Circulating and tissue angiotensin systems

Abstract

Accumulating evidence indicates that the major site of angiotensin production in not in blood but in tissues, and results from the action of plasma-derived renin on plasma-derived angiotensinogen, together with the interaction of locally synthesized components. Both the production of angiotensin in tissues and the regulation of its production may be, to a greater or lesser extent, independent of the circulating RAS. This new concept of the RAS indicates a need to revise previous concepts concerning the role of angiotensin in hypertension. The development of these concepts has been greatly accelerated by the availability of more specific inhibitors of AII production and their therapeutic effectiveness in hypertension. Our increasing knowledge of the RAS has revealed it to be much more complex than previously thought. One immediate challenge is to obtain a clearer insight into the mechanisms and regulation of angiotensin production in vivo, in individual tissues, and within the multiple compartments of each tissue, including the brain. The application of hybridization in situ to monitor cellular levels of mRNA for renin and angiotensinogen will assist in this endeavor. However, there is also a need for the development of methodology able to measure the concentration of AII at the local receptor level, if the functional and pathogenic significance of local tissue angiotensin systems is to be established.