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This Article Full Text Full Text (PDF) All Versions of this Article: 93/5/613    most recent expphysiol.2007.040246v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Garabelli, P. J. Articles by Chappell, M. C. PubMed PubMed Citation Articles by Garabelli, P. J. Articles by Chappell, M. C. Related Collections Genomic Physiology

¹ The Hypertension and Vascular Disease Center, Winston-Salem, NC, USA ² Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA ³ Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria

Angiotensin-converting enzyme 2 (ACE2), a homologue of angiotensin-converting enzyme (ACE), converts angiotensin (Ang) I to Ang(1–9) and Ang II to Ang(1–7), but does not directly process Ang I to Ang II. Cardiac function is compromised in ACE2 null mice; however, the importance of ACE2 in the processing of angiotensin peptides within the murine heart is not known. We determined the metabolism of angiotensins in wild-type (WT), ACE (ACE^–/–) and ACE2 null mice (ACE2^–/–). Angiotensin II was converted almost exclusively to Ang(1–7) in the cardiac membranes of WT and ACE^–/– strains, although generation of Ang(1–7) was greater in the ACE^–/– mice (27.4 ± 4.1 versus 17.5 ± 3.2 nmol^–1 mg h^–1 for WT). The ACE2 inhibitor MLN4760 significantly attenuated Ang II metabolism and the subsequent formation of Ang(1–7) in both strains. In the ACE2^–/– hearts, Ang II metabolism and the generation of Ang(1–7) were significantly attenuated; however, the ACE2 inhibitor reduced the residual Ang(1–7)-forming activity in this strain. Angiotensin I was primarily converted to Ang(1–9) (WT, 28.9 ± 3.1 nmol^–1 mg h^–1; ACE^–/–, 49.8 ± 5.3 nmol^–1 mg h^–1; and ACE2^–/–, 35.9 ± 5.4 nmol^–1 mg h^–1) and to smaller quantities of Ang(1–7) and Ang II. Although the ACE2 inhibitor had no effect on Ang(1–9) formation, the carboxypeptidase A inhibitor benzylsuccinate essentially abolished the formation of Ang(1–9) and increased the levels of Ang I in cardiac membranes. In conclusion, our studies in the murine heart suggest that ACE2 is the primary pathway for the metabolism of Ang II and the subsequent formation of Ang(1–7), a peptide that, in contrast to Ang II, exhibits both antifibrotic and antiproliferative actions.

(Received 20 November 2007; accepted after revision 13 March 2008; first published online 20 March 2008)
Corresponding author M. C. Chappell: Hypertension & Vascular Disease Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1032. Email: mchappel{at}wfubmc.edu

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				M. K. Raizada and J. F. R. Paton Recent advances in the renin-angiotensin system: angiotensin-converting enzyme 2 and (pro)renin receptor Exp Physiol, May 1, 2008; 93(5): 517 - 518. [Full Text] [PDF]