title: Activation of angiotensin-(1-7)/Mas axis in the brain lowers blood pressure and attenuates cardiac remodeling in hypertensive transgenic (mRen2)27 rats.
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.affiliation: Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Kangussu
authors.affiliation: Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Priscila S
authors.initials: PS
authors.lastname: Guimaraes
authors.affiliation: Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Nadu
authors.affiliation: Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Marcos B
authors.initials: MB
authors.lastname: Melo
authors.affiliation: Laboratory of Hypertension, Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Robson A S
authors.initials: RA
authors.lastname: Santos
authors.affiliation: 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.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Campagnole-Santos
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009206:Myocardium / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
chemical_list: C092006:7-Ala-angiotensin (1-7); D000959:Antihypertensive Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: (mRen2)27 rats; Angiotensin-(1–7); Anti-hypertensive; Autonomic nervous system; Cardiac remodeling; Mas receptor