RENAL NITRIC-OXIDE SYNTHASES IN TRANSGENIC SICKLE-CELL MICE

The alpha(H) beta(S)[beta(MDD)] mouse is a useful model for studying r enal functional abnormalities in sickle cell disease. We previously re ported that these mice develop a urine concentrating defect when chron ically exposed to a low oxygen environment. In the present study, we m easured glomerular filtration rate (GFR), urinary excretion of NO2 + N O3, the stable products of nitric oxide (NO), and the abundance of end othelial constitutive nitric oxide synthase (NOS III) and inducible ni tric oxide synthase (NOS II) in the kidneys by Western blot. Immunohis tochemistry was also carried out. We found that GFR is significantly h igher in the transgenic mice than in controls. The urinary NO2 + NO3/c reatinine 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 localiz ed NOS III reactivity in proximal convoluted cells in the cortex of co ntrol and alpha(H) beta(S)[beta(MDD)] mice. NOS II immunostaining was not seen in control mite but was clearly evident in glomeruli and dist al nephron segments of the alpha(H) beta(S)[beta(MDD)] mice. These obs ervations suggest that NOS II is induced in glomeruli and distal nephr ons of the alpha(H) beta(S)[beta(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.