title: Bradykinin metabolism in rat hearts with left-ventricular hypertrophy following myocardial infarction.
abstract: The aim of the present study was to assess the contribution of angiotensin I converting enzyme (ACE)and neutral endopeptidase (NEP) in the coronary degradation of bradykinin (BK) after left-ventricular hypertrophy following myocardial infarction (MI) in rats. Myocardial infarction was induced by left descendant coronary artery ligation, and the contribution of ACE and NEP in the degradation of exogenous BK after a single passage through the coronary bed was assessed at 2, 5, and 36 days post-MI. BK degradation rate (V(max)/Km) was found to be significantly lower in hearts at 36 days (3.30 +/- 0.28 min(-1)) compared with 2 days (4.39 +/- 0.32 min(-1)) for noninfarcted hearts, but this reduction was just above the statistical level of significance for post-MI hearts. In infarcted hearts, V(max)/Km was increased significantly 5 days post-MI (4.91 +/- 0.28 min(-1)) compared with the 2 and 36 day-groups (3.43 +/- 0.20 and 2.78 +/- 0.16 min(-1), respectively). The difference between noninfarcted and MI was significant only 2 days post-MI. Treatment with the vasopeptidase inhibitor, omapatrilat, showed that the relative contribution of ACE and NEP combined increased over time in infarcted hearts and became significantly higher 36 versus 2 days post-MI. Finally, the treatment with an ACE inhibitor (enalaprilat) and a NEP inhibitor (retrothiorphan) in the 36-day infarcted and noninfarcted hearts showed that the relative contribution of ACE in infarcted hearts was comparable with that of noninfarcted hearts, whereas the relative contribution of NEP was increased significantly in infarcted hearts. In conclusion, experimental MI in rats induces complex changes in the metabolism of exogenous BK. The changes resulted in an increased relative contribution of NEP 36 days after infarction.
authors.affiliation: Faculté de Pharmacie, Université de Montréal, C.P 6128, Succursale Centreville, Montréal QC H3C 3J7, Canada.
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Dumoulin
authors.forename: Albert
authors.initials: A
authors.lastname: Adam
authors.forename: Jean-Lucien
authors.initials: JL
authors.lastname: Rouleau
authors.forename: Hugues
authors.initials: H
authors.lastname: Gosselin
authors.forename: Daniel
authors.initials: D
authors.lastname: Lamontagne
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; D001920:Bradykinin