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. Author manuscript; available in PMC: 2014 Mar 25.
Published in final edited form as: Clin Sci (Lond). 2012 Sep;123(5):273–284. doi: 10.1042/CS20120089

Figure 2. The circulating, tissue, and intracellular RASs.

Figure 2

Based on the site of Ang II generation (denoted as red dots), the RAS can be classified as the circulating, tissue, or the intracellular RAS. In the circulating RAS, Ang II is formed in the blood from AGT secreted by liver, by the actions of renin secreted from kidneys and ACE present on vascular endothelial cells. The circulating RAS represents an endocrine system. In the tissue RAS, Ang II synthesis occurs in the interstitial space from components largely produced in the same tissue. The tissue Ang II acts locally in an autocrine/paracrine manner. The intracellular RAS is defined by Ang II synthesis inside the cell, either in secretory vesicles (the secretory RAS) or in other cellular regions or organelles (the non-secretory RAS). Intracellular Ang II has been localized in the cytoplasm, mitochondria, and nuclei. Mitochondria and nuclei have also been demonstrated to contain angiotensin receptors. Ang II actions arising from an intracellular location are termed intracrine actions.