Journal
JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
Volume 23, Issue 6, Pages 1545-1553Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jstrokecerebrovasdis.2013.12.052
Keywords
Stroke-resistant spontaneously hypertensive rat; telmisartan; oxidative stress; phosphorylated alpha-synuclein; peroxisome proliferator-activated receptor gamma
Categories
Funding
- Ministry of Education, Science, Culture, and Sports of Japan [21390267]
- Research Committee of CNS Degenerative Diseases
- Ministry of Health, Labour, and Welfare of Japan
Ask authors/readers for more resources
Previously, we reported that reactive oxygen species and signaling molecules of angiotensin II produced lipid peroxides, degenerated proteins, and injured DNA after cerebral ischemia in normotensive Wistar rats. Here, we investigated the long-term effect of the angiotensin II type I receptor blocker telmisartan on oxidative stress and hyperphosphorylated alpha-synuclein accumulation in stroke-resistant spontaneously hypertensive rats (SHR-SR). At the age of 3 months, SHR-SR were divided into 3 treatment groups: SHR-SR vehicle (SHR/Ve), SHR-SR low-dose telmisartan (.3 mg/kg/day) (SHR/low), and SHR-SR high-dose telmisartan (3 mg/kg/day) (SHR/high). Immunohistologic analyses were conducted in these groups and Wistar rats at the age of 6, 12, and 18 months. The SHR/Ve group demonstrated more progressive increase in advanced glycation end product (AGE)-, 4-hydroxy-2-nonenal (4-HNE)-, and phosphorylated alpha-synuclein (pSyn)-positive cells in the cerebral cortex and hippocampus compared with the Wistar group at 18 months. These expressions were reduced in the SHR/low group even without lowering blood pressure (BP), and expressions were dramatically suppressed in the SHR/high group with lowering of BP. These data suggest that persistent hypertension in SHR-SR strongly potentiate the markers of oxidative damage (AGEs and 4-HNE) and abnormal accumulation of pSyn, which were greatly suppressed by telmisartan in a dose-dependent manner without and with lowering of BP. (C) 2014 by National Stroke Association
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available