Key result
Nox1 deficiency blunts Angiotensin II-induced blood pressure elevation and superoxide production in mice.
Why the study?
The pathophysiological function of Nox1-derived reactive oxygen species in angiotensin II-mediated hypertension has not been fully elucidated.
Does Nox1 deficiency reduce Angiotensin II-mediated hypertension in mice?
Does Nox1 deficiency reduce Angiotensin II-mediated hypertension in mice?
Nox1-derived reactive oxygen species are pivotal in the pressor response to Angiotensin II by reducing nitric oxide bioavailability.
Nox1 inhibition merits further preclinical testing; leaves open translation to human hypertension therapy.
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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Matsuno et al. (2005) studied Angiotensin II-mediated hypertension. Nox1 deficiency vs. Wild-type Nox1(+/Y) was evaluated on Blood pressure elevation and superoxide production. Nox1 deficiency significantly blunted the elevation in blood pressure and superoxide production induced by Angiotensin II infusion compared to wild-type mice.
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