Renin-angiotensin system revisited.
New components and functions of the renin-angiotensin system (RAS) are still being unravelled. The classical RAS as it looked in the middle 1970s consisted of circulating renin, acting on angiotensinogen to produce angiotensin I, which in turn was converted into angiotensin II (Ang II) by angiotensin-converting enzyme (ACE). Ang II, still considered the main effector of RAS was believed to act only as a circulating hormone via angiotensin receptors, AT1 and AT2. Since then, an expanded view of RAS has gradually emerged. Local tissue RAS systems have been identified in most organs. Recently, evidence for an intracellular RAS has been reported. The new expanded view of RAS therefore covers both endocrine, paracrine and intracrine functions. Other peptides of RAS have been shown to have biological actions; angiotensin 2-8 heptapeptide (Ang III) has actions similar to those of Ang II. Further, the angiotensin 3-8 hexapeptide (Ang IV) exerts its actions via insulin-regulated amino peptidase receptors. Finally, angiotensin 1-7 (Ang 1-7) acts via mas receptors. The discovery of another ACE2 was an important complement to this picture. The recent discovery of renin receptors has made our view of RAS unexpectedly complex and multilayered. The importance of RAS in cardiovascular disease has been demonstrated by the clinical benefits of ACE inhibitors and AT1 receptor blockers. Great expectations are now generated by the introduction of renin inhibitors. Indeed, RAS regulates much more and diverse physiological functions than previously believed.
Fyhrquist
F
F
Minerva Institute for Medical Research and Department of Internal Medicine, Helsinki University Central Hospital, Helsinki, Finland. frej.fyhrquist@helsinki.fi
Saijonmaa
O
O
D000803:Angiotensin I / Q000502:physiology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000502:physiology; D000805:Angiotensin III / Q000502:physiology; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D010446:Peptide Fragments / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000502:physiology; D000093342:Prorenin Receptor
D000803:Angiotensin I; D000804:Angiotensin II; D000805:Angiotensin III; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D007703:Peptidyl-Dipeptidase A; D044140:Receptor, Angiotensin, Type 1; D011956:Receptors, Cell Surface; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; C000705307:ACE2 protein, human; C118790:angiotensin I (1-7)
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