“Angiotensin II memory‿contributes to the development of hypertension and vascular injury via activation of NADPH oxidase

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• 作者：Wen-Jun Li^a ; Ying Liu^c ; Jing-Jing Wang^b ; Yun-Long Zhang^c ; Song Lai^c ; Yun-Long Xia^c ; Hong-Xia Wang^a ; ^{whxdy112@ccmu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Hui-Hua Li^a ; ^{hhli1935@aliyun.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Angiotensin II ; Hypertension ; NADPH oxidases ; Free radicals
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 March 2016
• 年：2016
• 卷：149
• 期：Complete
• 页码：18-24
• 全文大小：1185 K

文摘

Activation of the rennin-angiotensin system plays a critical role in the development of hypertension and its complication. Our previous study has demonstrated that a cellular “memory” is involved in angiotensin II (Ang II)-induced cardiac hypertrophy. The aim of this study is to investigate the effect of reversal of high Ang II to normal condition on hypertension and vascular damage.

Main methods

Wild-type male mice were randomly divided into five groups. The vascular function, inflammation, oxidative stress and angiogenesis were examined by aortic ring relaxation studies, histological analysis, real-time PCR and Western blot analysis.

Key findings

We found that continuous high Ang II infusion for 3 weeks (Ang II 3w) significantly elevated blood pressure, increased aortic wall thickness, collagen deposition, inflammation, oxidative stress, vascular function and activation of p38 MAPK, JNK1/2, STAT3 and NF-κB pathways in mouse aorta compared with saline group. High Ang II exposure for 2 weeks followed by saline for 1 week (Ang II 2 + 1w) failed to reverse these alterations. This phenomenon was named “metabolic memory” (or persistent effect). However, addition of NADPH oxidase inhibitor apocynin during saline infusion (Ang II 2 + 1w + Apo) markedly ameliorated such deleterious effects.

Significance

These results showed that we report the first that persistent effect or “metabolic memory” of angiotensin II through NADPH oxidase-mediated oxidative stress plays important roles in hypertension and vascular injury.