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(Hypertension. 2004;43:335.)
© 2004 American Heart Association, Inc.

Scientific Contribution

Assessment of Renal Functional Phenotype in Mice Lacking gp91^PHOX Subunit of NAD(P)H Oxidase

From the Department of Physiology, Tulane University Health Sciences Center, New Orleans, La.

Correspondence to Dr Dewan S.A. Majid, Associate Professor, Department of Physiology (SL 39), Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112. E-mail majid{at}tulane.edu

To determine the role of endogenous superoxide (O₂^-) in the kidney, we assessed renal hemodynamics and excretory function in gp91^PHOX (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 gp91^PHOX, 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^-.

Key Words: angiotensin II • superoxide • renal circulation

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