title: Strong reduction of low-density lipoprotein receptor/apolipoprotein E expressions by telmisartan in cerebral cortex and hippocampus of stroke resistant spontaneously hypertensive rats.
abstract: BACKGROUND
  Telmisartan is a unique angiotensin II type 1 receptor blocker with a partial peroxisome proliferator-activated receptor-γ (PPARγ) agonistic property to exert not only antihypertensive effect but also antimetabolic syndrome effect.
  
  
  METHODS
  We examined the long-term effect of telmisartan on cholesterol transport-related proteins (low-density lipoprotein receptor [LDL-R]/apolipoprotein E [ApoE]) and microtubule-associated proteins 2 (MAP2) in the brains of stroke resistant spontaneously hypertensive rats (SHR-SRs), which were divided into 3 experiment groups including vehicle group (SHR/Ve), low-dose telmisartan group (SHR/Low, .3 mg/kg/day), and high-dose telmisartan group (SHR/High, 3 mg/kg/day).
  
  
  RESULTS
  The numbers of LDL-R- and immuno-ApoE-positive neurons increased in both cerebral cortex and hippocampus of SHR/Ve throughout 6, 12, and 18 months of age, compared with age-matched normotensive Wistar rats. On the other hand, telmisartan significantly reduced the numbers of LDL-R- and ApoE immuno-positive neurons in both cerebral cortex and hippocampus, with similar effectiveness in the SHR/Low group without blood pressure (BP) lowering to BP lowering (SHR/High). The decrease of MAP2-positive neuron in SHR/Ve was recovered by telmisartan in both cerebral cortex and hippocampus.
  
  
  CONCLUSIONS
  These findings suggest that a long-term treatment with telmisartan directly improved neuronal lipid metabolism in the cerebral cortex and hippocampus of SHR-SR, mainly improving LDL-R and ApoE metabolism (SHR/Low) with a small additive benefit by BP lowering (SHR/High), which could provide a preventative approach in patients with hypertension at risk of Alzheimer disease.
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: 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: 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: Yusuke
authors.initials: Y
authors.lastname: Fukui
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Syoichiro
authors.initials: S
authors.lastname: Kono
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Wentao
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Omote
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: 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: pfvk6dyq@s.okayama-u.ac.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 / Q000096:biosynthesis* / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015140:Dementia, Vascular / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000187:drug effects*; D020521:Stroke / Q000235:genetics*; 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's disease; ApoE; LDL-R; spontaneously hypertensive rat; telmisartan