The Important Role of Systemic and Local Renin- Angiotensin System
Pp. 15-44 (30)
Danielle Sanches Aragão, Lilian Saemi Arita, Rodrigo Yokota, Lilian dos Santos, Larissa Emi Matsumoto, Marie Doki Nogueira, Fernanda Aparecida Ronchi and Danielle Yuri Arita
Knowledge of renin-angiotensin system (RAS) has evolved through the
years from the classical endocrine system view, which explains the homeostasis and
arterial blood pressure control, to a more complex system, including new components
and independent local RAS acting intracellularly and within different organs. It is wellknown
that the circulating RAS plays a physiological and important role in blood
pressure regulation through direct effects on vascular smooth muscle, aldosterone
secretion and sodium, potassium and water equilibrium. The potent vasopressor peptide
Angiotensin (Ang) II is the key regulator of the system and the Ang 1-7 counterregulates
Ang II actions. Components are generated in liver (angiotensinogen), kidneys
[renin] and vascular endothelial cell membranes (angiotensin I -converting enzyme)
and secreted to the circulation to generate systemic Ang II. Recently, the focus of
interest in the RAS changed the role of tissue/local system in specific tissue. Ang II
synthesis within tissues from angiotensinogen and enzymes is defined as local RAS.
The activation of the circulating and/or local RAS plays a fundamental role in the
pathogenesis of hypertension and chronic kidney disease. RAS blockade with
angiotensin I-converting enzyme (ACE) inhibitors or Ang II receptor blockers is a
major approach to treat cardiovascular and renal diseases. However, it is still unclear if
a dual blockade exerts a better protection than single blockade or shows a higher risk
for renal complications and hyperkalemia.
ACE inhibitors, Angiotensinogen, Angiotensins, Angiotensin
converting enzyme 2, Angiotensin I-converting enzyme, Angiotensin II-receptor
blockers, Cardiac diseases, Cells, Chronic kidney diseases, Heart, Kidney, Local
RAS, RAS blockade, Renin, Renin-angiotensin system, Systemic RAS.
Nephrology Division, Medicine Department, Escola Paulista de Medicina, Universidade Federal de São Paulo, Sao Paulo, Brazil.