CURRENT CONCEPT OF THE RENIN-ANGIOTENSIN SYSTEM

Traditionally, the renin angiotensin system (RAS) has been thought of primarily as an endocrine system that delivers circulating angiotensin II to target tissues. This peptide is a potent vasoconstrictor and a primary stimulus for aldosterone secretion. In addition, angiotensin I I has many other targets such as kidney, heart and brain, from which i t elicits different specific responses. Numerous studies using pharmac ologic or immunologic inhibitors of the system have shown an important role for the circulating RAS in blood pressure and electrolyte as wel l as fluid homeostasis. Although it acts as a classical circulating en docrine system, there is increasing evidence to show that the RAS may also have an important local autocrine or paracrine role in a variety of tissues since it has been shown that the RAS components are present in all of these tissues. In addition, several investigators recently demonstrated the expression of renin and angiotensinogen genes in mult iple tissues, which strongly suggests that these proteins are locally synthesized. Moreover, it has been demonstrated that tissue RAS is ind ependently regulated from circulating system under different pathologi cal situations such as hypertension. As a result, the concept of the R AS as an endocrine system alone is in question. Locally expressed RAS may be involved with the regulation of individual tissue function inde pendent of the circulating counterpart. However, the importance of the se local systems in circulatory control and body volume homeostasis ha s yet to be defined. It has been proposed that the main function of th e circulating RAS is to provide short-term cardiorenal homeostasis. Th e tonic control (e.g., adrenal and kidney) is influenced by the intrin sic tissue RAS. This new concept provides a broader outlook on the RAS and challenges its traditional endocrine role.