Submitted on September 7, 2006
Accepted on December 21, 2006
p22phox in the macula densa regulates single nephron GFR during angiotensin II infusion in rats
Pouneh Nouri1, Pritmohinder S. Gill1, Min Li1, Christopher S. Wilcox1, and William J. Welch1*
1 Cardiovascular-Kidney Institute and Division of Nephrology and Hypertension, Georgetown University, Washington, District of Columbia, United States
* To whom correspondence should be addressed. E-mail: welchw{at}georgetown.edu.
Angiotensin II (Ang II) infusion increases renal superoxide (O2-.), and enhances renal vasoconstriction via macula densa regulation of tubuloglomerular feedback (TGF), but the mechanism is unclear. We targeted the p22phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) with small interfering RNA (siRNA) to reduce NADPH oxidase activity and BP response to Ang II in rats. We compared single nephron GFR (SNGFR) in samples collected from the proximal tubule (PT), which interrupts delivery to the macula densa (MD) and from the distal tubule (DT), which maintains delivery to the MD, to assess MD regulation of GFR. SNGFR was measured in control and Ang II infused rats (200 ng/kg/min X 7 days), 2 days after IV injection of vehicle or siRNA directed to p22phox to test the hypothesis that p22phox mediates MD regulation of SNGFR during Ang II. The regulation of SNGFR by macula densa, determined by PT SNGFR-DT SNGFR was not altered by siRNA in control rats (Control + Vehicle: 13±1, n=8; Control siRNA: 12±2 nl/min, n=8, NS), but was reduced by siRNA in Ang II treated rats (Ang II + Vehicle: 13±2, n=7; Ang II + siRNA: 7±1 nl/min, n=8, p<0.05). We conclude that p22phox and NADPH oxidase regulate the SNGFR during Ang II infusion via macula densa-dependent mechanisms.
