title: Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice.
abstract: BACKGROUND
  Increased production of reactive oxygen species (ROSs) by angiotensin II (Ang II) is involved in the initiation and progression of cardiovascular diseases. NADPH oxidase is a major source of superoxide generated in vascular tissues. Although Nox1 has been identified in vascular smooth muscle cells as a new homolog of gp91phox (Nox2), a catalytic subunit of NADPH oxidase, the pathophysiological function of Nox1-derived ROSs has not been fully elucidated. To clarify the role of Nox1 in Ang II-mediated hypertension, we generated Nox1-deficient (-/Y) mice.
  
  
  RESULTS
  No difference in the baseline blood pressure was observed between Nox1(+/Y) and Nox1(-/Y). Infusion of Ang II induced a significant increase in mean blood pressure, accompanied by augmented expression of Nox1 mRNA and superoxide production in the aorta of Nox1(+/Y), whereas the elevation in blood pressure and production of superoxide were significantly blunted in Nox1(-/Y). Conversely, the infusion of pressor as well as subpressor doses of Ang II did elicit marked hypertrophy in the thoracic aorta of Nox1(-/Y) similar to Nox1(+/Y). Administration of a nitric oxide synthase inhibitor (L-NAME) to Nox1(+/Y) did not affect the Ang II-mediated increase in blood pressure, but it abolished the suppressed pressor response to Ang II in Nox1(-/Y). Finally, endothelium-dependent relaxation and the level of cGMP in the isolated aorta were preserved in Nox1(-/Y) infused with Ang II.
  
  
  CONCLUSIONS
  A pivotal role for ROSs derived from Nox1/NADPH oxidase was suggested in the pressor response to Ang II by reducing the bioavailability of nitric oxide.
authors.affiliation: Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Kuniharu
authors.initials: K
authors.lastname: Matsuno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Kazumi
authors.initials: K
authors.lastname: Iwata
authors.forename: Denan
authors.initials: D
authors.lastname: Jin
authors.forename: Masato
authors.initials: M
authors.lastname: Katsuyama
authors.forename: Masato
authors.initials: M
authors.lastname: Matsuki
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamanishi
authors.forename: Mizuo
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yabe-Nishimura
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency* / Q000235:genetics; D000074624:NADPH Oxidase 1; D009569:Nitric Oxide / Q000493:pharmacokinetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; D009569:Nitric Oxide; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614711:NOX1 protein, mouse