title: Anxiolytic- and antidepressant-like effects of angiotensin-(1-7) in hypertensive transgenic (mRen2)27 rats.
abstract: Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain. Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioural responses. In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depression-like behaviours observed in transgenic hypertensive (mRen2)27 rats (TGRs). We also hypothesized that Ang-(1-7) could be involved in the anxiolytic-like effect induced by ACE (angiotensin-converting enzyme) treatment in these hypertensive rats. Therefore, TGRs and Sprague-Dawley rats were subjected to the Elevated Plus Maze (EPM) test, Forced Swimming Test (FST) and Novelty Suppressed Feeding (NSF). TGRs presented a decreased percentage of entries in the open arms of the EPM test, a phenotype reversed by systemic treatment with enalapril or intracerebroventricular infusion of Ang-(1-7). It is interesting that pre-treatment with A779, a selective Mas receptor antagonist, prevented the anxiolytic-like effect induced by the ACE inhibitor. In the NSF test, TGRs showed increased latency to eating, an indicative of a higher aversion in response to a new environment. These animals also showed increased immobility in the FST. Again, Ang-(1-7) reversed this phenotype. Thus, our data showed that Ang-(1-7) can modulate anxiety- and depression-like behaviours in TGRs and warrant further investigation as a new therapy for certain psychiatric disorders.
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Almeida-Santos
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Kangussu
authors.affiliation: Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fabrício A
authors.initials: FA
authors.lastname: Moreira
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Robson A S
authors.initials: RA
authors.lastname: Santos
authors.affiliation: Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Daniele C
authors.initials: DC
authors.lastname: Aguiar
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil mjcampagnole.ufmg@gmail.com.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Campagnole-Santos
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics; D013550:Swimming
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D010446:Peptide Fragments; C562214:mRen2 protein, rat; D004656:Enalapril; D000803:Angiotensin I; D012083:Renin; C118790:angiotensin I (1-7)
keywords: ACE inhibitor; angiotensin-(1–7); anxiety; depression; transgenic hypertensive (mRen2)27 rats