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

• Autor(a) principal: Bessa, Amanda de Sá Martins de
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/00130000044jh
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/9954
• topic: Sistema renina-angiotensina; Programação fetal; Hipertensão; Remodelamento cardíaco; Angiotensin-(1-7); ACE2; Diminazene aceturate; Cardiac remodeling; CIENCIAS BIOLOGICAS

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.