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(Circulation. 2003;108:1679.)
© 2003 American Heart Association, Inc.

Brief Rapid Communications

Angiotensin-(1-7) Formation in the Intact Human Heart

In Vivo Dependence on Angiotensin II as Substrate

From The Heart Institute, Albany Medical Center, Albany, NY (L.S.Z., C.C.C.), and The University of Colorado Health Sciences Center, Denver (G.E.M., M.R.B.).

Correspondence to Lawrence S. Zisman, MD, FACC, The Heart Institute, MC 55, Albany Medical College, 47 New Scotland Ave, Albany, NY 12208. E-mail zismanl{at}mail.amc.edu

Received January 7, 2003; de novo received May 13, 2003; revision received August 8, 2003; accepted August 11, 2003.

Background— Several enzymes that hydrolyze angiotensin I (Ang I) and Ang II to Ang-(1-7) have been identified, but their relative importance in the intact human heart is not known.

Methods and Results— Intracoronary (IC) ¹²³I-Ang I was administered to 4 heart transplantation recipients. Arterial and coronary sinus (CS) samples were taken before and after coadministration of IC enalaprilat. ¹²³I-Ang metabolites were separated by high-pressure liquid chromatography, and ¹²³I-Ang-(1-7) and ¹²³I-Ang II were quantified across the myocardial circulation. ¹²³I-Ang II formation (as measured by fractional conversion) at steady state was 0.43±0.05 and was reduced to 0.042±0.02 after IC enalaprilat (P<0.01). The fractional conversion of ¹²³I-Ang-(1-7) was 0.198±0.032 but was reduced to 0.06±0.01 during IC enalaprilat (P<0.01). Net Ang II production at steady state was 2720±704 pg/min. Ang-(1-7) production was 3489±768 pg/min. After IC enalaprilat, Ang II production fell to 436±66.8 pg/min (P<0.05 versus Ang II production). After suppression of Ang II production with enalaprilat, there was net uptake of Ang-(1-7): -289±144 pg/min (P<0.05).

Conclusions— Ang-(1-7) was formed in the intact human myocardial circulation and was decreased when Ang II formation was suppressed. These data indicate that the major pathway for Ang-(1-7) generation in the intact human heart was dependent on substrate availability of Ang II. Ang-(1-7)–forming enzymes that demonstrate substrate preference for Ang II are likely to play an important role in the regulation of Ang-(1-7) formation in the intact human heart.

Key Words: angiotensin • enzymes • cardiomyopathy

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