Next Article in Journal
Evidence of the CH···O HydrogenBonding in Imidazolium-Based Ionic Liquids from Far-Infrared Spectroscopy Measurements and DFT Calculations
Next Article in Special Issue
ATP1A1 Mutant in Aldosterone-Producing Adenoma Leads to Cell Proliferation
Previous Article in Journal
Toll-Like Receptor Signaling Pathways: Novel Therapeutic Targets for Cerebrovascular Disorders
Previous Article in Special Issue
Id2 Represses Aldosterone-Stimulated Cardiac T-Type Calcium Channels Expression
Article

Aldosterone Negatively Regulates Nrf2 Activity: An Additional Mechanism Contributing to Oxidative Stress and Vascular Dysfunction by Aldosterone

1
Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, 14049-900 Ribeirao Preto, Brazil
2
Health Sciences Special Academic Unit, Federal University of Jatai, 75804-020 Jataí, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Luigi Petramala
Int. J. Mol. Sci. 2021, 22(11), 6154; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116154
Received: 14 April 2021 / Revised: 28 April 2021 / Accepted: 29 April 2021 / Published: 7 June 2021
(This article belongs to the Special Issue Role of Aldosterone Excess in Determining Cardiovascular Risk)
High levels of aldosterone (Aldo) trigger oxidative stress and vascular dysfunction independent of effects on blood pressure. We sought to determine whether Aldo disrupts Nrf2 signaling, the main transcriptional factor involved in antioxidant responses that aggravate cell injury. Thoracic aorta from male C57Bl/6J mice and cultured human endothelial cells (EA.hy926) were stimulated with Aldo (100 nM) in the presence of tiron [reactive oxygen species (ROS) scavenger, eplerenone [mineralocorticoid receptor (MR) antagonist], and L-sulforaphane (SFN; Nrf2 activator). Thoracic aortas were also isolated from mice infused with Aldo (600 μg/kg per day) for 14 days. Aldo decreased endothelium-dependent vasorelaxation and increased ROS generation, effects prevented by tiron and MR blockade. Pharmacological activation of Nrf2 with SFN abrogated Aldo-induced vascular dysfunction and ROS generation. In EA.hy926 cells, Aldo increased ROS generation, which was prevented by eplerenone, tiron, and SFN. At short times, Aldo-induced ROS generation was linked to increased Nrf2 activation. However, after three hours, Aldo decreased the nuclear accumulation of Nrf2. Increased Keap1 protein expression, but not activation of p38 MAPK, was linked to Aldo-induced reduced Nrf2 activity. Arteries from Aldo-infused mice also exhibited decreased nuclear Nrf2 and increased Keap1 expression. Our findings suggest that Aldo reduces vascular Nrf2 transcriptional activity by Keap1-dependent mechanisms, contributing to mineralocorticoid-induced vascular dysfunction. View Full-Text
Keywords: aldosterone; vascular dysfunction; oxidative stress; Nrf2 aldosterone; vascular dysfunction; oxidative stress; Nrf2
Show Figures

Figure 1

MDPI and ACS Style

Rodrigues, D.; Costa, T.J.; Silva, J.F.; Neto, J.T.d.O.; Alves, J.V.; Fedoce, A.G.; Costa, R.M.; Tostes, R.C. Aldosterone Negatively Regulates Nrf2 Activity: An Additional Mechanism Contributing to Oxidative Stress and Vascular Dysfunction by Aldosterone. Int. J. Mol. Sci. 2021, 22, 6154. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116154

AMA Style

Rodrigues D, Costa TJ, Silva JF, Neto JTdO, Alves JV, Fedoce AG, Costa RM, Tostes RC. Aldosterone Negatively Regulates Nrf2 Activity: An Additional Mechanism Contributing to Oxidative Stress and Vascular Dysfunction by Aldosterone. International Journal of Molecular Sciences. 2021; 22(11):6154. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116154

Chicago/Turabian Style

Rodrigues, Daniel, Tiago J. Costa, Josiane F. Silva, José T.d.O. Neto, Juliano V. Alves, Aline G. Fedoce, Rafael M. Costa, and Rita C. Tostes 2021. "Aldosterone Negatively Regulates Nrf2 Activity: An Additional Mechanism Contributing to Oxidative Stress and Vascular Dysfunction by Aldosterone" International Journal of Molecular Sciences 22, no. 11: 6154. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116154

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop