Linked Life Data

10856268

Source:http://linkedlifedata.com/resource/pubmed/id/10856268

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-7-19
pubmed:abstractText
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 toward the 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 normotensive subjects. 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 endopeptidase inhibitors. A differential selectivity may explain some peculiar properties observed with some ACE inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0194-911X
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1226-31
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10856268-Adolescent, pubmed-meshheading:10856268-Adult, pubmed-meshheading:10856268-Angiotensin-Converting Enzyme Inhibitors, pubmed-meshheading:10856268-Animals, pubmed-meshheading:10856268-CHO Cells, pubmed-meshheading:10856268-Catalytic Domain, pubmed-meshheading:10856268-Cricetinae, pubmed-meshheading:10856268-Cross-Over Studies, pubmed-meshheading:10856268-Double-Blind Method, pubmed-meshheading:10856268-Fosinopril, pubmed-meshheading:10856268-Humans, pubmed-meshheading:10856268-Hydrolysis, pubmed-meshheading:10856268-Kinetics, pubmed-meshheading:10856268-Male, pubmed-meshheading:10856268-Molecular Sequence Data, pubmed-meshheading:10856268-Neprilysin, pubmed-meshheading:10856268-Oligopeptides, pubmed-meshheading:10856268-Peptidyl-Dipeptidase A, pubmed-meshheading:10856268-Pyridines, pubmed-meshheading:10856268-Sodium, pubmed-meshheading:10856268-Substrate Specificity, pubmed-meshheading:10856268-Thiazepines
pubmed:year
2000
pubmed:articleTitle
In vitro and in vivo inhibition of the 2 active sites of ACE by omapatrilat, a vasopeptidase inhibitor.
pubmed:affiliation
Centre d'Investigations Cliniques 9201, Assistance Publique des H¿opitaux de Paris/INSERM, H¿opital Broussais, Paris, France.
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't