[The 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 II has many other targets such as kidney, heart and brain, from which it elicits different specific responses. Numerous studies using pharmacologic or immunologic inhibitors of the system have shown an important role for the circulating RAS in blood pressure and electrolyte as well as fluid homeostasis. Although it acts as a classical circulating endocrine 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 have recently demonstrated the expression of renin and angiotensinogen genes in multiple tissues, which strongly suggests that these proteins are locally synthesized. Moreover, it has been demonstrated that tissue RAS is independently regulated from circulating system under different pathological situations such as hypertension. As a result, the concept of the RAS as an endocrine system alone is in question. Locally expressed RAS may be involved with the regulation of individual tissue function independent of the circulating counterpart. However, the importance of these local systems in circulatory control and body volume homeostasis has yet to be defined. It has been proposed that the main function of the circulating RAS is to provide short-term cardiorenal homeostasis. The tonic control (e.g., adrenal and kidney) is influenced by the intrinsic tissue RAS. This new concept provides a broader outlook on the RAS and challenges its traditional endocrine role.