S-Space College of Medicine/School of Medicine (의과대학/대학원) Neuroscience (뇌신경과학전공) Journal Papers (저널논문_뇌신경과학전공)
Blockade of AT1 receptor reduces apoptosis, inflammation, and oxidative stress in normotensive rats with intracerebral hemorrhage
- Jung, K. H.; Chu, K.; Lee, S. T.; Kim, S. J.; Song, E. C.; Kim, E. H.; Park, D. K.; Sinn, D. I.; Kim, J. M.; Kim, M.; Roh, J. K.
- Issue Date
- J Pharmacol Exp Ther. 2007 Sep;322(3):1051-8. Epub 2007 May 30.
- Angiotensin II Type 1 Receptor Blockers/*pharmacology; Animals; Apoptosis/drug effects; Benzimidazoles/administration & dosage/*pharmacology; Benzoates/administration & dosage/*pharmacology; Cerebral Hemorrhage/*drug therapy/pathology; Inflammation/drug therapy; Neuroprotective Agents/pharmacology; Nitric Oxide Synthase Type III/genetics; Oxidative Stress/drug effects; PPAR gamma/genetics; Rats; Up-Regulation/drug effects
- 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.
- 0022-3565 (Print)
- Files in This Item: There are no files associated with this item.