The renin-angiotensin-aldosterone system: An old tree sprouts new shoots

The intricate physiological and pathological diversity of the Renin-Angiotensin-Aldosterone System (RAAS) underpins its role in maintaining bodily equilibrium. This paper delves into the classical axis (Renin-ACE-Ang II-AT1R axis), the protective arm (ACE2-Ang (1–7)-MasR axis), the prorenin-PRR-MAP kinases ERK1/2 axis, and the Ang IV-AT4R-IRAP cascade of RAAS, examining their functions in both physiological and pathological states. The dysregulation or hyperactivation of RAAS is intricately linked to numerous diseases, including cardiovascular disease (CVD), renal damage, metabolic disease, eye disease, Gastrointestinal disease, nervous system and reproductive system diseases. This paper explores the pathological mechanisms of RAAS in detail, highlighting its significant role in disease progression. Currently, in addition to traditional drugs like ACEI, ARB, and MRA, several novel therapeutics have emerged, such as angiotensin receptor-enkephalinase inhibitors, nonsteroidal mineralocorticoid receptor antagonists, aldosterone synthase inhibitors, aminopeptidase A inhibitors, and angiotensinogen inhibitors. These have shown potential efficacy and application prospects in various clinical trials for related diseases. Through an in-depth analysis of RAAS, this paper aims to provide crucial insights into its complex physiological and pathological mechanisms and offer valuable guidance for developing new therapeutic approaches. This comprehensive discussion is expected to advance the RAAS research field and provide innovative ideas and directions for future clinical treatment strategies.