Young patients with sickle cell disease often manifest glomerular hyperfiltration. The transgenic mouse model of sickle cell disease, ags|B!j h a similar functional abnormality. In order to study the role of nitric oxide (NO) in the hyperfiltration, we measured the abundance and localization of endothelial constitutive (NOS III) and inducihle (NOS II) isoforms in the kidneys of these mice. Methods used were Western blot and immunohistochemistry. NOS III stained extensively in cortical convoluted tubule epithelial cells of normal mice, and was more widespread and intense in the cortex and medulla of aHgi[MDc,| nce inducjbie NOS (NOS II) was not seen in the kidney of control mice, but was found in cortical distal tubules and medullary tubules of ar"[IDI>J mice. Chronic exposure to 10% O2 resulted in d£ 00X0. NOS II staining in control mice but no change in NOS III. Western blots showed significantly increased abundance of both NOS III and NOS II in the o"s[MDD] mice and further increases in response to hypoxia. We postulate that tissue hypoxia due to vasoocclusion and shear stress induce NOS II and NOS in respectively in a"8I[8>'°°l mice. Increased renal NO synthesis may contribute to hyperfiltration in sickle cell disease.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology