Update on the Renin- Angiotensin System

The physiological and pathophysiological actions of the renin-angiotensin system (RAS) extend far beyond its role as a regulator of cardiovascular homeostasis. The “classical” RAS has evolved into a complex system with multiple pathways and counterbalancing axes which are pivotal to the function of most organ systems in the body. The discovery of “local” RAS’s which began with the characterization of a brain RAS now includes a diverse array of tissues: liver, kidney, heart, lungs, reproductive organs, adipose tissue, pancreas, spleen, adrenal and the eye. This review describes the classical RAS as a framework upon which the newest discoveries in the RAS are described. These include the discovery of new enzymatic pathways by which novel angiotensinergic signaling molecules are formed, the expanding number of angiotensin receptor subtypes and molecules that transduce their increasing array of cellular responses. This new understanding is leading to the development of new drugs that can mimic or promote the axes of the RAS that counteract the classical axis that causes its pathophysiological actions.