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Adaptation to reduction in renal mass in mice: effects of tempol on renal growth, hemodynamics and oxygenation
Author(s) -
Lai Enyin,
Onozato Maristela L,
Rudolph Earl H,
Solis Glenn,
Aslam Shakil,
Luo Zaiming,
Welch William J,
Wilcox Christopher S.
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.667.1
Compensatory growth, hyperfiltration and impaired oxygen utilization are responses to chronic kidney disease. We tested the hypothesis that these depend on oxidative stress. C57Bl6 mice were subjected to surgical reduction in renal mass or sham operation and fed a high salt diet with or without tempol for 3 months. Tempol corrected the increased excretion of 8‐isoprostane and plasma creatinine, and reduced the blood pressure and renal vascular resistance. Tempol increased the tubular sodium transport but reduced the renal oxygen extraction and oxygen usage, thereby correcting the impaired oxygen usage for tubular sodium transport. Tempol corrected the hypoxia in the renal cortex (Sham 42±3, tempol 62±5, reduced renal mass 29±4, reduced renal mass plus tempol 51±4 mmHg). Tempol enhanced the glomerular volume and the glomerular filtration rate per residual nephron. These mice did not exhibit glomerulosclerosis but tempol prevented the increased tubulointerstitial fibrosis and expression of transforming growth factor beta. We concluded that this mouse model of reduced renal mass developed oxidative stress that contributed to the inefficient use of oxygen for tubular sodium transport, the renal cortical hypoxia, interstitial fibrosis and transforming growth factor beta expression and limited the full compensatory renal vasodilation and glomerular growth that contributed to nephron hyperfiltration.