title: Strong improvement of apolipoprotein E/low-density lipoprotein receptor signals by telmisartan in poststroke spontaneously hypertensive stroke resistant.
abstract: BACKGROUND
  Telmisartan, an angiotensin receptor blocker also called metabosartan, is a promising solution for preventing cognitive decline or the incidence of dementia.
  
  
  METHODS
  We examined the effects of telmisartan on cholesterol transport-related proteins (apolipoprotein E [ApoE]/low-density lipoprotein receptor [LDL-R]) and microtubule-associated protein 2 (MAP2) in the brain of spontaneously hypertensive stroke resistant (SHR-SR). SHR-SR received transient middle cerebral artery occlusion (tMCAO) for 90 minutes at 12 weeks of age and then was divided into 3 experiment groups including a vehicle, low-dose telmisartan (.3 mg/kg/day), and high-dose telmisartan (3 mg/kg/day).
  
  
  RESULTS
  The low dose served to improve the metabolic syndrome of SHR-SR without lowering the blood pressure (BP) whereas the high dose was used to improve metabolic syndrome while lowering BP. Immunohistologic analysis showed that ApoE expression of cortical neurons was strong in the vehicle group at 6, 12, and 18 months of age, and that this ApoE expression pattern was very similar between the ipsilateral and contralateral sides of cerebral ischemia. On the other hand, LDL-R expression of cortical neurons was transiently increased at 6 months of age only on the ipsilateral side. Telmisartan dramatically suppressed the expression of ApoE/LDL-R at both doses. There was no remarkable difference in neuronal MAP2 staining between the 3 groups.
  
  
  CONCLUSIONS
  These findings suggest that both low and high doses of telmisartan prevented the activation of ApoE/LDL-R in SHR-SR after tMCAO, and that the antimetabolic effect was regarded as the most important mechanism with few additional benefits by lowering BP in this transient stroke model.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Hishikawa
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Morimoto
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohta
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Deguchi
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address: tooy@d1.dion.ne.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011973:Receptors, LDL / Q000187:drug effects*; D015427:Reperfusion Injury / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D020521:Stroke / Q000503:physiopathology; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001057:Apolipoproteins E; D001562:Benzimidazoles; D001565:Benzoates; D011973:Receptors, LDL; D019950:Mitogen-Activated Protein Kinase 1; D000077333:Telmisartan
keywords: Alzheimer disease; ApoE; LDL-R; spontaneously hypertensive rat; telmisartan