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.