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Stroke Research and TreatmentVolume 2014 2014, Article ID 560491, 9 pages

Research Article

Charlie Norwood VA Medical Center, Augusta, GA 30912, USA

Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, HM 1212, 1120 15th Street, Augusta, GA 30912, USA

Department of Biostatistics, Georgia Regents University, Augusta, GA 30912, USA

Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA

Department of Physiology, Georgia Regents University, Augusta, GA 30912, USA

Department of Neurology, Georgia Regents University, Augusta, GA 30912, USA

Received 19 March 2014; Revised 23 June 2014; Accepted 7 July 2014; Published 24 July 2014

Academic Editor: Mohammad Moshahid Khan

Copyright © 2014 Tauheed Ishrat et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background and Purpose. Oxidative stress and matrix metalloproteinase MMP activity have been identified as key mediators of early vascular damage after ischemic stroke. Somewhat surprisingly, the angiotensin II type 1 receptor AT1 blocker, candesartan, has been shown to acutely increase MMP activity while providing neurovascular protection. We aimed to determine the contribution of MMP and nitrative stress to the effects of angiotensin blockade in experimental stroke. Methods. Wistar rats n = 9–14-group; a total of 99 were treated in a factorial design with candesartan 1 mg-kg IV, alone or in combination with either a peroxynitrite decomposition catalyst, FeTPPs, 30 mg-kg IP or GM6001 50 mg-kg IP MMP inhibitor. Neurological deficit, infarct, size and hemorrhagic transformation HT were measured after 3 h of middle cerebral artery occlusion MCAO and 21 h of reperfusion. MMP activity and nitrotyrosine expression were also measured. Results. Candesartan reduced infarct size and HT when administered alone and in combination with FeTPPs . GM6001 did not significantly affect HT when administered alone, but the combination with candesartan caused increased HT and worsened neurologic score . Conclusions. Acute administration of candesartan reduces injury after stroke despite increasing MMP activity, likely by an antioxidant mechanism.





Autor: Tauheed Ishrat, Anna Kozak, Ahmed Alhusban, Bindu Pillai, Maribeth H. Johnson, Azza B. El-Remessy, Adviye Ergul, and Susan

Fuente: https://www.hindawi.com/



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