Journal
NEUROPHARMACOLOGY
Volume 97, Issue -, Pages 58-66Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2015.04.036
Keywords
Angiotensin-(1-7); Mas receptor; (mRen2)27 rats; Anti-hypertensive; Cardiac remodeling; Autonomic nervous system
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Funding
- Conselho Nacional de Ciencia e Tecnologia (CNPq)
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) [PRONEX-CBB-APQ-04758-10]
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) through INCT-NanoBiofar
- CAPES
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Activation of the peripheral angiotensin-(1-7)/Mas axis of the renin-angiotensin system produces important cardioprotective actions, counterbalancing the deleterious actions of an overactivity of Ang II/AT(1) axis. In the present study we evaluated whether the chronic increase in Ang-(1-7) levels in the brain could ameliorate cardiac disorders observed in transgenic (mRen2)27 hypertensive rats through actions on Mas receptor. Sprague Dawley (SD) and transgenic (mRen2)27 hypertensive rats, instrumented with telemetry probe for arterial pressure (AP) measurement were subjected to 14 days of ICV infusion of Ang-(1-7) (200 ng/h) or Ang-(1-7) associated with Mas receptor antagonist (A779, 1 mu g/h) or 0.9% sterile saline (0.5 mu l/h) through osmotic mini-pumps. Ang-(1-7) infusion in (mRen2)27 rats reduced blood pressure, normalized the baroreflex control of HR, restored cardiac autonomic balance, reduced cardiac hypertrophy and pre-fibrotic alterations and decreased the altered imbalance of Ang II/Ang-(1-7) in the heart. In addition, there was an attenuation of the increased levels of atrial natriuretic peptide, brain natriuretic peptide, collagen I, fibronectin and TGF-beta in the heart of (mRen2)27 rats. Furthermore, most of these effects were mediated in the brain by Mas receptor, since were blocked by its selective antagonist, A779. These data indicate that increasing Ang-(1-7) levels in the brain can attenuate cardiovascular disorders observed in (mRen2)27 hypertensive rats, probably by improving the autonomic balance to the heart due to centrally-mediated actions on Mas receptor. (C) 2015 Elsevier Ltd. All rights reserved.
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