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Characterization of cardiac angiotensin converting enzyme (ACE) and in vivo inhibition following oral quinapril to rats
Author(s) -
Fabris Bruno,
Yamada Hiroshi,
Cubela Rose,
Jackson Bruce,
Mendelsohn Frederick A.O.,
Johnston Colin I.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb15862.x
Subject(s) - quinapril , angiotensin converting enzyme , lisinopril , medicine , ace inhibitor , endocrinology , in vivo , potency , ramipril , enzyme inhibitor , lung , radioligand , chemistry , enzyme , pharmacology , biology , in vitro , biochemistry , blood pressure , receptor , microbiology and biotechnology
1 Angiotensin converting enzyme (ACE) from the rat heart and lung was studied by use of the radioligand [ 125 I]‐351A. 2 Displacement of the bound radioinhibitor [ 125 I]‐351A was used to assess the relative potency of six ACE inhibitors in rat heart and lung homogenates and estimate the binding association constant ( K A ). 3 The K A for atrial preparations was significantly higher than that of the lung ( P < 0.025) and also the ventricles ( P < 0.005). Ventricular preparations and preparations from the lung also differed significantly ( P < 0.05). These differences in K A 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 > perindoprilat > 351A > lisinopril > 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 K A noted have only a limited potential biological significance. The difference in K A may reflect variations in the structure or conformation of ACE in different tissues.