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Updated: May 2, 2026
Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
Published on: June 7, 2016
Possible inhibition of focal cerebral ischemia by angiotensin II type 2 receptor stimulation
Masaru Iwai1, Hong-Wei Liu, Rui Chen
1Department of Medical Biochemistry, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 791-0295, Japan.
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 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.
Insights
Angiotensin II type 2 receptor stimulation protects against ischemic brain lesions by modulating cerebral blood flow and superoxide production. Deficiency in this receptor exacerbates stroke damage.
Area of Science:
- Neuroscience
- Cardiovascular Research
- Pharmacology
Background:
- Investigating the role of angiotensin II receptor subtypes in focal brain ischemia.
- Middle cerebral artery (MCA) occlusion is a common model for inducing focal brain ischemia.
Purpose of the Study:
- To determine the protective role of the angiotensin II type 2 receptor (AT2R) in focal brain ischemia.
- To elucidate the mechanisms underlying AT2R-mediated protection.
Main Methods:
- Utilizing wild-type (Agtr2+) and AT2R-deficient (Agtr2-) mice subjected to MCA occlusion.
- Assessing ischemic area, neurological deficits, cerebral blood flow, and superoxide production.
- Administering an AT1 receptor blocker (valsartan) to evaluate its effects.
Main Results:
- AT2R deficiency significantly increased ischemic area, neurological deficit, and reduced cerebral blood flow post-MCA occlusion.
- Superoxide production and NADPH oxidase activity were elevated in the ischemic brains of Agtr2- mice.
- Valsartan demonstrated protective effects in wild-type mice, which were diminished in Agtr2- mice.
Conclusions:
- AT2 receptor stimulation confers a protective effect against ischemic brain lesions.
- This protection is partly mediated by the modulation of cerebral blood flow and superoxide production.
- Targeting AT2R may represent a therapeutic strategy for ischemic stroke.
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