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Entry
map04614                    Pathway                                

Name
Renin-angiotensin system
Description
The renin-angiotensin system (RAS) is a peptidergic system with endocrine characteristics regarding to the regulation of the blood pressure and hydro-electrolytic balance. In the classical RAS, the enzyme renin cleaves its substrate angiotensinogen (Agt) forming the decapeptide angiotensin I that is in turn cleaved by angiotensin-converting enzyme (ACE) to produce the angiotensin II (Ang II), a key player of this system. Ang II activates its AT1 receptor (AT1R), the principal receptor that mediates the majority of the known actions of Ang II in the kidney, including vasoconstriction, renal sodium (Na+) reabsorption, and aldosterone secretion, increasing blood pressure and contributing to the development of hypertension. In addition to (ACE)/Ang II/AT1R and AT2R axis, other signaling pathways in the RAS, such as ACE2/angiotensin-(1-7)/Mas and Ang IV/IRAP, and other active peptide of the RAS, with physiological relevance as Ang III, Ang A and alamandine, are now widely recognized.
Class
Organismal Systems; Endocrine system
BRITE hierarchy
Pathway map
map04614  Renin-angiotensin system
map04614

Ortholog table
Disease
H00541  Autosomal dominant tubulointerstitial kidney disease
H00575  Renal tubular dysgenesis
H01456  Diabetic nephropathy
H01457  Diabetic retinopathy
H02011  Familial juvenile hyperuricemic nephropathy
Other DBs
GO: 0002003
Reference
  Authors
Kramkowski K, Mogielnicki A, Buczko W.
  Title
The physiological significance of the alternative pathways of angiotensin II production.
  Journal
J Physiol Pharmacol 57:529-39 (2006)
Reference
  Authors
Danilczyk U, Eriksson U, Oudit GY, Penninger JM.
  Title
Physiological roles of angiotensin-converting enzyme 2.
  Journal
Cell Mol Life Sci 61:2714-9 (2004)
DOI:10.1007/s00018-004-4241-6
Reference
  Authors
Warner FJ, Smith AI, Hooper NM, Turner AJ.
  Title
Angiotensin-converting enzyme-2: a molecular and cellular perspective.
  Journal
Cell Mol Life Sci 61:2704-13 (2004)
DOI:10.1007/s00018-004-4240-7
Reference
  Authors
Kurdi M, De Mello WC, Booz GW.
  Title
Working outside the system: an update on the unconventional behavior of the renin-angiotensin system components.
  Journal
Int J Biochem Cell Biol 37:1357-67 (2005)
DOI:10.1016/j.biocel.2005.01.012
Reference
  Authors
Burrell LM, Johnston CI, Tikellis C, Cooper ME.
  Title
ACE2, a new regulator of the renin-angiotensin system.
  Journal
Trends Endocrinol Metab 15:166-9 (2004)
DOI:10.1016/j.tem.2004.03.001
Reference
  Authors
von Bohlen und Halbach O, Albrecht D.
  Title
The CNS renin-angiotensin system.
  Journal
Cell Tissue Res 326:599-616 (2006)
DOI:10.1007/s00441-006-0190-8
Reference
  Authors
Schmaier AH
  Title
The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction.
  Journal
Am J Physiol Regul Integr Comp Physiol 285:R1-13 (2003)
DOI:10.1152/ajpregu.00535.2002
Reference
  Authors
Eriksson U, Danilczyk U, Penninger JM.
  Title
Just the beginning: novel functions for angiotensin-converting enzymes.
  Journal
Curr Biol 12:R745-52 (2002)
DOI:10.1016/S0960-9822(02)01255-1
Reference
  Authors
Dielis AW, Smid M, Spronk HM, Hamulyak K, Kroon AA, ten Cate H, de Leeuw PW.
  Title
The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikrein-kinin systems.
  Journal
Hypertension 46:1236-42 (2005)
DOI:10.1161/01.HYP.0000193538.20705.23
Reference
  Authors
Kuba K, Imai Y, Penninger JM.
  Title
Angiotensin-converting enzyme 2 in lung diseases.
  Journal
Curr Opin Pharmacol 6:271-6 (2006)
DOI:10.1016/j.coph.2006.03.001
Reference
  Authors
Erdos EG, Jackman HL, Brovkovych V, Tan F, Deddish PA.
  Title
Products of angiotensin I hydrolysis by human cardiac enzymes potentiate bradykinin.
  Journal
J Mol Cell Cardiol 34:1569-76 (2002)
DOI:10.1006/jmcc.2002.2080
Reference
  Authors
Shrimpton CN, Smith AI, Lew RA.
  Title
Soluble metalloendopeptidases and neuroendocrine signaling.
  Journal
Endocr Rev 23:647-64 (2002)
DOI:10.1210/er.2001-0032
Reference
  Authors
Jackman HL, Massad MG, Sekosan M, Tan F, Brovkovych V, Marcic BM, Erdos EG.
  Title
Angiotensin 1-9 and 1-7 release in human heart: role of cathepsin A.
  Journal
Hypertension 39:976-81 (2002)
DOI:10.1161/01.HYP.0000017283.67962.02
Reference
  Authors
Lundequist A, Tchougounova E, Abrink M, Pejler G.
  Title
Cooperation between mast cell carboxypeptidase A and the chymase mouse mast cell protease 4 in the formation and degradation of angiotensin II.
  Journal
J Biol Chem 279:32339-44 (2004)
DOI:10.1074/jbc.M405576200
Reference
  Authors
Kehoe PG, Wilcock GK.
  Title
Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer's disease?
  Journal
Lancet Neurol 6:373-8 (2007)
DOI:10.1016/S1474-4422(07)70077-7
Reference
  Authors
Ferrao FM, Lara LS, Lowe J
  Title
Renin-angiotensin system in the kidney: What is new?
  Journal
World J Nephrol 3:64-76 (2014)
DOI:10.5527/wjn.v3.i3.64
Reference
  Authors
Zhuo JL, Ferrao FM, Zheng Y, Li XC
  Title
New frontiers in the intrarenal Renin-Angiotensin system: a critical review of classical and new paradigms.
  Journal
Front Endocrinol (Lausanne) 4:166 (2013)
DOI:10.3389/fendo.2013.00166
Reference
  Authors
Unger T, Paulis L, Sica DA
  Title
Therapeutic perspectives in hypertension: novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches.
  Journal
Eur Heart J 32:2739-47 (2011)
DOI:10.1093/eurheartj/ehr253
Reference
  Authors
Fyhrquist F, Saijonmaa O
  Title
Renin-angiotensin system revisited.
  Journal
J Intern Med 264:224-36 (2008)
DOI:10.1111/j.1365-2796.2008.01981.x
Reference
  Authors
Yugandhar VG, Clark MA
  Title
Angiotensin III: a physiological relevant peptide of the renin angiotensin system.
  Journal
Peptides 46:26-32 (2013)
DOI:10.1016/j.peptides.2013.04.014
Reference
  Authors
Etelvino GM, Peluso AA, Santos RA
  Title
New components of the renin-angiotensin system: alamandine and the MAS-related G protein-coupled receptor D.
  Journal
Curr Hypertens Rep 16:433 (2014)
DOI:10.1007/s11906-014-0433-0
KO pathway
ko04614   

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