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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/R1526    most recent 91040.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chen, S. Articles by Chen, Y. PubMed PubMed Citation Articles by Chen, S. Articles by Chen, Y.

Articles

Ischemia-induced brain damage is enhanced in human renin and angiotensinogen double-transgenic mice

Departments of ¹Pharmacology and Toxicology, ²Emergency Medicine, and ³Neuroscience, Cell Biology, and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio; and ⁴Internal Medicine and Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa

Submitted December 22, 2008 ; accepted in final form September 14, 2009

To investigate the role of brain angiotensin II (ANG II) in the pathogenesis of injury following ischemic stroke, mice overexpressing renin and angiotensinogen (R+A+) and their wild-type control animals (R–A–) were used for experimental ischemia studies. Focal brain ischemia was induced by middle cerebral artery occlusion (MCAO). The severity of ischemic injury was determined by measuring neurological deficits and histological damage at 24 and 48 h after MCAO, respectively. To exclude the influence of blood pressure and local collateral blood flow, brain slices were used for oxygen and glucose deprivation (OGD) studies. The severity of OGD-induced damage was determined by measuring indicators of tissue swelling and cell death, the intensity of the intrinsic optical signal (IOS), and the number of propidium iodide (PI) staining cells, respectively. Results showed 1) R+A+ mice showed higher neurological deficit score (3.8 ± 0.5 and 2.5 ± 0.3 for R+A+ and R–A–, respectively, P < 0.01) and larger infarct volume (22.2 ± 1.6% and 14.1 ± 1.2% for R+A+ and R–A–, respectively, P < 0.01); 2) The R+A+ brain slices showed more severe tissue swelling and cell death in the cortex (IOS: 140 ± 6% and 114 ± 10%; PI: 139 ± 20 cells/field and 39 ± 9 cells/field for R+A+ and R–A–, respectively, P < 0.01); 3) treatment with losartan (20 µmol/l) abolished OGD-induced exaggeration of cell injury seen in R+A+ mice. The data indicate that activation of ANG II/AT₁ signaling is harmful to brain exposed to ischemia.

AT₁ receptor; mouse; losartan; middle cerebral artery