title: Blockade of AT1 receptor reduces apoptosis, inflammation, and oxidative stress in normotensive rats with intracerebral hemorrhage.
abstract: Angiotensin II exerts its central nervous system effects primarily via its receptors AT1 and AT2, and it participates in the pathogenesis of ischemia via AT1. The selective AT1 receptor blocker (ARB) is used in the hypertension treatment, and it exerts a variety of pleiotropic effects, including antioxidative, antiapoptotic, and anti-inflammatory effects. In this study, we investigated the therapeutic effect of the ARB telmisartan in experimental intracerebral hemorrhage (ICH) in normotensive rats. ICH was induced via the collagenase infusion or autologous blood injection. Either telmisartan at 30 mg/kg/dose or phosphate-buffered saline was orally administered 2 h after ICH induction. We evaluated hemorrhage volume, brain water content, and functional recovery, and we performed the histological analysis for terminal deoxynucleotidyl transferase dUTP nick-end labeling, leukocyte infiltration, and microglia activation. A variety of intracellular signals, in terms of oxidative stress, apoptotic molecules, and inflammatory mediators, were also measured. Telmisartan reduced hemorrhage volume, brain edema, and inflammatory or apoptotic cells in the perihematomal area. Telmisartan was noted to induce the expression of endothelial nitric-oxide synthase and peroxisome proliferator-activated receptor gamma and decrease oxidative stress, apoptotic signal, tumor necrosis factor-alpha, and cyclooxygenase-2 expression. The telmisartan-treated rats exhibited less pronounced neurological deficits and recovered better. Thus, telmisartan seems to offer neural protection, including antiapoptosis, anti-inflammatory, and antioxidant benefits in the intracerebral hemorrhage rat model.
authors.affiliation: Stroke and Neural Stem Cell Laboratory, Department of Neurology, Clinical Research Institute, Seoul National University Hospital, 28, Yongon-Dong, Chongro-Gu, Seoul, 110-744, Republic of Korea.
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Se-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Song
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Park
authors.forename: Dong-In
authors.initials: DI
authors.lastname: Sinn
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000235:genetics; D051381:Rats; D000077333:Telmisartan; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D018696:Neuroprotective Agents; D047495:PPAR gamma; D052250:Nitric Oxide Synthase Type III; D000077333:Telmisartan