Intrarenal Angiotensin-Converting Enzyme: the Old and the New

Abstract

Purpose of review: The intrarenal renin-angiotensin-aldosterone system (RAS) is an independent paracrine hormonal system with an increasingly prominent role in hypertension and renal disease. Two enzyme components of this system are angiotensin-converting enzyme (ACE) and more recently discovered ACE2. The purpose of this review is to describe recent discoveries regarding the roles of intrarenal ACE and ACE2 and their interaction.

Recent findings: Renal tubular ACE contributes to salt-sensitive hypertension. Additionally, the relative expression and activity of intrarenal ACE and ACE2 are central to promoting or inhibiting different renal pathologies including renovascular hypertension, diabetic nephropathy, and renal fibrosis. Renal ACE and ACE2 represent two opposing axes within the intrarenal RAS system whose interaction determines the progression of several common disease processes. While this relationship remains complex and incompletely understood, further investigations hold the potential for creating novel approaches to treating hypertension and kidney disease.

Keywords: ACE; ACE2; Hypertension; Kidney; RAS.

Fig. 1

Diagram of the actions of intrarenal ACE and ACE2. ACE converts Ang I to Ang II which is the ligand for the AT1R and promotes pathologic processes including inflammation, fibrosis, and sodium retention. ACE2 converts Ang I to Ang(1–9) and Ang II to Ang(1–7) which is the ligand for the MasR and counteracts many of the actions of the AT1R