The α(II)̄(S)[̄(MDD)] mouse is a useful model for studying renal functional abnormalities in sickle cell disease. We previously reported that these mice develop a urine concentrating defect when chronically exposed to a low oxygen environment. In the present study, we measured glomerular filtration rate (GFR), urinary excretion of NO2 + NO3, the stable products of nitric oxide (NO), and the abundance of endothelial constitutive nitric and synthase (NOS III) and inducible nitric oxide synthase (NOS II) in the kidneys by Western blot. Immunohistochemistry was also carried out. We found that GFR is significantly higher in the transgenic mice in than in controls. The Urinary NO2 + NO3/creatinine ratio was also higher. The Western blots revealed that both NOS III and NOS II are markedly increased in the kidneys of transgenic mice as compared to normal control mice. Immunohistochemistry localized NOS III reactivity in proximal convoluted cells in cortex of control and α(II)β(S)[β(MDD)] mice NOS II immunostaining was not seen in control mice but was clearly evident in glomeruli and distal nephron segments of the α(II)β(S)(MDD)[β(MDD)] mice. These observations suggest that NOS II is induced in glomeruli and distal nephron of the α(II)β(S)[b(MDD)] mice. An increase in synthesis of NO may occur in the glomeruli as a result of NOS II induction, and this may contribute to the hyperfiltration in these mice.
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