Oxidative stress, inflammation, and hypertension constitute a self-perpetuating vicious circle to exacerbate hypertension and subsequent hypertensive cardiac hypertrophy. NADPH oxidase (Nox) 1/4 inhibitor GKT137831 alleviates hypertensive cardiac hypertrophy in models of secondary hypertension; however, it remains unclear about its effect on hypertensive cardiac hypertrophy in models of essential hypertension. This study is aimed at determining the beneficial role of GKT137831 in hypertensive cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and its mechanisms of action. Treating with GKT137831 prevented cardiac hypertrophy in SHRs. Likewise, decreasing production of reactive oxygen species (ROS) with GKT137831 reduced epidermal growth factor receptor (EGFR) activity in the left ventricle of SHRs. Additionally, EGFR inhibition also reduced ROS production in the left ventricle and blunted hypertensive cardiac hypertrophy in SHRs. Moreover, inhibition of the ROS-EGFR pathway with Nox1/4 inhibitor GKT137831 or selective EGFR inhibitor AG1478 reduced protein and mRNA levels of proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β), as well as the activities of Akt and extracellular signal-regulated kinase (ERK) 1/2 in the left ventricle of SHRs. In summary, GKT137831 prevents hypertensive cardiac hypertrophy in SHRs, Nox-deprived ROS regulated EGFR activation through positive feedback in the hypertrophic myocardium, and inhibition of the ROS-EGFR pathway mediates the protective role of GKT137831 in hypertensive cardiac hypertrophy via repressing cardiac inflammation and activation of Akt and ERK1/2. This research will provide additional details for GKT137831 to prevent hypertensive cardiac hypertrophy.

中文翻译：

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ROS-EGFR途径的抑制通过抑制心脏炎症和激活Akt和ERK1 / 2介导Nox1 / 4抑制剂GKT137831对高血压性心肌肥大的保护作用。

氧化应激，炎症和高血压构成了自我延续的恶性循环，加剧了高血压和随后的高血压心脏肥大。NADPH氧化酶（Nox）1/4抑制剂GKT137831减轻继发性高血压模型中的高血压心脏肥大；然而，在原发性高血压模型中其对高血压心脏肥大的影响尚不清楚。这项研究旨在确定GKT137831在自发性高血压大鼠（SHRs）的高血压心脏肥大中的有益作用及其作用机理。用GKT137831治疗可预防SHR中的心脏肥大。同样，用GKT137831减少活性氧（ROS）的产生会降低SHRs左心室的表皮生长因子受体（EGFR）活性。另外，EGFR抑制作用还可以减少左心室的ROS生成，并减轻SHR中的高血压性心肌肥大。此外，用Nox1 / 4抑制剂GKT137831或选择性EGFR抑制剂AG1478抑制ROS-EGFR途径可降低促炎细胞因子肿瘤坏死因子的蛋白质和mRNA水平。α（TNF- α），白介素6（IL-6）和白介素1β（IL- 1β）以及左心室Akt和细胞外信号调节激酶（ERK）1/2的活性SHR。总之，GKT137831可预防SHR中的高血压性心肌肥大，NOx缺乏的ROS通过肥大性心肌中的正反馈来调节EGFR激活，并且ROS-EGFR途径的抑制通过抑制心脏炎症和激活来介导GKT137831在高血压性心肌肥大中的保护作用。 Akt和ERK1 / 2。这项研究将为GKT137831预防高血压性心脏肥大提供更多细节。