Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 843-848 |
| Number of pages | 6 |
| Journal | Circulation |
| Volume | 110 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 17-08-2004 |
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All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
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Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation. / Iwai, Masaru; Liu, Hong Wei; Chen, Rui; Ide, Ayumi; Okamoto, Shoko; Hata, Ryuji; Sakanaka, Masahiro; Shiuchi, Tetsuya; Horiuchi, Masatsugu.
In: Circulation, Vol. 110, No. 7, 17.08.2004, p. 843-848.Research output: Contribution to journal › Article
TY - JOUR
T1 - Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation
AU - Iwai, Masaru
AU - Liu, Hong Wei
AU - Chen, Rui
AU - Ide, Ayumi
AU - Okamoto, Shoko
AU - Hata, Ryuji
AU - Sakanaka, Masahiro
AU - Shiuchi, Tetsuya
AU - Horiuchi, Masatsugu
PY - 2004/8/17
Y1 - 2004/8/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=4143095706&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4143095706&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.0000138848.58269.80
DO - 10.1161/01.CIR.0000138848.58269.80
M3 - Article
C2 - 15289370
AN - SCOPUS:4143095706
VL - 110
SP - 843
EP - 848
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 7
ER -