| First Author | Matsuno K | Year | 2005 |
| Journal | Circulation | Volume | 112 |
| Issue | 17 | Pages | 2677-85 |
| PubMed ID | 16246966 | Mgi Jnum | J:116837 |
| Mgi Id | MGI:3695092 | Doi | 10.1161/CIRCULATIONAHA.105.573709 |
| Citation | Matsuno K, et al. (2005) Nox1 is involved in angiotensin II-mediated hypertension: a study in Nox1-deficient mice. Circulation 112(17):2677-85 |
| abstractText | 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. |
