Local Renin-Angiotensin Systems in Cardiovascular Tissues: Localization and Functional Role

In its classical definition, the renin-angiotensin system (RAS) acts predominantly by endocrine mechanisms. This view has been modified since several components of the RAS and their mRNAs were found in peripheral tissues. These findings gave rise to the concept of local tissue renin-angiotensin systems. Although no cells of cardiovascular organs containing a complete RAS have been identified as of this writing, angiotensinogen and angiotensin-converting enzyme (ACE) are most likely synthesized within the vasculature for example. Local synthesis of renin may be limited to very small amounts, but uptake of renin from the circulation is very likely. The function of local RASs is shown by reduction of blood pressure by ACE inhibitors, which correlates better with the inhibition of ACE activity in certain tissues than with its activity in the plasma. Further studies have put forward the notion that the circulating RAS could mainly be important for acute hemodynamic stability, whereas the tissue RAS could be involved in more long term maintenance of hemodynamics. This review will try to summarize the findings leading to the concept of a local tissue renin-angiotensin system, and discuss interactions between the circulating and the local RAS in the light of recent experimental findings.