Larissa Matuda Macedo1, Álvaro Paulo da Silva Souza1, Marilda Luz de Andrade De Maria2, Clayton Luiz Borges3, Célia Maria de Almeida Soares3, Gustavo Rodrigues Pedrino1, Diego Basile Colugnati1, Robson Augusto Souza Dos Santos4, Elizabeth Pereira Mendes5, Anderson José Ferreira6, Carlos Henrique de Castro7. 1. Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil. 2. Department of Morphology, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil. 3. Department of Biochemistry and Molecular Biology, Federal University of Goiás, Goiânia 74001-970, Brazil. 4. 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. 5. Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil; National Institute of Science and Technology in Nanobiopharmaceutics, 31270-901, Brazil. 6. Department of Morphology, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil; National Institute of Science and Technology in Nanobiopharmaceutics, 31270-901, Brazil. 7. 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.
Abstract
AIMS: 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. MAIN 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIMS: 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. MAIN 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. KEY FINDINGS: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. SIGNIFICANCE: 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: Rosiane F Brito; Aldi F S França; Aline P Pansani; Carlos H Castro; Diego B Colugnati; Luciano F Souza; Luiza A Rabelo; Valéria Nunes-Souza; Carlos H Xavier; Graciele A Oliveira; Daniel S Corrêa; Adriano T Ramos; Larissa M Macedo; Reginaldo N Ferreira Journal: J Anim Sci Date: 2021-06-01 Impact factor: 3.159
Authors: Amanda S M Bessa; Érika F Jesus; Allancer D C Nunes; Carolina N R Pontes; Ismaley S Lacerda; Jaqueline M Costa; Elisângela J Souza; Ruy S Lino-Júnior; Manoel F Biancardi; Fernanda C A Dos Santos; Gustavo R Pedrino; Diego B Colugnati; Renata Mazaro-Costa; Elizabeth P Mendes; Carlos H Castro Journal: Hypertens Res Date: 2019-09-10 Impact factor: 3.872