Document Detail

p47(phox) is required for afferent arteriolar contractile responses to angiotensin II and perfusion pressure in mice.
MedLine Citation:
PMID:  22184329     Owner:  NLM     Status:  MEDLINE    
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<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.
En Yin Lai; Glenn Solis; Zaiming Luo; Mattias Carlstrom; Kathryn Sandberg; Steven Holland; Anton Wellstein; William J Welch; Christopher S Wilcox
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-19
Journal Detail:
Title:  Hypertension     Volume:  59     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-25     Completed Date:  2012-04-20     Revised Date:  2013-12-09    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  415-20     Citation Subset:  IM    
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MeSH Terms
Angiotensin II / pharmacology*
Arterioles / drug effects*,  physiology*
Blood Pressure / drug effects,  physiology
Disease Models, Animal
Dose-Response Relationship, Drug
Hypertension / metabolism,  physiopathology
Mice, Inbred C57BL
Mice, Knockout
NADPH Oxidase / deficiency,  genetics,  metabolism,  physiology*
Reactive Oxygen Species / metabolism
Vascular Resistance / drug effects,  physiology*
Vasoconstriction / drug effects,  physiology*
Vasoconstrictor Agents / pharmacology
Grant Support
DK-036079/DK/NIDDK NIH HHS; DK-049870/DK/NIDDK NIH HHS; HL-68686/HL/NHLBI NIH HHS; P01 HL068686/HL/NHLBI NIH HHS; P01 HL068686-10/HL/NHLBI NIH HHS; R01 DK049870/DK/NIDDK NIH HHS; R01 DK049870-17/DK/NIDDK NIH HHS; R01 DK049870-18/DK/NIDDK NIH HHS; R01 HL089583-05/HL/NHLBI NIH HHS; R37 DK036079-25/DK/NIDDK NIH HHS; R37 DK036079-26/DK/NIDDK NIH HHS
Reg. No./Substance:
0/Reactive Oxygen Species; 0/Vasoconstrictor Agents; 11128-99-7/Angiotensin II; EC Oxidase; EC cytosolic factor 1

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