Journal article
The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke
Neuropharmacology, Vol.81, pp.134-141
06/01/2014
DOI: 10.1016/j.neuropharm.2014.01.044
PMCID: PMC7472595
PMID: 24508710
Abstract
Evidence indicates that angiotensin II type 2 receptors (AT2R) exert cerebroprotective actions during stroke. A selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exert beneficial effects in models of cardiac and renal disease, as well as hemorrhagic stroke. Here, we hypothesize that C21 may exert beneficial effects against cerebral damage and neurological deficits produced by ischemic stroke. We determined the effects of central and peripheral administration of C21 on the cerebral damage and neurological deficits in rats elicited by endothelin-1 induced middle cerebral artery occlusion (MCAO), a model of cerebral ischemia. Rats infused centrally (intracerebroventricular) with C21 before endothelin-1 induced MCAO exhibited significant reductions in cerebral infarct size and the neurological deficits produced by cerebral ischemia. Similar cerebroprotection was obtained in rats injected systemically (intraperitoneal) with C21 either before or after endothelin-1 induced MCAO. The protective effects of C21 were reversed by central administration of an AT2R inhibitor, PD123319. While C21 did not alter cerebral blood flow at the doses used here, peripheral post-stroke administration of this agent significantly attenuated the MCAO-induced increases in inducible nitric oxide synthase, chemokine (C-C) motif ligand 2 and C-C chemokine receptor type 2 mRNAs in the cerebral cortex, indicating that the cerebroprotective action is associated with an anti-inflammatory effect. These results strengthen the view that AT2R agonists may have potential therapeutic value in ischemic stroke, and provide the first evidence of cerebroprotection induced by systemic post stroke administration of a selective AT2R agonist. (c) 2014 Elsevier Ltd. All rights reserved.
Details
- Title: Subtitle
- The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke
- Creators
- Jason P. Joseph - University of FloridaAdam P. Mecca - University of FloridaRobert W. Regenhardt - University of FloridaDouglas M. Bennion - University of FloridaVermali Rodriguez - University of FloridaFiona Desland - University of FloridaNeal A. Patel - University of FloridaDavid J. Pioquinto - University of FloridaThomas Unger - Maastricht UniversityMichael J. Katovich - University of FloridaU. Muscha Steckelings - University of Southern DenmarkColin Sumners - University of Florida
- Resource Type
- Journal article
- Publication Details
- Neuropharmacology, Vol.81, pp.134-141
- DOI
- 10.1016/j.neuropharm.2014.01.044
- PMID
- 24508710
- PMCID
- PMC7472595
- NLM abbreviation
- Neuropharmacology
- ISSN
- 0028-3908
- eISSN
- 1873-7064
- Publisher
- Elsevier
- Number of pages
- 8
- Grant note
- 12PRE11940010 / American Heart Association Greater Southeast Pre-doctoral Fellowship; American Heart Association University of Florida University Scholar Program 09GRNT2060421 / American Heart Association Greater Southeast Affiliate; American Heart Association American Medical Association University of Florida HHMI Science for Life program T32 HL-083810 / University of Florida Multidisciplinary Training Program in Hypertension University of Florida Clinical and Translational Science Institute
- Language
- English
- Date published
- 06/01/2014
- Academic Unit
- Otolaryngology
- Record Identifier
- 9984962530902771
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