p47 phox 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 p47 phox /neutrophil oxidase-2, whereas it downregulates NOX-4. Therefore, we tested the hypothesis that p47 phox enhances a...

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Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2012-02, Vol.59 (2), p.415-420
Main Authors: Lai, En Yin, Solis, Glenn, Luo, Zaiming, Carlstrom, Mattias, Sandberg, Kathryn, Holland, Steven, Wellstein, Anton, Welch, William J., Wilcox, Christopher S.
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cited_by cdi_FETCH-LOGICAL-c1981-ee9210d67eaf30e1549502112141634add4863a00260c607f54971099ec37ea33
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container_end_page 420
container_issue 2
container_start_page 415
container_title Hypertension (Dallas, Tex. 1979)
container_volume 59
creator Lai, En Yin
Solis, Glenn
Luo, Zaiming
Carlstrom, Mattias
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Wellstein, Anton
Welch, William J.
Wilcox, Christopher S.
description Myogenic and angiotensin contractions of afferent arterioles generate reactive oxygen species. Resistance vessels express neutrophil oxidase-2 and -4. Angiotensin II activates p47 phox /neutrophil oxidase-2, whereas it downregulates NOX-4. Therefore, we tested the hypothesis that p47 phox enhances afferent arteriolar angiotensin contractions. Angiotensin II infusion in p47 phox +/+ but not −/− mice increased renal cortical NADPH oxidase activity (7±1–12±1 [ P
doi_str_mv 10.1161/HYPERTENSIONAHA.111.184291
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Resistance vessels express neutrophil oxidase-2 and -4. Angiotensin II activates p47 phox /neutrophil oxidase-2, whereas it downregulates NOX-4. Therefore, we tested the hypothesis that p47 phox enhances afferent arteriolar angiotensin contractions. Angiotensin II infusion in p47 phox +/+ but not −/− mice increased renal cortical NADPH oxidase activity (7±1–12±1 [ P <0.01] versus 5±1–7±1 10 3 · 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 p47 phox −/− 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 p47 phox +/+ than −/− arterioles. Angiotensin II infusion increased the maximum responsiveness of afferent arterioles from p47 phox +/+ mice to 10 −6 M angiotensin II yet decreased the response in p47 phox −/− mice. The angiotensin infusion increased the sensitivity to angiotensin II only in p47 phox +/+ mice. We conclude that p47 phox 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. 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Resistance vessels express neutrophil oxidase-2 and -4. Angiotensin II activates p47 phox /neutrophil oxidase-2, whereas it downregulates NOX-4. Therefore, we tested the hypothesis that p47 phox enhances afferent arteriolar angiotensin contractions. Angiotensin II infusion in p47 phox +/+ but not −/− mice increased renal cortical NADPH oxidase activity (7±1–12±1 [ P <0.01] versus 5±1–7±1 10 3 · 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 p47 phox −/− 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 p47 phox +/+ than −/− arterioles. Angiotensin II infusion increased the maximum responsiveness of afferent arterioles from p47 phox +/+ mice to 10 −6 M angiotensin II yet decreased the response in p47 phox −/− mice. The angiotensin infusion increased the sensitivity to angiotensin II only in p47 phox +/+ mice. We conclude that p47 phox 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. 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Resistance vessels express neutrophil oxidase-2 and -4. Angiotensin II activates p47 phox /neutrophil oxidase-2, whereas it downregulates NOX-4. Therefore, we tested the hypothesis that p47 phox enhances afferent arteriolar angiotensin contractions. Angiotensin II infusion in p47 phox +/+ but not −/− mice increased renal cortical NADPH oxidase activity (7±1–12±1 [ P <0.01] versus 5±1–7±1 10 3 · 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 p47 phox −/− 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 p47 phox +/+ than −/− arterioles. Angiotensin II infusion increased the maximum responsiveness of afferent arterioles from p47 phox +/+ mice to 10 −6 M angiotensin II yet decreased the response in p47 phox −/− mice. The angiotensin infusion increased the sensitivity to angiotensin II only in p47 phox +/+ mice. We conclude that p47 phox 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.]]></abstract><doi>10.1161/HYPERTENSIONAHA.111.184291</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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