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Cardiovascular-Renal Mechanisms in Health and Disease

p22^phox in the macula densa regulates single nephron GFR during angiotensin II infusion in rats

Department of Medicine, Georgetown University, Washington, District of Columbia

Submitted 7 September 2006 ; accepted in final form 21 December 2006

Angiotensin II (ANG II) infusion increases renal superoxide (O₂^–) and enhances renal vasoconstriction via macula densa (MD) regulation of tubuloglomerular feedback, but the mechanism is unclear. We targeted the p22^phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) with small-interfering RNA (siRNA) to reduce NADPH oxidase activity and blood pressure response to ANG II in rats. We compared single nephron glomerular filtration rate (SNGFR) in samples collected from the proximal tubule (PT), which interrupts delivery to the 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^–1·min^–1 for 7 days) 2 days after intravenous injection of vehicle or siRNA directed to p22^phox to test the hypothesis that p22^phox mediates MD regulation of SNGFR during ANG II. The regulation of SNGFR by MD, 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; not significant) 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 p22^phox and NADPH oxidase regulate the SNGFR during ANG II infusion via MD-dependent mechanisms.

renal function; oxidative stress; hypertension; tubuloglomerular feedback; glomerular filtration rate