Pharmacological Activation of Nrf2 Transcriptional Factor Prevents Aldosterone-Induced Vascular Dysfunction

Pharmacological Activation of Nrf2 Transcriptional Factor Prevents Aldosterone-Induced Vascular Dysfunction

• Autor
• Daniel Rodrigues
• Co-autores
• Tiago Januário da Costa , José Teles de Oliveira Neto , Josiane Fernandes da Silva , Rafael Menezes da Costa , Rita C Tostes
• Resumo

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  Background: High levels of Aldosterone (Aldo) induces vascular oxidative stress, inflammation and fibrosis independent of its effects on blood pressure. The major regulator of antioxidant response in cells is the transcriptional factor Nrf2. Chronic conditions associated with oxidative stress generally presents dysregulation in Nrf2 signaling. Hypothesis: Considering the pro-oxidant effect of Aldo we hypothesize that exposure of vascular segments to Aldo promotes oxidative stress and vascular dysfunction via dysregulation on Nrf2 signaling. Methods: Isolated thoracic aortas from male C57BL/6J mice were treated with Aldo (100 nM) for 30 min and reactive oxygen species (ROS) generation and vascular reactivity were evaluated in presence or absence of Tiron, a ROS scavenger, Eplerenone (Eple), a mineralocorticoid receptor (MR) antagonist and L-Sulforaphane (SFN), a pharmacological Nrf2 activator. Results: Aldosterone increased ROS generation [Lucigenin - (RLU): Basal: 627.3±70.5; Aldo: 2310±185.3] and vascular contraction in concentration-effect curves to phenylephrine (PE) [Maximum Response: Vehicle: 4.3±0.3; Aldo: 8.7±0.25]. However, Aldo-induced vascular contraction were prevented by ROS scavenger [Maximum Response: Tiron: 6.98±0.20; Tiron+Aldo: 6.45±0.19] and MR antagonism [Maximum Response: Eple:8.82±0.20; Eple+Aldo:9.8±0.28]. Accordingly, ROS generation were also prevented by Tiron [Lucigenin – (RLU): Tiron:807.4±95.12; Tiron+Aldo:1054±79] and MR antagonism [Lucigenin – (RLU): Eple:784.6±115.60; Eple+Aldo:838.3±57.06]. SFN treatment before Aldo treatment were able to prevent both increases in ROS generation [Lucigenin – (RLU): SFN:1242±246.60; SFN+Aldo; 1175±103.70] and vascular contraction [Maximum Response: SFN:4.30±0.24; SFN+Aldo:3.9±0.27]. Conclusions: Taken together, these data suggest that Ado-induced vascular dysfunction might be interfering with the Nrf2 system which worsens the redox status in pathologies associated with oxidative stress including the ones with high levels of Aldo. Financial support: FAPESP, CAPES, CNPq. This study was approved by the Ethics Committee on Animal Experimentation of the Ribeirao Preto Medical School (30/2018).

   

• Palavras-chave
• aldosterone, oxidative stress, nrf2
• Modalidade
• Pôster
• Área Temática
• Estresse oxidativo