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(Hypertension. 2001;38:650.)
© 2001 American Heart Association, Inc.

Renin-Angiotensin System

Angiotensin I-Converting Enzyme Modulates Neutral Endopeptidase Activity in the Rat

Carla Oliveri; María Paz Ocaranza; Ximena Campos; Sergio Lavandero; Jorge E. Jalil

Department of Cardiovascular Diseases, Medical School, P. Catholic University of Chile (M.P.O., J.E.J.); and the Departments of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile (C.O., M.P.O., X.C., S.L.), Santiago, Chile.

Correspondence to Jorge E. Jalil, MD, Department of Cardiovascular Diseases, Medical School, P. Catholic University of Chile, Marcoleta 367, Santiago, Chile, E-mail jjalil{at}med.puc.cl; or Sergio Lavandero PhD, Department of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Olivos 1007, Santiago, Chile, E-mail slavander@uchile.cl

Abstract

Abstract—— 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 (r=-0.6 and -0.598 in F₀ and F₂, respectively; P<0.03) and lung NEP activities (r=-0.77 in F₀ and r=-0.59 in F₂, P<0.01). Aortic ACE and NEP activities were also correlated (r=-0.696 and -0.584 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.

Key Words: angiotensin-converting enzyme • angiotensin • polymorphism • neutral endopeptidase

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