Journal article
Neuroprotection by post-stroke administration of an oral formulation of angiotensin-(1-7) in ischaemic stroke
Experimental physiology, Vol.103(6), pp.916-923
06/01/2018
DOI: 10.1113/EP086957
PMID: 29663576
Abstract
As a target for stroke therapies, the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas [ACE2/Ang-(1-7)/Mas] axis of the renin-angiotensin system can be activated chronically to induce neuroprotective effects, in opposition to the deleterious effects of angiotensinII via its type1 receptor. However, more clinically relevant treatment protocols with Ang-(1-7) that involve its systemic administration beginning after the onset of ischaemia have not been tested. In this study, we tested systemic post-stroke treatments using a molecule where Ang-(1-7) is included within hydroxypropyl--cyclodextrin [HPCD-Ang-(1-7)] as an orally bioavailable treatment. In three separate protocols, HPCD-Ang-(1-7) was administered orally to Sprague-Dawley rats after induction of ischaemic stroke by endothelin-1-induced middle cerebral artery occlusion: (i) to assess its effects on cerebral damage and behavioural deficits; (ii) to determine its effects on cardiovascular parameters; and (iii) to determine whether it altered cerebral blood flow. The results indicate that post-stroke oral administration of HPCD-Ang-(1-7) resulted in 25% reductions in cerebral infarct volumes and improvement in neurological functions (P<0.05), without inducing any alterations in blood pressure, heart rate or cerebral blood flow. In conclusion, Ang-(1-7) treatment using an oral formulation after the onset of ischaemia induces significant neuroprotection in stroke and might represent a viable approach for taking advantage of the protective ACE2/Ang-(1-7)/Mas axis in this disease.
Details
- Title: Subtitle
- Neuroprotection by post-stroke administration of an oral formulation of angiotensin-(1-7) in ischaemic stroke
- Creators
- Douglas M. Bennion - University of FloridaChad H. Jones - University of FloridaLauren L. Donnangelo - University of FloridaJustin T. Graham - University of FloridaJacob D. Isenberg - University of FloridaAlex N. Dang - University of FloridaVermali Rodriguez - University of FloridaRuben D. M. Sinisterra - Universidade Federal de Minas GeraisFrederico B. Sousa - Univ Fed Itajuba, Inst Chem & Phys, Itajuba, MG, BrazilRobson A. S. Santos - Universidade Federal de Minas GeraisColin Sumners - University of Florida
- Resource Type
- Journal article
- Publication Details
- Experimental physiology, Vol.103(6), pp.916-923
- DOI
- 10.1113/EP086957
- PMID
- 29663576
- NLM abbreviation
- Exp Physiol
- ISSN
- 0958-0670
- eISSN
- 1469-445X
- Publisher
- Wiley
- Number of pages
- 8
- Grant note
- 2T32HL083810-06A1 / National Heart Lung and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 12PRE11940010 / American Heart Association
- Language
- English
- Date published
- 06/01/2018
- Academic Unit
- Otolaryngology
- Record Identifier
- 9984962627602771
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