The Important Role of Systemic and Local Renin- Angiotensin System

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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.