Telmisartan Reduces Progressive Oxidative Stress and Phosphorylated α-Synuclein Accumulation in Stroke-resistant Spontaneously Hypertensive Rats after Transient Middle Cerebral Artery Occlusion

• Published in: Journal of stroke and cerebrovascular diseases Vol. 23; no. 6; pp. 1554 - 1563
• Main Authors: Sato, Kota, MD, Yamashita, Toru, MD, PhD, Kurata, Tomoko, MD, PhD, Lukic, Violeta, MD, PhD, Fukui, Yusuke, BS, Hishikawa, Nozomi, MD, PhD, Deguchi, Kentaro, MD, PhD, Abe, Koji, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2014
• Subjects: Aldehydes - metabolism; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Animals; Benzimidazoles - pharmacology; Benzimidazoles - therapeutic use; Benzoates - pharmacology; Benzoates - therapeutic use; Blood Pressure - drug effects; Brain - drug effects; Brain - metabolism; Cardiovascular; Glycation End Products, Advanced - metabolism; Hypertension - metabolism; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Male; Neurology; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; oxidative stress; Oxidative Stress - drug effects; Parkinson's disease; phosphorylated α-synuclein; Phosphorylation - drug effects; Rats; Rats, Inbred SHR; Rats, Wistar; Spontaneously hypertensive rat; Synucleins - metabolism; telmisartan; Spontaneously hypertensive rat; Parkinson's disease; telmisartan; phosphorylated α-synuclein; oxidative stress
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2013.12.051

Telmisartan is an angiotensin receptor blocker with high lipid solubility, also called metabosartan, which exerts a special protective effect on both acute brain damage and chronic neurodegeneration. We examined the effects of telmisartan on oxidative stress by advanced glycation end product (AGE) and 4-hydroxynonenal (4-HNE) assays and the accumulation of phosphorylated α-synuclein (pSyn) in the brain of stroke-resistant spontaneously hypertensive rats (SHR-SR). At the age of 12 weeks, SHR-SR received transient middle cerebral artery occlusion (tMCAO) for 90 minutes and were divided into the following 3 groups: the vehicle group, the low-dose telmisartan group (.3 mg/kg/day), and the high-dose telmisartan group (3 mg/kg/day, postoperatively). Immunohistologic analysis was performed when rats were 6, 12, and 18 months old. AGE, 4-HNE, and pSyn–positive cells (per square millimeter) increased with age in the cerebral cortex and hippocampus of the vehicle group, in the low-dose telmisartan group, these parameters decreased without lowering blood pressure (BP), and in the high-dose telmisartan group, these parameters increased with lowering BP. The present study suggests that a persistent hypertension after tMCAO caused a progressive oxidative stress with the abnormal accumulation of pSyn, and that telmisartan reduced oxidative stress and the accumulation of pSyn without lowering BP (low dose) or improved these conditions with a reduction in BP (high dose) via its pleiotropic effects through a potential peroxisome proliferator–activated receptor gamma stimulation in the brain of SHR-SR.