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Review
. 2009 Jul;32(7):533-6.
doi: 10.1038/hr.2009.74. Epub 2009 May 22.

Devil and angel in the renin-angiotensin system: ACE-angiotensin II-AT1 receptor axis vs. ACE2-angiotensin-(1-7)-Mas receptor axis

Masaru Iwai  1 , Masatsugu Horiuchi
Affiliations
Review

Devil and angel in the renin-angiotensin system: ACE-angiotensin II-AT1 receptor axis vs. ACE2-angiotensin-(1-7)-Mas receptor axis

Masaru Iwai et al. Hypertens Res. 2009 Jul.

Abstract

Recent studies have established a new regulatory axis in the renin-angiotensin system (RAS). In this axis, angiotensin (Ang)-(1-7) is finally produced from Ang I or Ang II by the catalytic activity of angiotensin-converting enzyme 2 (ACE2). Ang-(1-7) shows actions different from those of AT(1) receptor stimulation, such as vasodilatation, natriuresis, anti-proliferation and an increase in the bradykinin-NO (nitric oxide) system. As the catalytic efficiency of ACE2 is approximately 400-fold higher with Ang II as a substrate than with Ang I, this axis is possibly acting as a counter-regulatory system against the ACE/Ang II/AT(1) receptor axis. The signaling pathway of the ACE2-Ang-(1-7) axis has not yet been totally and clearly understood. However, a recent report suggests that the Mas oncogene acts as a receptor for Ang-(1-7). Intracellular signaling through Mas is not clear yet. Several factors such as Akt phosphorylation, protein kinase C activation and mitogen-activated protein (MAP) kinase inhibition seem to be involved in this signaling pathway. Further investigations are needed to clarify the regulation and mechanism of action of ACE2 and Ang-(1-7). However, this second axis through ACE2 and Ang-(1-7) in RAS can be an important target for the therapy of cardiovascular and metabolic disorders.

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Figures

Figure 1
Figure 1
The role of AT1 receptor stimulation in hypertension and organ damage. NO, nitric oxide; CKD, chronic kidney disease.
Figure 2
Figure 2
The production of angiotensin-(1–7) by the angiotensin-converting enzyme 2 (ACE2).
Figure 3
Figure 3
Action of AT1 and AT2 receptors and Mas-mediated signaling. AT1, angiotensin-II type-1 receptor; AT2, angiotensin-II type-2 receptor; NO, nitric oxide.
Figure 4
Figure 4
The balance between ACE and ACE2 activities affects cardiovascular disorders. ACE, angiotensin-converting enzyme; Ang, angiotensin; AT1, angiotensin-II type-1 receptor; AT2, angiotensin-II type-2 receptor.
See this image and copyright information in PMC

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References

    1. de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000;52:415–472. - PubMed
    1. Daviet L, Lehtonen JY, Tamura K, Griese DP, Horiuchi M, Dzau VJ. Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor. J Biol Chem. 1999;274:17058–17062. doi: 10.1074/jbc.274.24.17058. - DOI - PubMed
    1. Nouet S, Amzallag N, Li JM, Louis S, Seitz I, Cui TX, Alleaume AM, Di Benedetto M, Boden C, Masson M, Strosberg AD, Horiuchi M, Couraud PO, Nahmias C. Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP. J Biol Chem. 2004;279:28989–28997. doi: 10.1074/jbc.M403880200. - DOI - PubMed
    1. Dzau V. The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. J Hypertens Suppl. 2005;23:S9–S17. doi: 10.1097/01.hjh.0000165623.72310.dd. - DOI - PubMed
    1. Kaschina E, Grzesiak A, Li J, Foryst-Ludwig A, Timm M, Rompe F, Sommerfeld M, Kemnitz UR, Curato C, Namsolleck P, Tschöpe C, Hallberg A, Alterman M, Hucko T, Paetsch I, Dietrich T, Schnackenburg B, Graf K, Dahlöf B, Kintscher U, Unger T, Steckelings UM. Angiotensin II type 2 receptor stimulation: a novel option of therapeutic interference with the renin-angiotensin system in myocardial infarction? Circulation. 2008;118:2523–2532. doi: 10.1161/CIRCULATIONAHA.108.784868. - DOI - PubMed

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