Nox1 is involved in angiotensin II-mediated hypertension - A study in Nox1-deficient mice
Nox1 is involved in angiotensin II-mediated hypertension - A study in Nox1-deficient mice
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DOI：
10.1161/circulationaha.105.573709
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发表时间：
2005-10-25
期刊：
影响因子：
37.8
通讯作者：
Yabe-Nishimura, C
中科院分区：
文献类型：
--
作者：
Matsuno, K;Yamada, H;Yabe-Nishimura, C
背景-血管紧张素II(Ang II)增加活性氧物种(ROS)的产生与心血管疾病的发生和发展有关。NADPH氧化酶是血管组织中产生的超氧化物的主要来源。尽管Nox1在血管平滑肌细胞中已被鉴定为NADPH氧化酶催化亚基gp91Phox(NOX2)的新同系物，但其病理生理功能尚未完全阐明。为了阐明Nox1在Ang II介导的高血压中的作用，我们制备了Nox1缺陷型((-/Y))小鼠。方法和结果：NOx1(+/Y)和Nox1(+/Y)的基础血压没有差异。输注Ang II可引起平均血压显著升高，同时伴随着Nox1(+/Y)的表达增加和主动脉中超氧化物的产生，而Nox1(-/Y)的血压升高和超氧化物的产生明显减弱。相反，升压和降压剂量的血管紧张素转换酶II确实引起NOX1(-/Y)胸主动脉明显肥厚，与NOX1(+/Y)相似。向NOX1(+/Y)注入一氧化氮合酶抑制剂(L-NAME)不影响血管紧张素转换酶II介导的血压升高，但可阻断NOX1(-/Y)对血管紧张素转换酶II的抑制反应。结论NOX1/NADPH氧化酶可能通过降低NO的生物利用度，在Ang II的升压反应中发挥重要作用。
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.