Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation.
BACKGROUND
The role of angiotensin II receptor subtypes was investigated in focal brain ischemia induced by middle cerebral artery (MCA) occlusion.


RESULTS
In Agtr2+ (wild-type) mice, MCA occlusion induced focal ischemia of approximately 20% to 30% of the total area in coronal section of the brain. The ischemic area was significantly larger in angiotensin II type 2 receptor-deficient (Agtr2-) mice than in Agtr2+ mice. The neurological deficit after MCA occlusion was also greater in Agtr2- mice than in Agtr2+ mice. The decrease in surface cerebral blood flow after MCA occlusion was significantly exaggerated in the peripheral region of the MCA territory in Agtr2- mice. Superoxide production and NADPH oxidase activity were enhanced in the ischemic area of the brain in Agtr2- mice. An AT1 receptor blocker, valsartan, at a nonhypotensive dose significantly inhibited the ischemic area, neurological deficit, and reduction of cerebral blood flow as well as superoxide production and NADPH oxidase activity in Agtr2+ mice. These inhibitory actions of valsartan were weaker in Agtr2- mice.


CONCLUSIONS
These results suggest that AT2 receptor stimulation has a protective effect on ischemic brain lesions, at least partly through the modulation of cerebral blood flow and superoxide production.
Iwai
Masaru
M
Department of Medical Biochemistry, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 791-0295, Japan.
Liu
Hong-Wei
HW
Chen
Rui
R
Ide
Ayumi
A
Okamoto
Shoko
S
Hata
Ryuji
R
Sakanaka
Masahiro
M
Shiuchi
Tetsuya
T
Horiuchi
Masatsugu
M
D000804:Angiotensin II / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy*; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D013481:Superoxides; D000804:Angiotensin II; D000068756:Valsartan; D019255:NADPH Oxidases; D014633:Valine