Inappropriate activity of local renin-angiotensin-aldosterone system during high salt intake: impact on the cardio-renal axis

Abstract

Although there is a general agreement on the recommendation for reduced salt intake as a public health issue, the mechanism by which high salt intake triggers pathological effects on the cardio-renal axis is not completely understood. Emerging evidence indicates that the renin-angiotensin-aldosterone system (RAAS) is the main target of high Na+ intake. An inappropriate activation of tissue RAAS may lead to hypertension and organ damage. We reviewed the impact of high salt intake on the RAAS on the cardio-renal axis highlighting the molecular pathways that leads to injury effects. We also provide an assessment of recent observational studies related to the consequences of non-osmotically active Na+ accumulation, breaking the paradigm that high salt intake necessarily increases plasma Na+ concentration promoting water retention.

Figure 1. Intra-organ activation course of the two main arms of the renin-angiotensin-aldosterone system in HSD: ACE/Ang II/AT1R and ACE2/Ang-(1-7)/MAS receptor. ACE/ACE2 ratio determines which angiotensin peptide will be mainly formed: Ang II or Ang-(1-7). During HSD intake the pathway in black (ACE/Ang II/AT1R) is exacerbated due to the local increase of its components or due to decrease of ACE2/Ang-(1-7)/MAS axis (in gray). HSD: high salt diet; ACE: angiotensin converting enzyme; ACE2: angiotensin converting enzyme 2; AGT: angiotensinogen; Ang: angiotensin; AT1R: angiotensin receptor type 1; MAS: angiotensin-(1-7) receptor; SBP: systolic blood pressure; ROS: reactive oxygen species.