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
α-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 α-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.
Key Words
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Article info
Publication history
Published online: March 31, 2014
Accepted:
December 25,
2013
Received in revised form:
December 23,
2013
Received:
November 22,
2013
Footnotes
This work was partly supported by Grant-in-Aid for Scientific Research (B) 21390267 from the Ministry of Education, Science, Culture, and Sports of Japan, Grants-in-Aid from the Research Committee of CNS Degenerative Diseases (I. Nakano), and grants (H. Mizusawa, M. Nishizawa, H.Sasaki, G. Sobue) from the Ministry of Health, Labour, and Welfare of Japan.
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.052
Copyright
© 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
