p22phox in the macula densa regulates single nephron GFR during angiotensin II infusion in rats.
Angiotensin II (ANG II) infusion increases renal superoxide (O(2)(-)) 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.
Nouri
Pouneh
P
Department of Medicine, Georgetown University, Washington, District of Columbia 20057, USA.
Gill
Pritmohinder
P
Li
Min
M
Wilcox
Christopher S
CS
Welch
William J
WJ
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006977:Hypertension, Renal / Q000378:metabolism / Q000503:physiopathology; D007606:Juxtaglomerular Apparatus / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009399:Nephrons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019255:NADPH Oxidases; C515768:Cyba protein, rat