title: Effect of Long-Term Treatment with Fimasartan on Transient Focal Ischemia in Rat Brain.
abstract: Fimasartan is a newly developed angiotensin receptor blocker, which may have protective effects during myocardial infarction or atherosclerosis. In this context, we investigated the effects of long-term treatment with low-dose fimasartan on focal ischemia in rat brain. We induced focal ischemia in brain by transient intraluminal occlusion of middle cerebral artery (MCA) and administered low-dose (0.5 mg/kg) or regular doses (1 or 3 mg/kg) of fimasartan via intravenous routes. After the administration of low-dose (0.5 mg/kg) fimasartan, blood pressure did not decrease compared to the phosphate-buffered saline- (PBS-) control with MCA occlusion (MCAO) group. The infarct volume and ischemic cell death were reduced in the low-dose fimasartan-treated group (46 ± 41 mm(3) for 0.5 mg/kg and 153 ± 47 mm(3) for PBS-control with MCAO; P < 0.01) but not in the regular-dose groups. Low-dose fimasartan treatment improved functional recovery after ischemia and significantly decreased mortality. In our study, fimasartan reduced the degradation of IκB and the formation of an inflammatory end-product, COX-2. As a result, the recruitment of inflammatory cells in the peri-infarct area decreased in fimasartan-treated group. We have demonstrated that long-term, low-dose fimasartan treatment improved outcomes after focal ischemia in the brain via a reduction of inflammation.
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea ; Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea ; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03087, Republic of Korea.
authors.forename: Chi Kyung
authors.initials: CK
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea ; Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea ; Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.
authors.forename: Young-Ju
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea ; Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.
authors.forename: In-Young
authors.initials: IY
authors.lastname: Choi
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea.
authors.forename: Han-Gil
authors.initials: HG
authors.lastname: Jeong
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea.
authors.forename: Hong-Kyun
authors.initials: HK
authors.lastname: Park
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea.
authors.forename: Dohoung
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea.
authors.forename: Tae Jung
authors.initials: TJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea ; Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.
authors.forename: Hyunduk
authors.initials: H
authors.lastname: Jang
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea ; Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Ko
authors.affiliation: Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea ; Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea ; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03087, Republic of Korea.
authors.forename: Byung-Woo
authors.initials: BW
authors.lastname: Yoon
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D001713:Biphenyl Compounds; D016328:NF-kappa B; D011743:Pyrimidines; D013777:Tetrazoles; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C558933:fimasartan