RT Journal Article
SR Electronic
T1 Blockade of AT1 Receptor Reduces Apoptosis, Inflammation, and Oxidative Stress in Normotensive Rats with Intracerebral Hemorrhage
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1051
OP 1058
DO 10.1124/jpet.107.120097
VO 322
IS 3
A1 Keun-Hwa Jung
A1 Kon Chu
A1 Soon-Tae Lee
A1 Se-Jeong Kim
A1 Eun-Cheol Song
A1 Eun-Hee Kim
A1 Dong-Kyu Park
A1 Dong-In Sinn
A1 Jeong-Min Kim
A1 Manho Kim
A1 Jae-Kyu Roh
YR 2007
UL http://jpet.aspetjournals.org/content/322/3/1051.abstract
AB 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 γ and decrease oxidative stress, apoptotic signal, tumor necrosis factor-α, 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.