Premium
Ischemic injury in experimental stroke depends on angiotensin II
Author(s) -
Walther Thomas,
Olah Laszlo,
Harms Christoph,
Maul Bjoern,
Bader Michael,
Hörtnagl Heide,
Schultheiss Heinz-Peter,
Mies Günter
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0601com
Subject(s) - penumbra , angiotensin ii receptor type 1 , angiotensin ii , knockout mouse , renin–angiotensin system , ischemia , stroke (engine) , medicine , infarction , middle cerebral artery , genetically modified mouse , brain ischemia , receptor , lesion , endocrinology , transgene , cardiology , blood pressure , pathology , biology , myocardial infarction , mechanical engineering , biochemistry , engineering , gene
Since pharmacological interactions of the renin‐angiotensin system appear to alter the neurological outcome of stroke patients significantly, we examined the effect of elevated levels of angiotensin II and the role of its receptor subtype ATI in brain infarction in transgenic mice after focal cerebral ischemia. Angiotensinogen‐overexpressing and angiotensin receptor ATI knockout mice underwent 1 h or 24 h permanent middle cerebral artery occlusion (MCAO). The current study revealed a much smaller penumbra size, i.e., brain tissue at risk, in angiotensinogen‐over‐expressing animals compared with their wild‐type subgroup after 1 h MCAO, but an enlarged infarct size after 24 h. In contrast, a smaller lesion area of energy failure and a much larger penumbral area were found in AT1 knockout mice compared with wild‐type litter‐mates. Lower perfusion thresholds for ATP depletion and protein synthesis inhibition after MCAO in AT1‐deficient mice and reduced cell damage in an in vitro model using embryonic neurons of AT1 knockout mice suggest injury mechanisms independent of arterial blood pressure. Our data, therefore, demonstrate a direct correlation between brain angiotensin II and the severity of ischemic injury in experimental stroke.—Walther T., Olah, L., Harms, C., Maul, B., Bader M., Hörtnagl H., Schultheiss, H.‐P., Mies G., Ischemic injury in experimental stroke depends on angiotensin II. FASEB J. 16, 169–176 (2002)