Assessment of renal functional phenotype in mice lacking gp91PHOX subunit of NAD(P)H oxidase.
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-.
Haque
Mohammed Z
MZ
Department of Physiology, Tulane University Health Sciences Center, New Orleans, La 70112, USA.
Majid
Dewan S A
DS
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013481:Superoxides / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
D008562:Membrane Glycoproteins; D021122:Protein Subunits; D013481:Superoxides; D000804:Angiotensin II; D012964:Sodium; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases