Premium
Increased mitochondrial uncoupling results in renal tissue hypoxia and proteinuria
Author(s) -
Friederich Malou,
Nangaku Masaomi,
Fasching Angelica,
Hansell Peter,
Palm Fredrik
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.664.4
Subject(s) - endocrinology , kidney , renal function , medicine , renal blood flow , chemistry , proteinuria , hypoxia (environmental) , urinary system , oxygen , organic chemistry
Diabetes results in renal tissue hypoxia primarily due to increased mitochondrial oxygen utilization induced by excessive oxidative stress. However, it is unclear if the tissue hypoxia per se results in proteinuria. We therefore induced increased mitochondrial oxygen usage by administrating the chemical mitochondrial uncoupler dinitrophenol (DNP; 30 mg/24h/kg dissolved in 0.2 ml methyl cellulose by oral gavage), or vehicle, to healthy rats for 4 weeks. We thereafter measured glomerular filtration rate (GFR; inulin clearance), renal blood flow (RBF; transonic flow probe), tissue PO2 (microelectrodes) and urinary protein excretion. Administration of DNP did not alter blood pressure (94±9 vs. 99±3 mmHg), RBF (9±1 vs. 10±1 ml/min/kidney), kidney weight (1.3±0.1 vs. 1.4±0.1 g), urinary flow (1.9±0.0.3 vs. 2.6±0.7 μl/min/kidney), or GFR (1.3±0.2 vs. 1.5±0.1 ml/min/kidney), but reduced cortical oxygenation (29± 1 vs. 44±1 mmHg, p<0.05), and increased proteinuria (77±8 vs. 47±8 μg/min/kidney, p<0.05) during Inactin anesthesia. In conclusion, increased mitochondrial oxygen usage results in renal hypoxia and proteinuria. Similar mitochondrial alterations, including increased oxygen usage, occur in the diabetic kidney. The resulting tissue hypoxia may be a mechanism for the increased proteinuria commonly associated with diabetes.