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.
Mas receptor contributes to pregnancy-induced cardiac remodelling
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Cintia do Carmo e Silva, Jônathas Fernandes Queiroz de Almeida, Larissa Matuda Macedo, Marcos Barrouin Melo, Gustavo Rodrigues Pedrino, Fernanda Cristina Alcantara dos Santos, Manoel Francisco Biancardi, Robson Augusto Souza dos Santos, Adryano Augustto Valladão de Carvalho, Elizabeth Pereira Mendes, Diego Basile Colugnati, Renata Mazaro-Costa, Carlos Henrique de Castro; Mas receptor contributes to pregnancy-induced cardiac remodelling. Clin Sci (Lond) 1 December 2016; 130 (24): 2305–2316. doi: https://doi.org/10.1042/CS20160095
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