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

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Item Type:	Article
Title:	Primary role of angiotensin converting enzyme 2 in cardiac production of angiotensin-(1-7) in transgenic Ren-2 hypertensive rats
Creators Name:	Trask, A.J., Averill, D.B., Ganten, D., Chappell, M.C. and Ferrario, C.M.
Abstract:	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-minute 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 versus Tg((+)): 497 +/- 63 pM, n=14) with peak levels occurring at 30 minutes after administration of the peptide. ACE2 inhibition (MLN-4760, 1microM) 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. Key words: angiotensin II, hypertension, isolated heart.
Keywords:	Angiotensin II, Hypertension, Isolated Heart
Source:	American Journal of Physiology Heart and Circulatory Physiology
ISSN:	0363-6135
Publisher:	American Physiological Society
Volume:	292
Number:	6
Page Range:	H3019-H3024
Date:	1 June 2007
Official Publication:	https://doi.org/10.1152/ajpheart.01198.2006
PubMed:	View item in PubMed

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