Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
In vitro and in vivo inhibition of the 2 active sites of ACE by omapatrilat, a vasopeptidase inhibitor
Autore:
Azizi, M; Massien, C; Michaud, A; Corvol, P;
Indirizzi:
Coll France, INSERM, U36, F-75005 Paris, France Coll France Paris FranceF-75005 nce, INSERM, U36, F-75005 Paris, France Hop Broussais, INSERM, Assistance Publ Hop Paris, Ctr Invest Clin 9201, F-75674 Paris, France Hop Broussais Paris France F-75674 vest Clin 9201, F-75674 Paris, France
Titolo Testata:
HYPERTENSION
fascicolo: 6, volume: 35, anno: 2000,
pagine: 1226 - 1231
SICI:
0194-911X(200006)35:6<1226:IVAIVI>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANGIOTENSIN-CONVERTING ENZYME; ASPARTYL-LYSYL-PROLINE; NEUTRAL ENDOPEPTIDASE; HOMOLOGOUS DOMAINS; HYDROLYSIS; SUBSTRATE; SELECTIVITY; PEPTIDE; HUMANS; PRO;
Keywords:
angiotensin-converting enzyme; angiotensin-converting enzyme inhibitors AcSDKP; human;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Corvol, P Coll France, INSERM, U36, 3 Rue Ulm, F-75005 Paris, France Coll France 3 Rue Ulm Paris France F-75005 -75005 Paris, France
Citazione:
M. Azizi et al., "In vitro and in vivo inhibition of the 2 active sites of ACE by omapatrilat, a vasopeptidase inhibitor", HYPERTENSIO, 35(6), 2000, pp. 1226-1231

Abstract

The vasopeptidase inhibitor omapatrilat inhibits both neutral endopeptidase and angiotensin-converting enzyme (ACE). The in vitro and in vivo inhibitory potency of omapatrilat and the specific ACE inhibitor fosinopril towardthe 2 active sites of ACE (called N- and C-domains) was investigated with the use of 3 substrates: angiotensin I, which is equally cleaved by the 2 ACE domains; hippuryl-histidyl-leucine, specific synthetic substrate of the C-domain in high salt conditions; and a newly synthesized specific substrate of the N-domain designed by acetylating the lysine residue of AcSDKP. In vitro, omapatrilat was 5 times more potent than fosinoprilat in inhibiting angiotensin I hydrolysis. Omapatrilat inhibited similarly both N- and C-domain hydrolysis, whereas fosinoprilat was slightly more specific for the N-domain, The in vivo selective inhibitory potency of single oral doses of 10 mg omapatrilat and 20 mg fosinopril were investigated in a double-blind, placebo-controlled, cross-over study in 9 mildly sodium-depleted normotensivesubjects. In accordance with the in vitro results, fosinopril appeared to be more specific for the N-domain than the C-domain in vivo, since plasma and urine AcSDKP concentrations were significantly higher than those observed with omapatrilat. This study shows that it is possible to assess separately in vitro and in vivo the selectivity of ACE or ACE/neutral endopeptidaseinhibitors. A differential selectivity may explain some peculiar properties observed with some ACE inhibitors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 13:57:31