Tratamento com aceturato de diminazeno ou angiotensina-(1-7) em ratas hipertensas gestantes atenua disfunções cardiovasculares na prole
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2019-04-22
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Universidade Federal de Goiás
Resumo
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.
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BESSA, A. S. M. Tratamento com aceturato de diminazeno ou angiotensina-(1-7) em ratas hipertensas gestantes atenua disfunções cardiovasculares na prole. 2019. 93 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2019.