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Renin‐Substrate Reaction: An Embarkation Premise

THE EXPANDING scheme of the renin-angiotensin system as shown in Figure 1, with many tentative and unproven links, is presented as the first embarkation premise. This symposium is limited to a consideration of the system leading to the generation of the end product "angiotensin." Angiotensin availability appears to be regulated predominantly by the generating machinery and to a lesser extent by its degradation,' even though overall angiotensin clearance shows adaptive increase in response to accelerated production.' The concept is further strengthened if availability of angiotensin to the receptor sites is considered in terms of local generation in the organ or the tissue, rather than through a maintained level of the circulating peptide. Accordingly, the initial rate of local generation in proximity to the receptor sites may be critical. Since all of the known effects of the entire system, proximate and remote, appear to be exerted through the end product generation, its control is of pivotal importance in the study of the biological importance of the renin-angiotensin system. In this regard, the possibility of a biological role for enzymes other than renin (Fig. 1) capable, under limited conditions, of generating angiotensin I, and particularly the "tonin system," capable perhaps of a direct and local genertion of angiotensin II in the tissues, also deserves a serious attention and further exploration.