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Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene polymorphism in humans

Journal of Human Hypertension volume 18, pages 119–125 (2004)Cite this article

Abstract

Neutral endopeptidase (NEP) hydrolyses angiotensins (Ang) I and II and generates angiotensin-(1-7) [Ang-(1-7)]. In humans, the insertion/deletion (I/D) angiotensin-I converting enzyme (ACE) gene polymorphism determined plasma ACE levels by 40%. In rats, a similar polymorphism determines ACE levels which are inversely associated to NEP activity. The objective of this study is to evaluate the relationship between ACE expression and plasma NEP activity in normotensive subjects and in hypertensive patients. In total, 58 consecutive patients with hypertension, evaluated in our Hypertension Clinic, were compared according to their ACE I/D genotypes with 54 control subjects in terms of both plasma ACE activity and NEP activities. Plasma ACE activity was elevated 51 and 70% in both DD ACE groups (normotensives and hypertensives) compared with their respective ID and II ACE groups (P<0.001). A significant effect of the ACE polymorphism and of the hypertensive status on ACE activity was observed (P<0.001). In normotensive DD ACE subjects, NEP activity was 0.30±0.02 U/ml, whereas in the normotensive II ACE and in the normotensive ID ACE subjects NEP activity was increased 65 and 48%, respectively (P<0.001). In the hypertensive DD ACE patients, NEP activity was 0.47±0.03 U/mg. An effect of the I/D ACE genotypes on NEP activity (P<0.04) and an interaction effect between the I/D ACE genotype and the hypertensive status were also observed (P<0.001). These results are consistent with a normal and inverse relationship between the ACE polymorphism and NEP activity in normotensive humans (as is also observed in rats). This normal relationship is not observed in hypertensive patients.

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Authors and Affiliations

  1. Department of Cardiovascular Diseases, Medical School, P. Catholic University of Chile, Marcoleta, Chile

    J E Jalil, M P Ocaranza, C Oliveri, S Córdova, I Godoy, G Chamorro & S Braun

  2. Department of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile

    C Oliveri & S Lavandero

  3. Department of Endocrinology, Medical School, P. Catholic University of Chile, Marcoleta, Chile

    C Fardella

  4. INSERM, Unité 460 (Remodelage Cardiovasculaire), Paris, France

    J-B Michel

  5. Fondap Center for Cellular Molecular Studies,

    S Lavandero

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  1. J E Jalil
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  2. M P Ocaranza
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Correspondence to J E Jalil.

Additional information

Grant support. Fondecyt 1000576, Ecos-Conicyt C99S01 Interchange Program and Fondap 15010006.

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Jalil, J., Ocaranza, M., Oliveri, C. et al. Neutral endopeptidase and angiotensin I converting enzyme insertion/deletion gene polymorphism in humans. J Hum Hypertens 18, 119–125 (2004). https://doi.org/10.1038/sj.jhh.1001646

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