| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, Germany;
* Department of Cardiology and Pneumology, Free University of Berlin; and
Institute of Pharmacology and Toxicology, Medical Faculty (Charité) of the Humboldt University, Germany
2Correspondence: University Hospital Benjamin Franklin, Department of Cardiology and Pneumology, Free University of Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany. E-mail: thomas.walther{at}ukbf.fu-berlin.de
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 AT1 in brain infarction in transgenic mice after focal cerebral ischemia. Angiotensinogen-overexpressing and angiotensin receptor AT1 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-overexpressing 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 littermates. 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.
Key Words: A II • focal cerebral ischemia • transgenic mice • penumbra • collateral flow
This article has been cited by other articles:
|
|
 |
|
  J.-M. Li, M. Mogi, J. Iwanami, L.-J. Min, K. Tsukuda, A. Sakata, T. Fujita, M. Iwai, and M. Horiuchi Temporary Pretreatment With the Angiotensin II Type 1 Receptor Blocker, Valsartan, Prevents Ischemic Brain Damage Through an Increase in Capillary Density Stroke, July 1, 2008; 39(7): 2029 - 2036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ay, E. M. Arsava, J. Rosand, K. L. Furie, A. B. Singhal, P. W. Schaefer, O. Wu, R. G. Gonzalez, W. J. Koroshetz, and A. G. Sorensen Severity of Leukoaraiosis and Susceptibility to Infarct Growth in Acute Stroke Stroke, May 1, 2008; 39(5): 1409 - 1413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-H. Jung, K. Chu, S.-T. Lee, S.-J. Kim, E.-C. Song, E.-H. Kim, D.-K. Park, D.-I. Sinn, J.-M. Kim, M. Kim, et al. Blockade of AT1 Receptor Reduces Apoptosis, Inflammation, and Oxidative Stress in Normotensive Rats with Intracerebral Hemorrhage J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 1051 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ishikawa, E. Sekizuka, N. Yamaguchi, H. Nakadate, S. Terao, D. N. Granger, and H. Minamitani Angiotensin II type 1 receptor signaling contributes to platelet-leukocyte-endothelial cell interactions in the cerebral microvasculature Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2306 - H2315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Munzenmaier and A. S. Greene Chronic angiotensin II AT1 receptor blockade increases cerebral cortical microvessel density Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H512 - H516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Iwai, H.-W. Liu, R. Chen, A. Ide, S. Okamoto, R. Hata, M. Sakanaka, T. Shiuchi, and M. Horiuchi Possible Inhibition of Focal Cerebral Ischemia by Angiotensin II Type 2 Receptor Stimulation Circulation, August 17, 2004; 110(7): 843 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Kusaka, G. Kusaka, C. Zhou, M. Ishikawa, A. Nanda, D. N. Granger, J. H. Zhang, and J. Tang Role of AT1 receptors and NAD(P)H oxidase in diabetes-aggravated ischemic brain injury Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2442 - H2451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Delles, G. Michelson, J. Harazny, S. Oehmer, K. F. Hilgers, and R. E. Schmieder Impaired Endothelial Function of the Retinal Vasculature in Hypertensive Patients Stroke, June 1, 2004; 35(6): 1289 - 1293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Didion and F. M. Faraci Angiotensin II Produces Superoxide-Mediated Impairment of Endothelial Function in Cerebral Arterioles Stroke, August 1, 2003; 34(8): 2038 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Gerzanich, S. Ivanova, H. Zhou, and J. M. Simard Mislocalization of eNOS and Upregulation of Cerebral Vascular Ca2+ Channel Activity in Angiotensin-Hypertension Hypertension, May 1, 2003; 41(5): 1124 - 1130. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
