期刊
JOURNAL OF CARDIOLOGY
卷 60, 期 5-6, 页码 489-494出版社
ELSEVIER
DOI: 10.1016/j.jjcc.2012.08.004
关键词
Hypertension; Cognitive function; Brain; Angiotensin receptor blocker
资金
- Japan Society for the Promotion of Science [22790709]
- Kimura Memorial Foundation Research Grant
Background and purpose: Cognitive decline may occur as a result of hypertension, and is dependent on the function of hippocampus. Brain-derived neurotrophic factor (BDNF) mediated by angiotensin II-induced oxidative stress protects against cell death in hippocampus. Angiotensin II receptor blacker (ARB), candesartan, activates BDNF in the hippocampus. Furthermore, peroxisome proliferator-activatecl receptor (PPAR)-gamma activation in the brain prevents brain damage. Telmisartan, a unique ARB with PPARgamma stimulating activity, protects against cognitive decline partly because of PPAR-gamma activation. The aim of the present study was to determine whether telmisartan protects against cognitive decline via up-regulation of BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of hypertensive rats, partly because of PPAR-gamma activation. Methods and results: We divided stroke-prone spontaneously hypertensive rats (SFIRSPs), as hypertensive and vascular dementia model rats, into five groups, telmisartan-treated (TLM), TLM + GW9662, a PPAR-gamma inhibitor, -treated (T + G), GW9662-treated (GW),TLM + ANA-12, a TrkB antagonist, -treated (T + A), and vehicle-treated SHRSPs (VEH). After the treatment for 28 days, systolic blood pressure did not change in all groups. However, BDNF expression in the hippocampus was significantly higher in TLM than in VEH to a greater extent than in T + G. Cognitive performance was significantly higher in TLM than in VEH to a greater extent than in T + G, and was not different between T + A, GW, and VEH. Conclusion: Telmisartan protects against cognitive decline via up-regulation of BDNF/TrkB in the hippocampus of SHRSPs, partly because of PPAR-gamma activation independent of blood pressure-lowering effect. (C) 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
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