Submitted on July 31, 2008
Revised on September 30, 2008
Accepted on October 13, 2008
NADPH OXIDASE CONTRIBUTES TO RENAL DAMAGE AND DYSFUNCTION IN DAHL SALT-SENSITIVE HYPERTENSION
Niu Tian1, Rebecca S. Moore1, William E. Phillips1, Lin Lin1, Sharkeshia Jordan Braddy1, Janelle S. Pryor1, Rachel L. Stockstill1, Michael D Hughson1, and R. Davis Manning, Jr.1*
1 University of Mississippi Medical Center
* To whom correspondence should be addressed. E-mail: dmanning{at}physiology.umsmed.edu.
The goal of this study was to test the hypothesis that NADPH oxidase contributes importantly to renal cortical oxidative stress and inflammation, as well as renal damage and dysfunction, and increases in arterial pressure. Fifty-four 7-to 8-week old Dahl S or R/Rapp strain rats were maintained for 5 weeks on a high sodium (8%) or high sodium + apocynin (1.5 mmol/L in drinking H2O). Arterial and venous catheters were implanted at day 21. By day 35 in the high Na S rats, mRNA expression of renal cortical gp91 phox, p22 phox, p47 phox and p67 phox NADPH subunits in Dahl S rats increased markedly, and treatment of high Na S rats with, the NADPH oxidase inhibitor, apocynin resulted in significant decreases in mRNA expression of these NADPH oxidase subunits. At the same time in apocynin-treated S rats, the renal cortical GSH/GSSG ratio increased, renal cortical O2•-release and NADPH oxidase activity decreased, and renal glomerular and interstitial damage markedly fell. Apocynin also decreased renal cortical monocyte/macrophage infiltration, and apocynin but not the XO inhibitor, allopurinol, attenuated decreases in renal hemodynamics and lowered arterial pressure. These data suggest that NADPH oxidase plays an important role in causing renal cortical oxidative stress and inflammation which lead to decreases in renal hemodynamics, renal cortical damage and increases in arterial pressure.
