{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T06:22:29Z","timestamp":1782886949875,"version":"3.54.5"},"reference-count":32,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:p>Angiotensin-converting enzyme-2 (ACE2) converts angiotensin II (ANG II) to angiotensin-(1\u20137) [ANG-(1\u20137)], 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\u20137) is equivocal. Therefore, we utilized the Langendorff preparation to characterize the ACE2 pathway in isolated hearts from male normotensive Sprague-Dawley [Tg<jats:sup>(\u2212)<\/jats:sup>] and hypertensive [mRen2]27 [Tg<jats:sup>(+)<\/jats:sup>] rats. During a 60-min recirculation period with 10 nM ANG II, the presence of ANG-(1\u20137) was assessed in the cardiac effluent. ANG-(1\u20137) generation from ANG II was similar in both the normal and hypertensive hearts [Tg<jats:sup>(\u2212)<\/jats:sup>: 510 \u00b1 55 pM, n = 20 vs. Tg<jats:sup>(+)<\/jats:sup>: 497 \u00b1 63 pM, n = 14] with peak levels occurring at 30 min after administration of the peptide. ACE2 inhibition (MLN-4760, 1 \u03bcM) significantly reduced ANG-(1\u20137) production by 83% (57 \u00b1 19 pM, P &lt; 0.01, n = 7) in the Tg<jats:sup>(+)<\/jats:sup>rats, whereas the inhibitor had no significant effect in the Tg<jats:sup>(\u2212)<\/jats:sup>rats (285 \u00b1 53 pM, P &gt; 0.05, n = 10). ACE2 activity was found in the effluent of perfused Tg<jats:sup>(\u2212)<\/jats:sup>and Tg<jats:sup>(+)<\/jats:sup>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<jats:sup>(+)<\/jats:sup>may be a compensatory response to the extensive cardiac remodeling in this strain.<\/jats:p>","DOI":"10.1152\/ajpheart.01198.2006","type":"journal-article","created":{"date-parts":[[2007,2,17]],"date-time":"2007-02-17T01:59:16Z","timestamp":1171677556000},"page":"H3019-H3024","source":"Crossref","is-referenced-by-count":49,"title":["Primary role of angiotensin-converting enzyme-2 in cardiac production of angiotensin-(1\u20137) in transgenic Ren-2 hypertensive rats"],"prefix":"10.1152","volume":"292","author":[{"given":"Aaron J.","family":"Trask","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Averill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlev","family":"Ganten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Chappell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos M.","family":"Ferrario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/58.9.B792"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1995.269.1.H313"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi114"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Chappell MC, Brosnihan KB, Diz DI, Ferrario CM.Identification of angiotensin-(1\u20137) in rat brain. 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