p47phox Is Required for Afferent Arteriolar Contractile Responses to Angiotensin II and Perfusion Pressure in Mice
Myogenic and angiotensin contractions of afferent arterioles generate reactive oxygen species. Resistance vessels express neutrophil oxidase-2 and -4. Angiotensin II activates p47phox/neutrophil oxidase-2, whereas it downregulates NOX-4. Therefore, we tested the hypothesis that p47phox enhances afferent arteriolar angiotensin contractions. Angiotensin II infusion in p47phox +/+ but not −/− mice increased renal cortical NADPH oxidase activity (7±1–12±1 [P<0.01] versus 5±1–7±1 103·RLU·min−1·μg protein−1 [P value not significant]), mean arterial pressure (77±2–91±2 [P<0.005] versus 74±2–77±1 mm Hg [P value not significant]), and renal vascular resistance (7.5±0.4–10.1±0.7 [P<0.01] versus 7.9±0.4–8.3±0.4 mm Hg/mL · min−1 · gram kidney weight−1 [P value not significant]). Afferent arterioles from p47phox −/− mice had a lesser myogenic response (3.1±0.4 versus 1.4±0.2 dynes · cm−1 · mm Hg−1; P<0.02) and a lesser (P<0.05) contraction to 10−6 M angiotensin II (diameter change +/+: 9.3±0.2–3.4±0.6 μm versus −/−: 9.9±0.6–7.5±0.4 μm). Angiotensin and increased perfusion pressure generated significantly (P<0.05) more reactive oxygen species in p47phox +/+ than −/− arterioles. Angiotensin II infusion increased the maximum responsiveness of afferent arterioles from p47phox +/+ mice to 10−6 M angiotensin II yet decreased the response in p47phox −/− mice. The angiotensin infusion increased the sensitivity to angiotensin II only in p47phox +/+ mice. We conclude that p47phox is required to enhance renal NADPH oxidase activity and basal afferent arteriolar myogenic and angiotensin II contractions and to switch afferent arteriolar tachyphylaxis to sensitization to angiotensin during a prolonged angiotensin infusion. These effects likely contribute to hypertension and renal vasoconstriction during infusion of angiotensin II.
- Received October 3, 2011.
- Revision received October 28, 2011.
- Accepted November 22, 2011.
- © 2011 American Heart Association, Inc.