Cited by 470Nitric Oxide and Endothelin EffectsRenin-Angiotensin System StudiesEicosanoids and Hypertension Pharmacology

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Nox1 Is Involved in Angiotensin II–Mediated Hypertension: A Study in Nox1-Deficient Mice

Matsuno, Kuniharu, Yamada, Hiroyuki, Iwata, Kazumi, Jin, Denan, Katsuyama, Masato, Matsuki, Masato, Takai, Shinji, Yamanishi, Kiyofumi, Miyazaki, Mizuo, Matsubara, Hiroaki, Yabe-Nishimura, Chihiro·2005·Circulation

DOI 10.1161/circulationaha.105.573709

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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. Methods and 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.

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Authors: Matsuno, K., Yamada, H., Iwata, K., Jin, D., Katsuyama, M., Matsuki, M., Takai, S., Yamanishi, K., Miyazaki, M., Matsubara, H., & Yabe-Nishimura, C.
Affiliations: Kyoto Prefectural University of Medicine (JP)
From the Department of Pharmacology (K.M., K.I., M.K., C.Y.-N.), Department of Cardiovascular Medicine (H.Y., H.M.), and Department of Dermatology (M. Matsuki, K.Y.), Kyoto Prefectural University of Medicine, Kyoto; and the Department of Pharmacology, Osaka Medical College (D.J., S.T., M. Miyazaki), Osaka, Japan. Drs Matsuki and Yamanishi are now at the Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan.
ORCID: Yamada, Hiroyuki
Iwata, Kazumi
Jin, Denan
Katsuyama, Masato
Takai, Shinji
Yamanishi, Kiyofumi
Matsubara, Hiroaki
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2005-10-25
Volume: 112
Issue: 17
Pages: 2677-2685
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.105.573709
OpenAlex: W2160571418
Cited by: 470
References: 30
Citations by year: 2026: 7 · 2025: 12 · 2024: 16 · 2023: 18 · 2022: 12 · 2021: 13 · 2020: 11 · 2019: 15 · 2018: 16 · 2017: 25 · 2016: 29 · 2015: 30 · 2014: 32 · 2013: 27 · 2012: 39
FWCI: 16.18
Type: journal article
Language: en
Open access: closed
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords: NOX1, angiotensin II, hypertension, reactive oxygen species, NADPH oxidase, superoxide, nitric oxide bioavailability, pressor response, nitric oxide synthase, cyclic GMP, endothelium-dependent relaxation
MeSH terms: NADPH Oxidase 1, Angiotensin II, Animals, Biological Availability, Blood Pressure, Disease Models, Animal, Heart Rate, Hypertension, Mice, Inbred Strains, Muscle, Smooth, Vascular, NADH, NADPH Oxidoreductases, Nitric Oxide, Reactive Oxygen Species, Mice, Knockout, Mice

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Nox1 Is Involved in Angiotensin II–Mediated Hypertension: A Study in Nox1-Deficient Mice

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