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HIF activation fails to restore renal oxygenation in already established diabetic nephropathy
Author(s) -
Palm Fredrik,
Nangaku Masaomi,
Fasching Angelica,
Nordquist Lina,
Hansell Peter
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.664.8
Subject(s) - diabetic nephropathy , diabetes mellitus , hypoxia (environmental) , renal cortex , endocrinology , kidney , medicine , nephropathy , medulla , renal medulla , renal function , oxygenation , chemistry , oxygen , organic chemistry
Diabetic kidneys have reduced oxygenation (pO 2 ), which is a proposed mechanism for development of diabetic nephropathy. Renal hypoxia in diabetes does not result in a counteracting hypoxic gene response, but we have reported that activation of hypoxia‐inducible factors (HIF), using the chemical hypoxiamimetic CoCl 2 , prevents hypoxia, fibrosis and proteinuria in diabetic kidneys. However, it is unknown if HIF activation reverse renal hypoxia in established nephropathy. Therefore, 5‐week diabetic rats were treated with CoCl 2 for 4 additional weeks and compared to corresponding untreated diabetic rats. Kidney function, pO 2 and oxygen consumption (QO 2 ) were measured under Inactin‐anesthesia. Different diabetes duration resulted in similar renal hypoxia (cortex 31–34, medulla 18–19 mmHg) compared to controls (cortex 45±2, medulla 30±1 mmHg). Chronic CoCl 2 treatment to diabetics prevented renal hypoxia (cortex 42±1 and medulla 39±1 mmHg), whereas CoCl 2 treatment started 5 weeks after diabetes induction had no effect (cortex 35±1, medulla 22±1 mmHg). Renal hypoxia in diabetes is due to increased QO 2 (11.4±2.8 vs. 22.5±3.5 μmol/min). CoCl 2 administration from onset of diabetes was preventive (16.8±3.5 μmol/min), but had no effect in established nephropathy (25.6±2.9 μmol/min). In conclusion, HIF activation fails to reverse hypoxia in established diabetic nephropathy.