Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation

Masaru Iwai, Hong Wei Liu, Rui Chen, Ayumi Ide, Shoko Okamoto, Ryuji Hata, Masahiro Sakanaka, Tetsuya Shiuchi, Masatsugu Horiuchi

Research output: Contribution to journalArticle

205 Citations (Scopus)

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 languageEnglish
Pages (from-to)843-848
Number of pages6
JournalCirculation
Volume110
Issue number7
DOIs
Publication statusPublished - 17-08-2004

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Angiotensin Type 2 Receptor
Brain Ischemia
Cerebrovascular Circulation
Middle Cerebral Artery Infarction
Valsartan
Superoxides
NADPH Oxidase
Brain
Angiotensin Receptors
Middle Cerebral Artery
Ischemia

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Iwai, Masaru ; Liu, Hong Wei ; Chen, Rui ; Ide, Ayumi ; Okamoto, Shoko ; Hata, Ryuji ; Sakanaka, Masahiro ; Shiuchi, Tetsuya ; Horiuchi, Masatsugu. / Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation. In: Circulation. 2004 ; Vol. 110, No. 7. pp. 843-848.
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title = "Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation",
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.",
author = "Masaru Iwai and Liu, {Hong Wei} and Rui Chen and Ayumi Ide and Shoko Okamoto and Ryuji Hata and Masahiro Sakanaka and Tetsuya Shiuchi and Masatsugu Horiuchi",
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Iwai, M, Liu, HW, Chen, R, Ide, A, Okamoto, S, Hata, R, Sakanaka, M, Shiuchi, T & Horiuchi, M 2004, 'Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation', Circulation, vol. 110, no. 7, pp. 843-848. https://doi.org/10.1161/01.CIR.0000138848.58269.80

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 journalArticle

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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.

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