Ischemia-induced brain damage is enhanced in human renin and angiotensinogen double-transgenic mice. Am J Physiol Regul Integr Comp Physiol 2009 Nov;297(5):R1526-31
Date
09/18/2009Pubmed ID
19759335Pubmed Central ID
PMC2777773DOI
10.1152/ajpregu.91040.2008Scopus ID
2-s2.0-70449659424 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
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 micromol/l) abolished OGD-induced exaggeration of cell injury seen in R+A+ mice. The data indicate that activation of ANG II/AT(1) signaling is harmful to brain exposed to ischemia.
Author List
Chen S, Li G, Zhang W, Wang J, Sigmund CD, Olson JE, Chen YAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin IIAngiotensin II Type 1 Receptor Blockers
Angiotensinogen
Animals
Blood Pressure
Brain
Brain Ischemia
Cell Death
Disease Models, Animal
Humans
Infarction, Middle Cerebral Artery
Losartan
Male
Mice
Mice, Transgenic
Receptor, Angiotensin, Type 1
Regional Blood Flow
Renin
Severity of Illness Index
Signal Transduction
