Peer Reviewed

1

Document Type

Contribution to Book

Publication Date

25-9-2019

Keywords

angiotensin pathways, angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), chymase, aldosterone, heart failure

Comments

The original book chapter is available at https://www.intechopen.com/

Abstract

Aldosterone plays an important role in the regulation of blood pressure, body fluid, and electrolyte homeostasis. Overactivation of aldosterone/mineralocorticoid receptor (MR) pathway leads to hypertension, atherosclerosis, vascular damage, heart failure, and chronic kidney disease and is involved in many other diseases associated with endothelial dysfunction, inflammation, fibrosis, and metabolic disorders. Aldosterone is a final product of the renin-angiotensin-aldosterone system (RAAS), and its production is activated by angiotensin II, while angiotensin-(1–7) negatively regulates angiotensin II-mediated aldosterone production and in some experimental models inhibits aldosterone-induced damage in target tissues. In fact, the aldosterone/mineralocorticoid receptor-dependent pathway is regulated upstream by at least two major axes of RAAS: classical axis (ACE/Ang II) and nonclassical axis (ACE2/Ang-(1–7)). The relative balance between these two axes determines aldosterone production and activity. To better understand the regulation of aldosterone activity in physiology and diseases, it is important to analyze the role of aldosterone/mineralocorticoid receptor-dependent pathways in the context of upstream angiotensin pathways as some of the recently described mechanisms of RAAS represent possible novel upstream targets to inhibit aldosterone/mineralocorticoid receptor-dependent responses. In this review, we highlight the complexity of angiotensin pathways focusing on their role in various tissues in heart failure, with particular emphasis on nonclassical pathways including protective ACE2/Ang-(1–7) axis and detrimental Ang-(1–12)/chymase/Ang II axis.

Disciplines

Medical Molecular Biology | Medical Sciences

Citation

Pérez-Gordillo FL, Jesús Pérez de Vega M, Gerona-Navarro G, Rodríguez Y, Alvarez de la Rosa D, González-Muñiz R, Martín-Martínez M. Advances in the Development of Non-steroidal Mineralocorticoid-receptor Antagonists. In: Harvey B, Jaisser F, editors. Aldosterone-Mineralocorticoid Receptor - Cell Biology to Translational Medicine: InTechOpen; 2019.

DOI Link

10.5772/intechopen.87239

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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