Temporary Pretreatment With the Angiotensin II Type 1 Receptor Blocker, Valsartan, Prevents Ischemic Brain Damage Through an Increase in Capillary Density

• Published in: Stroke (1970) 2008-07, Vol.39 (7), p.2029-2036
• Main Authors: LI, Jian-Mei, MOGI, Masaki, IWANAMI, Jun, MIN, Li-Juan, TSUKUDA, Kana, SAKATA, Akiko, FUJITA, Teppei, IWAI, Masaru, HORIUCHI, Masatsugu
• Format: Article
• Language: English
• Subjects: Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Antihypertensive agents; Biological and medical sciences; Brain - drug effects; Brain - pathology; Brain Injuries - prevention & control; Brain Ischemia - drug therapy; Brain Ischemia - prevention & control; Capillaries - drug effects; Cardiovascular system; Chemokine CCL2 - metabolism; DNA Damage; Infarction, Middle Cerebral Artery - drug therapy; Medical sciences; Mice; Mice, Inbred C57BL; Neurology; Oxidative Stress; Pharmacology. Drug treatments; Receptor, Angiotensin, Type 1 - chemistry; Superoxides - metabolism; Tetrazoles - pharmacology; Valine - analogs & derivatives; Valine - pharmacology; Valsartan; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.107.503458

We investigated the effect of temporary treatment with a nonhypotensive dose of valsartan on ischemic brain damage in C57BL/6 mice. We separated the mice into 3 groups of valsartan treatment before middle cerebral artery (MCA) occlusion: (1) for 4 weeks: Val (2W, 2W); (2) for 2 weeks followed by its cessation for 2 weeks: Val (2W, -); and (3) no treatment for 4 weeks: Val (-, -). Ischemic volume, DNA damage, superoxide production, and mRNA levels of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha on the ipsilateral side after 24 hours of MCA occlusion were significantly reduced in both Val (2W, 2W) and Val (2W, -) mice compared with those in Val (-, -) mice, whereas these parameters were larger in Val (2W, -) mice than in Val (2W, 2W) mice. Moreover, mice in both the Val (2W, 2W) and Val (2W, -) groups exhibited an increase in cerebral blood flow in the peripheral territory of the MCA 1 hour after MCA occlusion, with increases in endothelial nitric oxide synthase activation and nitric oxide production. Before MCA occlusion, treatment with valsartan did not influence superoxide production or mRNA levels of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha in the brain. However, the capillary density in the brain in both Val (2W, 2W) and Val (2W, -) mice was increased before MCA occlusion. Our results suggest that temporary valsartan treatment could protect against ischemic brain damage even after its cessation, at least in part due to an increase in capillary density.