Clinical and experimental studies show that angiotensin II (AngII) promotes vascular pathology via activation of AngII type 1 receptors (AT1Rs). We recently reported that NP‐6A4, a selective peptide agonist for AngII type 2 receptor (AT2R), exerts protective effects on human vascular cells subjected to serum starvation or doxorubicin exposure. In this study, we investigated whether NP‐6A4–induced AT2R activation could mitigate AngII‐induced abdominal aortic aneurism (AAA) using AngII‐treated Apoe^−/− mice. Male Apoe^−/− mice were infused with AngII (1 µg/kg/min) by implanting osmotic pumps subcutaneously for 28 days. A subset of mice was pre‐treated subcutaneously with NP‐6A4 (2.5 mg/kg/day) or vehicle for 14 days prior to AngII, and treatments were continued for 28 days. NP‐6A4 significantly reduced aortic stiffness of the abdominal aorta induced by AngII as determined by ultrasound functional analyses and histochemical analyses. NP‐6A4 also increased nitric oxide bioavailability in aortic tissues and suppressed AngII‐induced increases in monocyte chemotactic protein‐1, osteopontin and proteolytic activity of the aorta. However, NP‐6A4 did not affect maximal intraluminal aortic diameter or AAA incidences significantly. These data suggest that the effects of AT2R agonist on vascular pathologies are selective, affecting the aortic stiffness and proteolytic activity without affecting the size of AAA.

中文翻译：

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AT2R激动剂NP-6A4可减轻动脉瘤小鼠模型的主动脉僵硬和蛋白水解活性。

临床和实验研究表明，血管紧张素II（AngII）通过激活AngII 1型受体（AT1Rs）促进血管病变。我们最近报道说，NP-6A4是AngII 2型受体（AT2R）的选择性肽激动剂，对遭受血清饥饿或阿霉素暴露的人血管细胞具有保护作用。在这项研究中，我们研究了使用AngII治疗的Apoe ^-/- 小鼠，NP-6A4诱导的AT2R活化是否可以缓解AngII诱导的腹主动脉瘤（AAA）。男APOE ^{- / -} 通过皮下植入渗透泵28天，向小鼠注入AngII（1 µg / kg / min）。在AngII之前，对一部分小鼠进行NP-6A4（2.5 mg / kg /天）或载体的皮下预处理14天，并继续治疗28天。超声功能分析和组织化学分析表明，NP-6A4显着降低了由AngII引起的腹主动脉的主动脉僵硬度。NP-6A4还增加了主动脉组织中一氧化氮的生物利用度，并抑制了AngII诱导的单核细胞趋化蛋白-1，骨桥蛋白和主动脉蛋白水解活性的增加。但是，NP-6A4不会显着影响最大腔内主动脉直径或AAA发生率。这些数据表明，AT2R激动剂对血管病理的影响是选择性的，