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http://hdl.handle.net/1843/61870
Type: | Artigo de Periódico |
Title: | Neuroprotection by post-stroke administration of an oral formulation of angiotensin-(1-7) in ischaemic stroke |
Authors: | Douglas M. Bennion Chad H. Jones Lauren L. Donnangelo Justin T. Graham Jacob D. Isenberg Alex N. Dang Vermali Rodriguez Rubén Dario Sinisterra Millán Frederico Barros de Sousa Robson Augusto Souza dos Santos Colin Sumners |
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 angiotensin II via its type 1 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-𝛽-cyclodextrin [HP𝛽CD–Ang-(1–7)] as an orally bioavailable treatment. In three separate protocols, HP𝛽CD–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 HP𝛽CD–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. |
Subject: | Angiotensina Enzima conversora da angiotensina Fluxo sanguíneo Acidentes vasculares cerebrais Ciclodextrinas Fisiologia experimental |
language: | eng |
metadata.dc.publisher.country: | Brasil |
Publisher: | Universidade Federal de Minas Gerais |
Publisher Initials: | UFMG |
metadata.dc.publisher.department: | ICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA ICX - DEPARTAMENTO DE QUÍMICA |
Rights: | Acesso Restrito |
metadata.dc.identifier.doi: | http://dx.doi.org/10.1113/EP086957 |
URI: | http://hdl.handle.net/1843/61870 |
Issue Date: | 2018 |
metadata.dc.url.externa: | https://physoc.onlinelibrary.wiley.com/doi/10.1113/EP086957 |
metadata.dc.relation.ispartof: | Experimental Physiology |
Appears in Collections: | Artigo de Periódico |
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