title: "Angiotensin II memory" contributes to the development of hypertension and vascular injury via activation of NADPH oxidase.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Laboratory Animal Sciences, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Song
authors.initials: S
authors.lastname: Lai
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Xia
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, China. Electronic address: whxdy112@ccmu.edu.cn.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, China. Electronic address: hhli1935@aliyun.com.
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology* / Q000293:injuries*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology*; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism*; D009924:Organ Culture Techniques; D057772:Vascular System Injuries / Q000139:chemically induced / Q000201:enzymology*
chemical_list: D000804:Angiotensin II; D019255:NADPH Oxidases
keywords: Angiotensin II; Free radicals; Hypertension; NADPH oxidases