Open AccessDetrimental Effects of Centrally Administered Angiotensin II are Enhanced in a Mouse Model of Alzheimer Disease Independently of Blood Pressure
Author(s) -
Takane Koki,
Hasegawa Yu,
Lin Bowen,
Koibuchi Nobutaka,
Cao Cheng,
Yokoo Takashi,
KimMitsuyama Shokei
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.004897
Subject(s) - angiotensin ii , medicine , endocrinology , oxidative stress , renin–angiotensin system , cerebral amyloid angiopathy , alzheimer's disease , angiotensin receptor , atrophy , blood pressure , disease , dementia
Background The significance of brain angiotensin II in Alzheimer disease ( AD ) is unclear. Methods and Results To examine the role of brain angiotensin II in AD , intracerebroventricular angiotensin II infusion was performed on 5 XFAD mice, a mouse model of AD , and wild‐type mice, and the detrimental effects of brain angiotensin II was compared between the 2 strains of mice. Intracerebroventricular angiotensin II infusion significantly impaired cognitive function in 5 XFAD mice but not in wild‐type mice. This vulnerability of 5 XFAD mice to brain angiotensin II was associated with enhancement of hippocampal inflammation and oxidative stress and with increased cerebrovascular amyloid β deposition. We also compared the effect of brain angiotensin II on the heart and skeletal muscle between the 2 strains because AD is associated with heart failure and sarcopenia. We found that cardiac compensatory response of 5 XFAD mice to brain angiotensin II –induced hypertension was less than that of wild‐type mice. Brain angiotensin II caused skeletal muscle atrophy and injury in 5 XFAD mice more than in wild‐type mice. Conclusions Brain angiotensin II seems to be involved in cognitive impairment and brain injury in AD , which is associated with oxidative stress, inflammation, and cerebral amyloid angiopathy. Further, brain angiotensin II may participate in cardiac disease and sarcopenia observed in AD .