Angiotensin-(1-7) formation in the intact human heart: in vivo dependence on angiotensin II as substrate.
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.


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.
D000328:Adult; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*
D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)