-kinin system is developmentally expressed in newborn ki dneys. In addition, bradykinin (BK) is mitogenic in cultured glomerula r mesangial cells. However, the role of endogenous BK in postnatal ren al development has not been defined. In this study, the role of the BK -B-2 receptor in neonatal kidney growth in the rat was examined. RNA b lot analysis and semiquantitative reverse transcription-polymerase cha in reaction showed that BK-B-2 mRNA levels were approximately 30- to 4 0-fold higher in newborn than adult kidneys, Treatment of newborn rats with the selective BK-B-2 antagonist, Hoe 140 (600 mu g/kg per day, s c), from days 1 through 14 of life significantly reduced body weight, kidney-to-body weight ratios, and kidney DNA content, compared with sa line-treated controls. Hoe 140 treatment had no effect on kidney prote in or RNA content or the expression of transforming growth factor-beta mRNA. The growth retardation induced by BK-B-2 blockade was observed only in the kidney and, to a lesser extent, in the heart. BK-B-2 block ade had no effect on renal growth in adult rats, suggesting that these effects are developmentally regulated. In contrast to Hoe 140 treatme nt, neonatal protein undernutrition resulted in a generalized reductio n in kidney DNA, RNA, and protein contents; increased renal transformi ng growth factor-beta gene expression; and decreased renal kallikrein expression and enzymatic activity. The results suggest that activation of BK-B-2 receptor expression in the neonatal kidney plays an importa nt role in the regulation of DNA synthesis during the latter stages of nephrogenesis.