Aims: 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 3weeks (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 2weeks followed by saline for 1week (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.
Keywords: Angiotensin II; Free radicals; Hypertension; NADPH oxidases.
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