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Angiotensin II reduces calcium uptake into bone
Scott J Schurman1, William H Bergstrom, Lawrence R Shoemaker
1Department of Pediatrics, Division of Nephrology, Upstate Medical University, 750 E. Adams Street, Syracuse, NY 13210, USA. schurmas@upstate.edu
Pediatric Nephrology (Berlin, Germany)
|December 3, 2003
Summary
Neonatal Bartter syndrome (NBS) involves bone loss. Elevated Angiotensin II (AT II) in NBS stimulates basic-fibroblast growth factor (b-FGF), increasing bone resorption through prostaglandins.
Area of Science:
- Endocrinology and Metabolism
- Pediatric Nephrology
- Skeletal Biology
Background:
- Neonatal Bartter syndrome (NBS) is characterized by hypercalciuria, nephrocalcinosis, and osteopenia in children.
- A complex of basic-fibroblast growth factor (b-FGF) and glycosaminoglycan is found in NBS patients and increases bone resorption.
- Elevated Angiotensin II (AT II) levels are observed in Bartter syndrome and stimulate b-FGF synthesis in endothelial cells.
Purpose of the Study:
- To investigate the role of Angiotensin II (AT II) in bone resorption in neonatal Bartter syndrome (NBS).
- To determine the mechanism by which AT II affects calcium uptake in bone.
- To explore the potential involvement of basic-fibroblast growth factor (b-FGF) and prostaglandins in AT II-mediated bone changes.
Main Methods:
- Utilized a bone disc bioassay system to measure calcium uptake.
- Administered Angiotensin II (AT II) to cultured endothelial cells to assess b-FGF synthesis.
- Tested the effects of AT II, b-FGF monoclonal antibody, and indomethacin on calcium uptake in bone discs.
- In vivo experiments involved intraperitoneal injections of AT II in newborn rats, followed by bone disc bioassay.
Main Results:
- Addition of AT II (10(-8) M) significantly decreased calcium uptake into bone discs (E/C 0.60).
- The inhibitory effect of AT II on calcium uptake was neutralized by b-FGF monoclonal antibody and indomethacin.
- In vivo administration of AT II to rats markedly reduced calcium uptake in bone discs compared to controls.
- AT II demonstrated a dose-dependent decrease in calcium uptake in the bone disc bioassay.
Conclusions:
- Elevated Angiotensin II (AT II) directly decreases calcium uptake in bone.
- The effect of AT II on bone resorption is mediated by basic-fibroblast growth factor (b-FGF) and prostaglandins.
- These findings support a mechanism where AT II stimulates skeletal b-FGF synthesis, leading to increased bone resorption via a prostaglandin-dependent pathway in NBS.