Schurman Scott J, Bergstrom William H, Shoemaker Lawrence R, Welch Thomas R
Department of Pediatrics, Division of Nephrology, Upstate Medical University, 750 E. Adams Street, Syracuse, NY 13210, USA.
Pediatr Nephrol. 2004 Jan;19(1):33-5. doi: 10.1007/s00467-003-1361-4. Epub 2003 Nov 25.
Children with neonatal Bartter syndrome (NBS) have hypercalciuria, nephrocalcinosis, and osteopenia. A complex of basic-fibroblast growth factor (b-FGF) and a naturally occurring glycosaminoglycan has been identified in the serum and urine of NBS patients. This complex increases bone resorption in a bone disc bioassay system. Angiotensin II (AT II), which is increased in Bartter syndrome, increases the synthesis of b-FGF by cultured endothelial cells. Addition of 10(-8) M AT II to the bioassay, a concentration reported in Bartter syndrome patients, significantly decreased calcium uptake into bone discs [E/C 0.60 (0.04), P < 0.001 compared with buffer, normal E/C >0.90]. Adding b-FGF monoclonal antibody at 10 microg/ml [E/C 0.90 (0.06), P=NS] or indomethacin [E/C 1.00 (0.03), P=NS] to 10(-8 )M AT II neutralized this effect. In separate experiments, newborn rats were given intraperitoneal injections of AT II. Bone discs from these animals were used in the bioassay system and calcium uptake was markedly reduced compared with discs from rats injected with phosphate-buffered saline [AT II 6.6 x 10(-9), E/C 0.10 (0.04), P<0.001, AT II 3.3 x 10(-8), E/C 0.10 (0.05), P<0.001]. AT II decreases calcium uptake in the bone disc bioassay system. This effect can be abrogated by antibody to b-FGF or prostaglandin synthetase inhibition. These results support the hypothesis that in children with NBS, elevated levels of AT II stimulate local skeletal b-FGF synthesis, with a resultant increase in bone resorption via a prostaglandin-dependent pathway.
患有新生儿巴特综合征（NBS）的儿童会出现高钙尿症、肾钙质沉着症和骨质减少。在NBS患者的血清和尿液中已鉴定出碱性成纤维细胞生长因子（b-FGF）与一种天然存在的糖胺聚糖的复合物。在骨盘生物测定系统中，这种复合物会增加骨吸收。巴特综合征中升高的血管紧张素II（AT II）可增加培养的内皮细胞中b-FGF的合成。在生物测定中加入10(-8) M的AT II（这是巴特综合征患者中报告的浓度），与缓冲液相比，骨盘中的钙摄取量显著降低[E/C 0.60 (0.04)，与缓冲液相比P < 0.001，正常E/C > 0.90]。向10(-8) M的AT II中加入10微克/毫升的b-FGF单克隆抗体[E/C 0.90 (0.06)，P = 无显著性差异]或吲哚美辛[E/C 1.00 (0.03)，P = 无显著性差异]可中和这种作用。在单独的实验中，给新生大鼠腹腔注射AT II。将这些动物的骨盘用于生物测定系统，与注射磷酸盐缓冲盐水的大鼠的骨盘相比，钙摄取量明显降低[AT II 6.6 x 10(-9)，E/C 0.10 (0.04)，P < 0.001，AT II 3.3 x 10(-8)，E/C 0.10 (0.05)，P < 0.001]。AT II会降低骨盘生物测定系统中的钙摄取。b-FGF抗体或前列腺素合成酶抑制可消除这种作用。这些结果支持这样的假说，即在患有NBS的儿童中，升高的AT II水平刺激局部骨骼b-FGF合成，进而通过前列腺素依赖性途径导致骨吸收增加。
