Angiotensin I-converting enzyme modulates neutral endopeptidase activity in the rat

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 activity. Accordingly, circulating and tissue NEP and ACE activities were measured by fluorometry in homozygous rats (F0 and F2) for the Lewis microsatellite allele (LL, low ACE) and for the Brown Norway microsatellite allele (BB, high ACE). Plasma, lung, and aortic ACE activities in F0 and F2 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 F0 and F2 homozygous (P,0.05). Plasma ACE activity was inversely correlated with serum (r520.6 and 20.598 in F0 and F2, respectively; P,0.03) and lung NEP activities (r520.77 in F0 and r520.59 in F2, P,0.01). Aortic ACE and NEP activities were also correlated (r520.696 and 20.584 in F0 and F2, respectively; P,0.03). In conclusion, genetically determined high ACE expression in rats is inversely related to tissue NEP activity, which could determine lower angiotensin-(1-7) tissue levels. (Hypertension. 2001;38[part 2]:650-654.)