Temporary pretreatment with the angiotensin II type 1 receptor blocker, valsartan, prevents ischemic brain damage through an increase in capillary density.
OBJECTIVE
We investigated the effect of temporary treatment with a nonhypotensive dose of valsartan on ischemic brain damage in C57BL/6 mice.


METHODS
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 (-, -).


RESULTS
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.


CONCLUSIONS
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.
Li
Jian-Mei
JM
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, Japan.
Mogi
Masaki
M
Iwanami
Jun
J
Min
Li-Juan
LJ
Tsukuda
Kana
K
Sakata
Akiko
A
Fujita
Teppei
T
Iwai
Masaru
M
Horiuchi
Masatsugu
M
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000517:prevention & control*; D002196:Capillaries / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D004249:DNA Damage; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry*; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D013481:Superoxides; D000068756:Valsartan; D014633:Valine