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 (F 0 and F 2 ) 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 F 0 and F 2 were higher in BB rats than in LL rats (PϽ0.01), 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 (PϽ0.05 Key Words: angiotensin-converting enzyme Ⅲ angiotensin Ⅲ polymorphism Ⅲ neutral endopeptidase A ngiotensin I-converting enzyme plays an important role in the regulation of the renin angiotensin system (RAS) by hydrolyzing angiotensin (Ang) I to Ang II and degrading bradykinin to bradykinin-(1-7) and Ang-(1-7) to Ang-(1-5), both inactive peptides. In this way, ACE activity influences circulating and tissue levels of Ang II, contributes to regulate the vasculature tone, and may have some effects on cardiac and vascular mass and structure. 1 Neutral endopeptidase (NEP, enkephalinase, neprilysin, EC 3.4.24.11) is a transmembrane zinc metalloendopeptidase, present at the surface of several tissues. 2 NEP also participates in the RAS, cleaving Ang I and Ang II. 3,4 The action of NEP on Ang I generates Ang-(1-7), an heptapeptide with vasodilator activity. The physiological effects of Ang-(1-7) are opposite those of Ang II and would favor a blood pressure-lowering effect under conditions of high Ang II activity. 3,4 In humans, the ACE gene insertion/deletion (I/D) polymorphism is due to the presence (insertion) or absence (deletion) of a 287-bp sequence in the intron 16 on the chromosome 17q23 5 and determines plasma ACE levels by 50%. The D allele is associated with increased ACE and possibly increased Ang II levels. 6,7 Recent evidence suggests that the DD genotype-with higher plasma ACE activity-is associated with higher risk of hypertension in men. 8 A similar polymorphism has been observed in normotensive rats, whereas homozygous rats for the Lou and Lewis microsatellite alleles have lower ACE activity than that of homozygous rats for the Brown Norway microsatellite allele (BB). 9 It remains unknown whether NEP activity-because of its interaction with Ang I and Ang II as well as with bradykinin-is modulated by ACE expression. Because higher ACE activity will decrease Ang I and bradykinin levels and increase Ang II levels, we hypothesized that an inverse relationship between ACE expression (genetically determined) and NEP activity might exist. To test this hypothesis, NEP activity was determined in serum and in different tissues from male Lewis homozygous (LL, genetically with low ACE activity) and BB rats (genetically with high ACE activity) in F 0 and in homozygous F 2. These rats were also characterized by their ACE genotype and circ...
Neutral endopeptidase (NEP) hydrolyses angiotensins (Ang) I and II and generates angiotensin-(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 (Po0.001). A significant effect of the ACE polymorphism and of the hypertensive status on ACE activity was observed (Po0.001). In normotensive DD ACE subjects, NEP activity was 0.30 7 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 (Po0.001). In the hypertensive DD ACE patients, NEP activity was 0.47 7 0.03 U/mg. An effect of the I/D ACE genotypes on NEP activity (Po0.04) and an interaction effect between the I/D ACE genotype and the hypertensive status were also observed (Po0.001). 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.
M e d i c a 252 1,3% rispettivamente per le fasce di età 15-25, 26-35 e >35 anni, mentre quelli positivi per C. trachomatis 5,5%, 11,3% e 6,7% rispettivamente per le 3 fasce di età considerate. Per la popolazione femminile sono risultate positive per N. gonorrhoeae solo donne di età compresa tra i 15 e i 25 anni (0,6%), mentre sono risultate positive tutte le fasce di età considerate per C. trachomatis (2,9%, 2,0% e 1,6% rispettivamente). Conclusioni. La casistica raccolta non fa parte esclusivamente di centri MTS ed è auspicabile che sia possibile in un momento successivo estendere l'indagine epidemiologica ad un bacino più ampio.
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