Mas receptor contributes to pregnancy-induced cardiac remodelling.
Previous studies have demonstrated a protective effect of the Ang-(1-7)/Mas receptor axis on pathological cardiac hypertrophy. Also, the involvement of Mas receptor in exercise-induced cardiac hypertrophy has been suggested. However, the role of the Ang-(1-7)/Mas receptor on pregnancy-induced cardiac remodelling remains unknown. The objective of the present study was to evaluate the participation of the Mas receptor in the development of the cardiac hypertrophy and fibrosis induced by gestation. Female Wistar rats were divided in three groups: control, pregnant and pregnant treated with Mas receptor antagonist A-779. Wild-type (WT) and Mas-knockout (KO) mice were distributed in non-pregnant and pregnant groups. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography. The medial part of the left ventricle (LV) was collected for histological analysis. Echocardiographic analysis was used to evaluate cardiac function. SBP was not changed by pregnancy or A-779 treatment in the Wistar rats. Pharmacological blockade or genetic deletion of Mas receptor attenuates the pregnancy-induced myocyte hypertrophy. The treatment with A-779 or genetic deletion of the Mas receptor increased the collagen III deposition in LV from pregnant animals without changing fibroblast proliferation. KO mice presented a lower ejection fraction (EF), fractional shortening (FS) and stroke volume (SV) and higher end systolic volume (ESV) compared with WT. Interestingly, pregnancy restored these parameters. In conclusion, these data show that although Mas receptor blockade or deletion decreases physiological hypertrophy of pregnancy, it is associated with more extracellular matrix deposition. These alterations are associated with improvement of cardiac function through a Mas-independent mechanism.
Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil.
Cintia
C
do Carmo E Silva
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil.
Jônathas Fernandes Queiroz
JFQ
de Almeida
Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil.
Larissa Matuda
LM
Macedo
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil.
Marcos Barrouin
MB
Melo
Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil.
Gustavo Rodrigues
GR
Pedrino
Department of Histology, Embryology and Cell Biology, Federal University of Goiás, Goiânia 74001-970, Brazil.
Fernanda Cristina Alcantara
FCA
Dos Santos
Department of Histology, Embryology and Cell Biology, Federal University of Goiás, Goiânia 74001-970, Brazil.
Manoel Francisco
MF
Biancardi
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil.|National Institute of Science and Technology in Nanobiopharmaceutics, Belo Horizonte 31270-901, Brazil.
Robson Augusto Souza
RAS
Dos Santos
Department of Pharmacology, Federal University of Goi s, Goiânia 74001-970, Brazil.
Adryano Augustto Valladão
AAV
de Carvalho
Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil.
Elizabeth Pereira
EP
Mendes
Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil.
Diego Basile
DB
Colugnati
Department of Pharmacology, Federal University of Goi s, Goiânia 74001-970, Brazil.
Renata
R
Mazaro-Costa
Department of Physiological Sciences, Federal University of Goiás, Goiânia 74001-970, Brazil castro@ufg.br.|National Institute of Science and Technology in Nanobiopharmaceutics, Belo Horizonte 31270-901, Brazil.
Carlos Henrique
CH
de Castro
A-779; Angiotensin-(1–7); cardiac hypertrophy; fibrosis; heart function