Published online before print August 2, 2004, doi: 10.1161/01.CIR.0000138848.58269.80
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(Circulation. 2004;110:843-848.)
© 2004 American Heart Association, Inc.
Original Articles |
Possible Inhibition of Focal Cerebral Ischemia by Angiotensin II Type 2 Receptor Stimulation
From the Departments of Medical Biochemistry (M.I., H.-W.L., R.C., A.I., S.O., T.S., M.H.) and Anatomy (R.H., M.S.), Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime, Japan.
Correspondence to Masatsugu Horiuchi, MD, PhD, Department of Medical Biochemistry, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 791-0295, Japan. E-mail horiuchi{at}m.ehime-u.ac.jp
Received September 9, 2003; de novo received January 27, 2004; revision received April 1, 2004; accepted April 4, 2004.
Background— The role of angiotensin II receptor subtypes was investigated in focal brain ischemia induced by middle cerebral artery (MCA) occlusion.
Methods and Results— In Agtr2+ (wild-type) mice, MCA occlusion induced focal ischemia of 
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.
Key Words: stroke • angiotensin • ischemia • receptors • stress
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