Local RAS

The concept of a circulating RAS is well established and known to play an endocrine role in the regulation of fluid homeostasis (see Section 4.1, Chapter 4). However, it is more appropriate to view the RAS in the contemporary notion as an “angiotensin-generating system”, which consists of angiotensinogen, angiotensin-generating enzymes, and angiotensins, as well as their receptors. Some RASs can be termed as “complete”, having renin and ACE involved in the biosynthesis of angiotensin II peptide, i.e. in a renin and/or ACE-dependent manner which is exemplified in the circulating RAS. On the other hand, some RAS can be termed as “partial”, having alternate enzymes to renin and ACE, such as chymase and ACE2 (see Section 4.3, Chapter 4) available for the generation of angiotensin II and other bioactive angiotensin peptides in the biosynthetic cascade, i.e. in a renin and/or ACE-independent manner. Complete vs. partial RASs can be exemplified in the so-called intrinsic angiotensin-generating system or local RAS; for example, a local and functional RAS with renin and ACE-dependent but a renin-independent pathway have been indentified in the pancreas and carotid body, respectively. In the past two decades, local RASs have gained increasing recognition especially with regards to their clinical importance. Distinct from the circulating RAS, these functional local RASs exist in such diverse tissues and organs as the pancreas, liver, intestine, heart, kidney, vasculature, carotid body, and adipose, as well as the nervous, reproductive, and digestive systems. Taken into previous findings from our laboratory and others together, Table 5.1 is a summary of some recently identified local RASs in various levels of tissues and organs.