Renin-angiotensin system in the kidney: What is new?

Abstract

The renin-angiotensin system (RAS) has been known for more than a century as a cascade that regulates body fluid balance and blood pressure. Angiotensin II(Ang II) has many functions in different tissues; however it is on the kidney that this peptide exerts its main functions. New enzymes, alternative routes for Ang IIformation or even active Ang II-derived peptides have now been described acting on Ang II AT1 or AT2 receptors, or in receptors which have recently been cloned, such as Mas and AT4. Another interesting observation was that old members of the RAS, such as angiotensin converting enzyme (ACE), renin and prorenin, well known by its enzymatic activity, can also activate intracellular signaling pathways, acting as an outside-in signal transduction molecule or on the renin/(Pro)renin receptor. Moreover, the endocrine RAS, now is also known to have paracrine, autocrine and intracrine action on different tissues, expressing necessary components for local Ang II formation. This in situ formation, especially in the kidney, increases Ang II levels to regulate blood pressure and renal functions. These discoveries, such as the ACE2/Ang-(1-7)/Mas axis and its antangonistic effect rather than classical deleterious Ang II effects, improves the development of new drugs for treating hypertension and cardiovascular diseases.

Keywords: Angiotensin II; Hypertension treatment; Kidney; Receptor; Renin-angiotensin system.

Figure 1

Classic view of renin-angiotensin system cascade (blue) and recent view of renin-angiotensin system cascade (green). AP: Aminopeptidase; APA: Aminopeptidase A; APN: Aminopeptidase N; CP: Carboxypeptidase; EP: Endopeptidase; ACE: Angiotensin converting enzyme; ACE2: Angiotensin converting enzyme 2; CPP: Carboxypeptidase P; PRCP: Prolyl carboxypeptidase; NEP: Neprilysin; PO: Prolyl oligopeptidase; Mas: Ang-(1-7) Mas receptor. Adaptated from Axelband et al[20] with permission.