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: Keun-Hwa Jung, Kon Chu, Soon-Tae Lee, Se-Jeong Kim, Eun-Cheol Song, Eun-Hee Kim, Dong-Kyu Park, Dong-In Sinn, Jeong-Min Kim, Manho Kim, Jae-Kyu Roh
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 322 Issue 3 Pg. 1051-8 (Sep 2007) ISSN: 0022-3565 [Print] United States
• PMID: 17538008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Benzoates
• Neuroprotective Agents
• PPAR gamma
• Nitric Oxide Synthase Type III
• Telmisartan

Topics

• 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
• Telmisartan
• Up-Regulation (drug effects)