Aldosterone/MR Signaling, Oxidative Stress, and Vascular Dysfunction
The mineralocorticoid receptor (MR) is a transcription factor of the family of steroid receptors that classically binds the hormone aldosterone. The contribution of MR in the regulation of sodium retention and blood pressure is well known. However, MR is expressed in extrarenal tissues including endothelial and vascular smooth muscle cells, and its activation leads to vascular remodeling, vascular stiffness, and endothelial dysfunction leading to vascular damage, an important pathophysiological process in hypertension and other cardiovascular diseases. Moreover, MR is expressed in nonvascular cells in close contact with the vascular wall including immune cells and adipocytes that might influence vascular function and structure. MR activation involves its translocation to the nucleus and regulation of gene transcription. In addition, aldosterone exerts rapid non-genomic effects mediated by MR-dependent and MR-independent mechanisms. Both genomic and non-genomic effects facilitate reactive oxygen species (ROS) production (particularly by the enzyme NADPH oxidase), inflammation, and fibrosis, which, in turn, promote tissue remodeling, vascular stiffening, and endothelial dysfunction. Studies with MR antagonists and experimental models with cell-specific knockout or overexpression of MR further support a role for aldosterone/MR-mediated oxidative stress-dependent processes in vascular damage. This review focuses on the relationship between aldosterone/MR signaling and oxidative stress and the implications in vascular regulation in health and disease.
CommentsThe original book chapter is available at https://www.intechopen.com/ Part of the ‘Aldosterone-Mineralocorticoid Receptor: Cell Biology to Translational Medicine’ collection: https://repository.rcsi.com/account/home#/collections/4974911
Published CitationBriones AM, Touyz RM. Aldosterone/MR Signaling, Oxidative Stress, and Vascular Dysfunction. In: Harvey B, Jaisser F, editors. Aldosterone-Mineralocorticoid Receptor - Cell Biology to Translational Medicine: InTechOpen; 2019.
- Molecular Medicine