Renin-Angiotensin System: Updated Understanding and Role in Physiological and Pathophysiological States

Abstract

The classical view of the renin-angiotensin system (RAS) is that of the circulating hormone pathway involved in salt and water homeostasis and blood pressure regulation. It is also involved in the pathogenesis of cardiac and renal disorders. This led to the creation of drugs blocking the actions of this classical pathway, which improved cardiac and renal outcomes. Our understanding of the RAS has significantly expanded with the discovery of new peptides involved in this complex pathway. Over the last two decades, a counterregulatory or protective pathway has been discovered that opposes the effects of the classical pathway. Components of RAS are also implicated in the pathogenesis of obesity and its metabolic diseases. The continued discovery of newer molecules also provides novel therapeutic targets to improve disease outcomes. This article aims to provide an overview of an updated understanding of the RAS, its role in physiological and pathological processes, and potential novel therapeutic options from RAS for managing cardiorenal disorders, obesity, and related metabolic disorders.

Renin–Angiotensin–Aldosterone System: From History to Practice of a Secular Topic

“…This local RAAS may work independently or together with the circulating RAAS and has both pathogenic and protective pathways. In particular, the latter ones provide even more potential targets for new medications that may stimulate the protective pathways and therefore have an inhibiting effect on the RAAS [79,80]. Some limits of the available phase 3 clinical studies on novel RAAS inhibitors need to be pointed out to open possible new perspectives and inspire future investigations.…”

The Senescent Heart—“Age Doth Wither Its Infinite Variety”

“…Ang II, as the effector peptide of the renin-angiotensin system (RAS), activates a number of intracellular signal transduction pathways via the AT1 receptor [193]. Apart from the circulating/systemic RAS cascade, the identification of a localised RAS in the heart with all components required for Ang II synthesis has unravelled the crucial role of this system in cardiac growth and development [194,195]. Interestingly, fibroblasts are the major RAS-positive cells in the heart, with very high AT1 receptor density.…”