Assessment of Renal Functional Phenotype in Mice Lacking gp91PHOX Subunit of NAD(P)H Oxidase

Abstract

To determine the role of endogenous superoxide (O2−) in the kidney, we assessed renal hemodynamics and excretory function in gp91PHOX (a NAD(P)H oxidase subunit) gene knockout (KO) mice and compared these findings with those of wild-type (WT) strain C57BL/6 mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearances respectively in anesthetized mice (n=8 in each group). There were higher baseline RBF (4.3±0.4 versus 2.5±0.2 mL/min per gram; P <0.002) and lower renal vascular resistance (RVR) (16±1.4 versus 29±2.3 mm Hg/mL/min per gram; P <0.0001) in KO compared with WT without a significant difference in mean arterial pressure (MAP) (67±2 versus 71±2 mm Hg) and GFR (0.66±0.09 versus 0.73±0.05 mL/min per gram) between the strains. Intravenous infusion of angiotensin II (Ang II) (2 ng/min per gram of body weight) for 30 minutes caused a lesser degree of decreases in RBF (−8% versus −33%) and of increases in RVR (+73% versus +173%) in KO compared with WT. GFR was increased (43%) in KO but not in WT during Ang II infusion. Urinary excretion of nitrate/nitrite was higher in conscious KO (n=5) than in WT (n=5), indicating an increase in nitric oxide bioavailability that could be the cause of high RBF and low RVR in KO. These data indicate that gp91PHOX, a subunit of NAD(P)H oxidase, plays a regulatory role in the maintenance of renal vascular tone. These results also suggest that the mechanism of Ang II-mediated renal vascular action involves concomitant generation of O2−. © 2004 Lippincott Williams & Wilkins, Inc.