title: Cardioprotective effects of diminazene aceturate in pressure-overloaded rat hearts.
abstract: OBJECTIVE
  Angiotensin-converting enzyme 2 (ACE2) is a key modulator of the renin-angiotensin system. Recent studies have shown that diminazene aceturate (DIZE) acts as an ACE2 activator. The aim of this study was to evaluate the cardiac effects of chronic treatment with DIZE in pressure-overloaded rats.
  
  
  METHODS
  Male Wistar rats were divided into 4 groups: (1) sham; (2) aortic banded rats (AB); (3) AB+DIZE (1mg/kg, gavage); and (4) AB+DIZE+A-779 (120μg/day, osmotic mini-pumps). Cardiac hypertrophy was evaluated by ventricular mass index and myocyte cross-sectional area. mRNA expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and transforming growth factor beta 1 (TGF-β) was quantified by RT-PCR. Cardiac function was assessed according to the Langendorff technique. The ACE2 and Mas protein expression was examined by western blot analysis.
  
  
  RESULTS
  DIZE treatment prevented the cardiomyocyte hypertrophy promoted by AB and A-779 inhibited this effect. Also, DIZE induced the expression of ANP and BNP mRNA in cardiac tissue from AB rats and attenuated the impairment in left ventricular end-systolic pressure and left ventricular developed pressure, +dP/dt and -dP/dt caused by AB. These effects were blocked by A-779. Moreover, DIZE prevented the increase in the expression of TGF-β mRNA in AB hearts, but it did not change the ACE2 and Mas protein expression.
  
  
  CONCLUSIONS
  These results showed that DIZE was efficient in preventing the cardiomyocyte hypertrophy and attenuated the left ventricular contractile impairment induced by pressure overload. However, further studies are necessary to confirm whether these effects were due to ACE2 activation.
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil.
authors.forename: Larissa Matuda
authors.initials: LM
authors.lastname: Macedo
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil.
authors.forename: Álvaro Paulo da Silva
authors.initials: ÁP
authors.lastname: Souza
authors.affiliation: Department of Morphology, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil.
authors.forename: Marilda Luz de Andrade
authors.initials: ML
authors.lastname: De Maria
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Goiás, Goiânia 74001-970, Brazil.
authors.forename: Clayton Luiz
authors.initials: CL
authors.lastname: Borges
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Goiás, Goiânia 74001-970, Brazil.
authors.forename: Célia Maria de Almeida
authors.initials: CM
authors.lastname: Soares
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil.
authors.forename: Gustavo Rodrigues
authors.initials: GR
authors.lastname: Pedrino
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil.
authors.forename: Diego Basile
authors.initials: DB
authors.lastname: Colugnati
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; National Institute of Science and Technology in Nanobiopharmaceutics, 31270-901, Brazil.
authors.forename: Robson Augusto Souza Dos
authors.initials: RA
authors.lastname: Santos
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil; National Institute of Science and Technology in Nanobiopharmaceutics, 31270-901, Brazil.
authors.forename: Elizabeth Pereira
authors.initials: EP
authors.lastname: Mendes
authors.affiliation: Department of Morphology, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; National Institute of Science and Technology in Nanobiopharmaceutics, 31270-901, Brazil.
authors.forename: Anderson José
authors.initials: AJ
authors.lastname: Ferreira
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil; National Institute of Science and Technology in Nanobiopharmaceutics, 31270-901, Brazil. Electronic address: castro@ufg.br.
authors.forename: Carlos Henrique de
authors.initials: CH
authors.lastname: Castro
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004133:Diminazene / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; C003915:diminazene aceturate; D004133:Diminazene
keywords: ACE2 activation; Angiotensin-(1–7); Angiotensin-converting enzyme 2; Cardiac function; Cardiac hypertrophy; Diminazene aceturate