Neuroprotection by post-stroke administration of an oral formulation of angiotensin-(1-7) in ischaemic stroke
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Universidade Federal de Minas Gerais
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Artigo de periódico
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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.
Abstract
Assunto
Angiotensina, Enzima conversora da angiotensina, Fluxo sanguíneo, Acidentes vasculares cerebrais, Ciclodextrinas, Fisiologia experimental
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Angiotensin-(1-7), Angiotensin-converting enzyme 2, Cerebral blood flow, Ischaemic stroke, Neuroprotection
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https://physoc.onlinelibrary.wiley.com/doi/10.1113/EP086957