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Activation of angiotensin-(1-7)/Mas axis in the brain lowers blood pressure and attenuates cardiac remodeling in hypertensive transgenic (mRen2)27 rats.
Neuropharmacology. 2015 Oct; 97:58-66.N

Abstract

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/AT1 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 μg/h) or 0.9% sterile saline (0.5 μl/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-β 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.

Authors+Show Affiliations

Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: mjcampagnole.ufmg@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25983274

Citation

Kangussu, Lucas M., et al. "Activation of angiotensin-(1-7)/Mas Axis in the Brain Lowers Blood Pressure and Attenuates Cardiac Remodeling in Hypertensive Transgenic (mRen2)27 Rats." Neuropharmacology, vol. 97, 2015, pp. 58-66.
Kangussu LM, Guimaraes PS, Nadu AP, et al. Activation of angiotensin-(1-7)/Mas axis in the brain lowers blood pressure and attenuates cardiac remodeling in hypertensive transgenic (mRen2)27 rats. Neuropharmacology. 2015;97:58-66.
Kangussu, L. M., Guimaraes, P. S., Nadu, A. P., Melo, M. B., Santos, R. A., & Campagnole-Santos, M. J. (2015). Activation of angiotensin-(1-7)/Mas axis in the brain lowers blood pressure and attenuates cardiac remodeling in hypertensive transgenic (mRen2)27 rats. Neuropharmacology, 97, 58-66. https://doi.org/10.1016/j.neuropharm.2015.04.036
Kangussu LM, et al. Activation of angiotensin-(1-7)/Mas Axis in the Brain Lowers Blood Pressure and Attenuates Cardiac Remodeling in Hypertensive Transgenic (mRen2)27 Rats. Neuropharmacology. 2015;97:58-66. PubMed PMID: 25983274.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of angiotensin-(1-7)/Mas axis in the brain lowers blood pressure and attenuates cardiac remodeling in hypertensive transgenic (mRen2)27 rats. AU - Kangussu,Lucas M, AU - Guimaraes,Priscila S, AU - Nadu,Ana Paula, AU - Melo,Marcos B, AU - Santos,Robson A S, AU - Campagnole-Santos,Maria Jose, Y1 - 2015/05/15/ PY - 2015/02/01/received PY - 2015/04/20/revised PY - 2015/04/30/accepted PY - 2015/5/19/entrez PY - 2015/5/20/pubmed PY - 2016/5/11/medline KW - (mRen2)27 rats KW - Angiotensin-(1–7) KW - Anti-hypertensive KW - Autonomic nervous system KW - Cardiac remodeling KW - Mas receptor SP - 58 EP - 66 JF - Neuropharmacology JO - Neuropharmacology VL - 97 N2 - 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/AT1 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 μg/h) or 0.9% sterile saline (0.5 μl/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-β 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. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/25983274/Activation_of_angiotensin__1_7_/Mas_axis_in_the_brain_lowers_blood_pressure_and_attenuates_cardiac_remodeling_in_hypertensive_transgenic__mRen2_27_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(15)00166-5 DB - PRIME DP - Unbound Medicine ER -