Role of bradykinin B2 receptors in neonatal kidney growth.

The kallikrein-kinin system is developmentally expressed in newborn kidneys. In addition, bradykinin (BK) is mitogenic in cultured glomerular mesangial cells. However, the role of endogenous BK in postnatal renal development has not been defined. In this study, the role of the BK-B2 receptor in neonatal kidney growth in the rat was examined. RNA blot analysis and semiquantitative reverse transcription-polymerase chain reaction showed that BK-B2 mRNA levels were approximately 30- to 40-fold higher in newborn than adult kidneys. Treatment of newborn rats with the selective BK-B2 antagonist, Hoe 140 (600 micrograms/kg per day, sc), from days 1 through 14 of life significantly reduced body weight, kidney-to-body weight ratios, and kidney DNA content, compared with saline-treated controls. Hoe 140 treatment had no effect on kidney protein or RNA content or the expression of transforming growth factor-beta mRNA. The growth retardation induced by BK-B2 blockade was observed only in the kidney and, to a lesser extent, in the heart. BK-B2 blockade had no effect on renal growth in adult rats, suggesting that these effects are developmentally regulated. In contrast to Hoe 140 treatment, neonatal protein undernutrition resulted in a generalized reduction in kidney DNA, RNA, and protein contents; increased renal transforming growth factor-beta gene expression; and decreased renal kallikrein expression and enzymatic activity. The results suggest that activation of BK-B2 receptor expression in the neonatal kidney plays an important role in the regulation of DNA synthesis during the latter stages of nephrogenesis.