title: Telmisartan ameliorates inflammatory responses in SHR-SR after tMCAO.
abstract: Telmisartan, an angiotensin receptor blocker with high lipid solubility, also called metabo-sartan, not only reduces blood pressure (BP), but also ameliorates inflammation in the cerebral cortex and in adipose tissue. We examined the effects of telmisartan on inflammatory responses of monocyte chemotactic protein-1, tumor necrosis factor-α, and ionized calcium-binding adapter molecule 1 in the brain of spontaneously hypertensive rat stroke-resistant (SHR-SR) after transient middle cerebral artery occlusion (tMCAO). At 12 weeks of age, SHR-SR received tMCAO for 90 minutes and were divided into 3 groups, that is, the vehicle group, a low-dose telmisartan group (.3 mg/kg/day), and a high-dose telmisartan group (3 mg/kg/day). Immunohistological analysis was performed when rats became 6, 12 and 18 months old. Monocyte chemotactic protein-1, tumor necrosis factor-α, and ionized calcium-binding adapter molecule 1 cells (/mm(2)) immunoreactivities increased with age in the cerebral cortex and hippocampus of the vehicle group, suggesting strong and persistent inflammatory changes in SHR-SR after tMCAO up to 18 months of age. On the other hand, a low dose of telmisartan significantly reduced such inflammatory changes without lowering BP, whereas a high dose of telmisartan showed a few additional improvements, including the lowering of BP throughout 6-18 months of age. The present study suggests that persistent hypertension after tMCAO caused a long-lasting inflammatory response in the SHR-SR brain, and that even a low dose of telmisartan reduced continuous inflammation without lowering BP via its pleiotropic effects in the SHR-SR brain. A high dose of telmisartan had a few additional benefits, including lowering BP.
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: 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: 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: kosatou@cc.okayama-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000367:Age Factors; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology; D006973:Hypertension / Q000188:drug therapy*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology*; D000077333:Telmisartan; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D002135:Calcium-Binding Proteins; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D008840:Microfilament Proteins; D014409:Tumor Necrosis Factor-alpha; D000077333:Telmisartan
keywords: Iba-1; MCP-1; Spontaneously hypertensive rat; TNF-α; inflammatory response; telmisartan