Expression of angiotensin II AT2 receptor in the acute phase of stroke in rats

Y Z Zhu1, G N Chimon, Y C Zhu

  • 1Department of Pharmacology, Faculty of Medicine, National University of Singapore, Crescent, Singapore.

Neuroreport
|May 19, 2000
PubMed

Insights

Stroke (middle cerebral artery occlusion; MCAO) in rats showed increased angiotensin II (Ang II) receptor subtype 2 (AT2) gene expression in the infarct cortex. This suggests AT2 receptor up-regulation may play a role in stroke-related tissue repair and apoptosis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • Stroke, particularly ischemic stroke caused by middle cerebral artery occlusion (MCAO), is a leading cause of death and disability worldwide.
  • The renin-angiotensin system (RAS) and its components, including angiotensin II (Ang II) and its receptors, are implicated in various physiological and pathological processes, including cardiovascular and cerebrovascular diseases.
  • The role of specific Angiotensin II receptor subtypes, such as AT2, in the post-stroke environment remains incompletely understood.

Purpose of the Study:

  • To investigate the gene expression profile of the angiotensin II receptor subtype 2 (AT2) in a rat model of ischemic stroke.
  • To determine the temporal and spatial changes in AT2 receptor expression within the infarct core and surrounding tissue following middle cerebral artery occlusion (MCAO).
  • To explore the potential association between AT2 receptor up-regulation and cellular processes like apoptosis in the context of stroke-induced brain injury.

Main Methods:

  • Establishment of a male Wistar rat model subjected to permanent middle cerebral artery occlusion (MCAO) to induce ischemic stroke.
  • Quantitative analysis of AT2 receptor gene expression using reverse transcription polymerase chain reaction (RT-PCR) at different time points post-MCAO.
  • Localization and assessment of AT2 receptor protein expression via immunohistochemical staining in the affected cerebral cortex.
  • Detection of apoptotic markers in the necrotic areas of the stroke-affected brain tissue.

Main Results:

  • A significant up-regulation of AT2 receptor gene expression was observed in the infarct cortex, with a 2.7-fold increase at 1 day and a 1.7-fold increase at 3 days post-MCAO.
  • Immunohistochemical staining confirmed the presence of AT2 receptors within the infarct area of the cerebral cortex.
  • Apoptotic markers were detected in the necrotic cerebral cortex tissue 1 day after MCAO, coinciding with elevated AT2 receptor expression.

Conclusions:

  • The findings demonstrate a marked increase in AT2 receptor gene and protein expression in the cerebral cortex following experimental stroke (MCAO).
  • The up-regulation of the AT2 receptor in the infarct zone suggests its potential involvement in the cellular responses, including apoptosis, during the tissue repair process after stroke.
  • Further research is warranted to elucidate the precise mechanisms by which AT2 receptor modulation influences stroke outcomes and to explore its therapeutic potential.