Tratamento com aceturato de diminazeno ou angiotensina-(1-7) em ratas hipertensas gestantes atenua disfunções cardiovasculares na prole

• Ano de defesa: 2019
• Autor(a) principal: Bessa, Amanda de Sá Martins de
• Orientador(a): Castro, Carlos Henrique de
• Banca de defesa: Castro, Carlos Henrique de, Costa, Renata Mazaro, Fonseca, Silvia Carolina Guatimosim
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Programa de Pós-graduação em Ciências Biológicas (ICB)
• Departamento: Instituto de Ciências Biológicas - ICB (RG)
• País: Brasil
• Palavras-chave em Português: Sistema renina-angiotensina; Programação fetal; Hipertensão; Remodelamento cardíaco
• Palavras-chave em Inglês: Angiotensin-(1-7); ACE2; Diminazene aceturate; Cardiac remodeling
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/9954

It has been proven that harmful stimuli during gestation can promote deleterious outcomes in offspring. Furthermore, previous studies have observed that the Renin-angiotensin system (RAS) can play a role in this pathological process. TheACE2/Ang-(1-7)/Mas axis presents several protective actions in the cardiovascular system. Thus, the aim of this study was to investigate whether the treatment with diminazene aceturate (DIZE), a putative ACE2 activator, or with Angiotensin-(1-7) during the pregnancy could attenuate the development of cardiovascular dysfunctions in the adult offspring of spontaneously hypertensive rats (SHR). For this, pregnant SHR received DIZE or Ang-(1-7) during the gestation. The SBP was measured in the male offspring by tail-cuff plethysmography. Thereafter, the left ventricular contractile function and coronary reactivity were evaluated by the Langendorff technique. Aortic vascular reactivity was also evaluated by isolated vessel in an organ bath. Samples of the LV were collected for histology and Western blot assay. Maternal treatment with DIZE (SHR: 181 ± 2.03 vs. SHR DIZE: 166.6 ± 0.35 mmHg, P <0.05) or Ang-(1-7) (SHR: 167.3 ± 1.79 vs. SHR Ang-(1-7): 153.8 ± 1.75 mmHg, P <0.05) during pregnancy attenuated the increase of the SBP in adult offspring. Additionally, the treatments reduced the cardiomyocyte diameter (SHR: 16.3 ± 0.11 vs. SHR DIZE: 12.9 ± 0.95 μm, P <0.05) (SHR: 16.6 ± 0.12 vs. SHR Ang-(1-7): 14 ± 0.10 μm, P <0.05) and degradation of the extracellular matrix (SHR: 15.6 ± 0.96 vs. SHR DIZE: 9.0 ± 0.61%, P <0.05) (SHR: 17.2 ± 1.27 vs. SHR Ang- (1-7): 10.3 ± 0,73%, P <0.05) in LV. The maternal treatment with DIZE and Ang-(1-7) improved the coronary vasodilation induced by bradykinin in isolated hearts. The expressions of AT1, Mas, ACE, ACE2, ERK Total, P-ERK, TNF-α, Collagen I, SOD, and Catalase in LV were not modified with Ang-(1-7), but this treatment decreased the AT2 (SHR: 0.90 ± 0.03 vs. SHR Ang- (1-7): 0.74 ± 0.05, P <0.05) expression. These data show that the treatment with DIZE or Ang-(1-7) during gestation promoted beneficial effects in attenuating hypertension and cardiac remodeling in adult offspring.