Role of Angiotensin II type 1 receptor on renal NAD(P)H oxidase, oxidative stress and inflammation in nitric oxide inhibition induced-hypertension.
Role of Angiotensin II type 1 receptor on renal NAD(P)H oxidase, oxidative stress and inflammation in nitric oxide inhibition induced-hypertension.
复制标题
DOI：
10.1016/j.lfs.2015.01.005
复制
发表时间：
2015-03-01
期刊：
影响因子：
6.1
通讯作者：
Romero F
中科院分区：
文献类型：
--
作者：
Rincón J;Correia D;Arcaya JL;Finol E;Fernández A;Pérez M;Yaguas K;Talavera E;Chávez M;Summer R;Romero F
肾素 - 血管紧张素系统（RAS）的激活、肾脏氧化应激和炎症在实验性高血压中持续存在。先前已有报道，用Nω - 硝基 - L - 精氨酸甲酯（L - NAME）抑制一氧化氮（NO）会导致高血压、血管紧张素II（Ang II）表达增加以及肾功能障碍。使用氯沙坦（一种血管紧张素II 1型受体（AT1R）拮抗剂）已被证明能有效降低高血压和减轻肾损伤；然而，在该实验模型中AT1R阻断降低肾损伤并使血压正常化的机制仍完全未知。本研究旨在验证以下假设：在L - NAME诱导的高血压过程中，AT1R激活促进肾脏NAD（P）H氧化酶上调、氧化应激和细胞因子产生。
将雄性Sprague - Dawley大鼠分为三组：L - NAME组，给予70mg/100ml的L - NAME；L - NAME + Los组，给予70mg/100ml的L - NAME和40mg/kg/天的氯沙坦；对照组，给予水而非L - NAME或L - NAME与氯沙坦。
两周后，L - NAME诱导高血压，肾脏AT1R、NAD（P）H氧化酶亚单位gp91、p22和p47过度表达，氧化应激水平、白细胞介素 - 6（IL - 6）和白细胞介素 - 17（IL - 17）升高。此外，我们还发现淋巴细胞和巨噬细胞在肾脏的积聚增加。氯沙坦治疗消除了gp91、p22、p47在肾脏的表达以及氧化应激，并降低了核因子 - κB的激活和IL - 6的表达。
这些研究结果表明，NO诱导的高血压与NADPH氧化酶上调、氧化应激产生以及关键炎症介质的过度表达有关。这些情况与AT1R的上调有关，这从使用AT1R阻断剂治疗后它们得到逆转可以证明。
Activation of the renin–angiotensin system (RAS), renal oxidative stress and inflammation are constantly present in experimental hypertension. Nitric oxide (NO) inhibition with Nw-nitro-L-arginine methyl ester (L-NAME) has previously been reported to produce hypertension, increased expression of Angiotensin II (Ang II) and renal dysfunction. The use of Losartan, an Ang II type 1 receptor (AT1R) antagonist has proven to be effective reducing hypertension and renal damage; however, the mechanism by which AT1R blockade reduced kidney injury and normalizes blood pressure in this experimental model is still complete unknown. The current study was designed to test the hypothesis that AT1R activation promotes renal NAD(P)H oxidase up-regulation, oxidative stress and cytokine production during L-NAME induced-hypertension. Male Sprague–Dawley rats were distributed in three groups: L-NAME, receiving 70 mg/100 ml of L-NAME, L-NAME + Los, receiving 70 mg/100 ml of L-NAME and 40 mg/kg/day of Losartan; and Controls, receiving water instead of L-NAME or L-NAME and Losartan. After two weeks, L-NAME induced high blood pressure, renal overexpression of AT1R, NAD(P)H oxidase sub-units gp91, p22 and p47, increased levels of oxidative stress, interleukin-6 (IL-6) and interleukin-17 (IL-17). Also, we found increased renal accumulation of lymphocytes and macrophages. Losartan treatment abolished the renal expression of gp91, p22, p47, oxidative stress and reduced NF-κB activation and IL-6 expression. These findings indicate that NO induced-hypertension is associated with up-regulation of NADPH oxidase, oxidative stress production and overexpression of key inflammatory mediators. These events are associated with up-regulation of AT1R, as evidenced by their reversal with AT1R blocker treatment.
登录
查看更多内容
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
8.3
作者：
Barhoumi, Tlili;Kasal, Daniel A.;Schiffrin, Ernesto L.
通讯作者：
Schiffrin, Ernesto L.
影响因子：
13.6
作者：
Herrera, Jose;Ferrebuz, Atiho;Rodriguez-Iturbe, Bernardo
通讯作者：
Rodriguez-Iturbe, Bernardo
DOI：
10.1152/ajprenal.00218.2001
发表时间：
2002-06-01
影响因子：
4.2
作者：
Li, N;Yi, FX;Zou, AP
通讯作者：
Zou, AP
转化生长因子β对于 Th17 细胞分化的分子协调是不可或缺的。
影响因子：
15.3
作者：
Das, Jyoti;Ren, Guangwen;Zhang, Liying;Roberts, Arthur I.;Zhao, Xin;Bothwell, Alfred L. M.;Van Kaer, Luc;Shi, Yufang;Das, Gobardhan
通讯作者：
Das, Gobardhan