title: Characterization of cardiac angiotensin converting enzyme (ACE) and in vivo inhibition following oral quinapril to rats.
abstract: 1. Angiotensin converting enzyme (ACE) from the rat heart and lung was studied by use of the radioligand [125I]-351A. 2. Displacement of the bound radioinhibitor [125I]-351A was used to assess the relative potency of six ACE inhibitors in rat heart and lung homogenates and estimate the binding association constant (KA). 3. The KA for atrial preparations was significantly higher than that of the lung (P less than 0.025) and also the ventricles (P less than 0.005). Ventricular preparations and preparations from the lung also differed significantly (P less than 0.05). These differences in KA were noted for all six ACE inhibitors used to displace the radioligand. 4. The rank order of potency of the ACE inhibitors was quinaprilat = benazeprilat greater than perindoprilat greater than 351A greater than lisinopril greater than fosinoprilat. 5. Cardiac ACE inhibition was studied ex vivo following oral administration of quinapril to rats. Following 0.3 mg kg-1 quinapril, the time course and degree of inhibition of ventricular and atrial ACE were similar. 6. These results suggest that the detected differences in KA noted have only a limited potential biological significance. The difference in KA may reflect variations in the structure or conformation of ACE in different tissues.
authors.affiliation: University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Fabris
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: R
authors.initials: R
authors.lastname: Cubela
authors.forename: B
authors.initials: B
authors.lastname: Jackson
authors.forename: F A
authors.initials: FA
authors.lastname: Mendelsohn
authors.forename: C I
authors.initials: CI
authors.lastname: Johnston
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism*; D000818:Animals; D004151:Dipeptides; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007546:Isoquinolines / Q000097:blood; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000032:analysis*; D000077583:Quinapril; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D044005:Tetrahydroisoquinolines
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D007457:Iodine Radioisotopes; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C042037:L-proline, N2-((1S)-1-carboxy-3-phenylpropyl)-N6-((4-hydroxyphenyl)iminomethyl)-L-lysyl-; D007703:Peptidyl-Dipeptidase A; D000077583:Quinapril