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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/H3019    most recent 01198.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Trask, A. J. Articles by Ferrario, C. M. Search for Related Content PubMed PubMed Citation Articles by Trask, A. J. Articles by Ferrario, C. M.

Primary role of angiotensin-converting enzyme-2 in cardiac production of angiotensin-(1–7) in transgenic Ren-2 hypertensive rats

¹The Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina; and ²Charité-University Medicine Berlin, Berlin, Germany

Submitted 1 November 2006 ; accepted in final form 12 February 2007

Angiotensin-converting enzyme-2 (ACE2) converts angiotensin II (ANG II) to angiotensin-(1–7) [ANG-(1–7)], and this enzyme may serve as a key regulatory juncture in various tissues. Although the heart expresses ACE2, the extent that the enzyme participates in the cardiac processing of ANG II and ANG-(1–7) is equivocal. Therefore, we utilized the Langendorff preparation to characterize the ACE2 pathway in isolated hearts from male normotensive Sprague-Dawley [Tg^(–)] and hypertensive [mRen2]27 [Tg⁽⁺⁾] rats. During a 60-min recirculation period with 10 nM ANG II, the presence of ANG-(1–7) was assessed in the cardiac effluent. ANG-(1–7) generation from ANG II was similar in both the normal and hypertensive hearts [Tg^(–): 510 ± 55 pM, n = 20 vs. Tg⁽⁺⁾: 497 ± 63 pM, n = 14] with peak levels occurring at 30 min after administration of the peptide. ACE2 inhibition (MLN-4760, 1 µM) significantly reduced ANG-(1–7) production by 83% (57 ± 19 pM, P < 0.01, n = 7) in the Tg⁽⁺⁾ rats, whereas the inhibitor had no significant effect in the Tg^(–) rats (285 ± 53 pM, P > 0.05, n = 10). ACE2 activity was found in the effluent of perfused Tg^(–) and Tg⁽⁺⁾ hearts, and it was highly associated with ACE2 protein expression (r = 0.78). This study is the first demonstration for a direct role of ACE2 in the metabolism of cardiac ANG II in the hypertrophic heart of hypertensive rats. We conclude that predominant expression of cardiac ACE2 activity in the Tg⁽⁺⁾ may be a compensatory response to the extensive cardiac remodeling in this strain.

angiotensin II; hypertension; isolated heart

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