Angiotensin I is a substrate for both ACE and for neutral endopeptidase 24.
11 (NEP). We hypothesized that high ACE expression is related to low NEP ac
tivity. Accordingly, circulating and tissue NEP and ACE activities were mea
sured by fluorometry in homozygous rats (FO and 172) for the Lewis microsat
ellite allele (LL, low ACE) and for the Brown Norway microsatellite allele
(BB, high ACE). Plasma, lung, and aortic ACE activities in F-0 and F-2 were
higher in BB rats than in LL rats (P <0.01), whereas left ventricular ACE
activity was similar in both genotypes. In contrast, NEP activity in the LL
group was higher in the serum, aorta, and lungs in F-0 and F-2 homozygous
(P <0.05). Plasma ACE activity was inversely correlated with serum (r=-0.6
and -0.598 in F-0 and F-2, respectively; P <0.03) and lung NEP activities (
r=-0.77 in F-0 and r=-0.59 in F-2, P <0.01). Aortic ACE and NEP activities
were also correlated (r=-0.696 and -0.584 in F-0 and F-2, respectively; P <
0.03). In conclusion, genetically determined high ACE expression in rats is
inversely related to tissue NEP activity, which could determine lower angi
otensin-(1-7) tissue levels.