Increased angiotensin-(1-7)-forming activity in failing @entity1 heart ventricles: evidence for upregulation of the angiotensin-converting enzyme Homologue XXXX .

@entity1 @entity12064 @entity120 @entity2282 @entity1000 @entity15505
BACKGROUND: The formation of angiotensin-(1-7) from either angiotensin (Ang) I or Ang II in failing @entity1 hearts is not well understood. METHODS AND RESULTS: Angiotensinase activity in left and right ventricular membranes from 14 @entity1000 ( @entity1000 ), 8 @entity120 ( @entity120 ), and 13 nonfailing @entity1 hearts was measured with either 125I-Ang I or 125I-Ang II as substrate. Ang-(1-7)-forming activity from 125I-Ang I was inhibited by @entity12064 . With 125I-Ang II as substrate, Ang-(1-7) formation was inhibited by the @entity15505 -specific inhibitor C16. Western blotting with an anti- @entity15505 antibody confirmed the presence of @entity15505 . Angiotensinase activity with 125I-Ang I as substrate was increased in failing @entity1000 left ventricles (LVs) compared with nonfailing LVs (P<0.001). Ang-(1-7)-forming activity with 125I-Ang II as substrate was increased in both failing LVs and right ventricles (RVs) of @entity1000 hearts and only in failing RVs of @entity120 hearts ( @entity120 LV, 51.12+/-5.25; @entity120 RV, 89.97+/-11.21; @entity1000 LV, 139.7+/-21.96; and @entity1000 RV, 192.7+/-5.43; NF LV, 32.89+/-5.38; NF RV 40.49+/-10.66 fmol/min per milligram (P<0.05 @entity120 RV versus @entity120 LV; P<0.05 @entity120 RV versus NF RV; P<0.001 @entity1000 LV versus NF LV; P<0.001 @entity1000 RV versus NF RV). CONCLUSIONS: Ang-(1-7)-forming activity from both Ang I and Ang II was increased in failing @entity1 heart ventricles but was mediated by at least two different angiotensinases. The first, which demonstrated substrate preference for Ang I, was @entity2282 ( @entity2282 )-like. The second was @entity15505 , as demonstrated by Western blotting and inhibition of activity with C16.
