Renal nitric oxide synthases in transgenic sickle cell mice.
The alpha H beta S [beta 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 s+ NO3, the stable products of nitric oxide (NO), and the abundance of endothelial constitutive nitric oxide 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 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 the cortex of control and alpha H beta S [beta MDD] mice. NOS II immunostaining was not seen in control mice but was clearly evident in glomeruli and distal nephron segments of the alpha H beta S [beta MDD] mice. These observations suggest that NOS II is induced in glomeruli and distal nephrons 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.
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Department of Medicine, Montefiore Medical Center, Bronx, New York, USA.
Aynedjian
H S
HS
Qiu
J H
JH
Osei
S Y
SY
Ahima
R S
RS
Fabry
M E
ME
Nagel
R L
RL
D000755:Anemia, Sickle Cell / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D015153:Blotting, Western; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009929:Organ Size
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase