title: Bradykinin degradation and relation to myocyte contractility.
abstract: BACKGROUND
  Past studies have demonstrated that exogenous bradykinin (BK) causes vasodilation and increases coronary blood flow, effects that may be beneficial in the setting of cardiac disease states. An important pathway for BK degradation is through angiotensin-converting enzyme (ACE), which results in the formation of a degradative peptide, BK((1-7)). The goal of this study was to examine the effects of BK, BK((1-7)), and the potential modulation of BK by ACE inhibition on myocyte contractility.
  
  
  RESULTS
  Contractile function was examined in isolated adult porcine (n = 15) left ventricular (LV) myocyte preparations in the presence or absence of BK (10(-8) mol/L), BK((1-7)) (10(-8) mol/L), and with pretreatment by ACE inhibition (benazaprilat). Myocyte velocity of shortening fell by over 15% in the presence of BK and by 8% with BK((1-7)) (P <.05 vs basal). ACE inhibition blunted the negative effect of BK on myocyte velocity of shortening by over 60% (P <.05). Furthermore, robust ACE activity coupled with significant BK degradation was demonstrated in LV-isolated myocyte preparations, and BK proteolysis was influenced by ACE inhibition.
  
  
  CONCLUSIONS
  These results suggest that BK has a direct effect on LV myocyte contractility, and that this effect may be mediated by proteolysis of BK at the level of the LV myocyte sarcolemma.
authors.affiliation: Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Krombach
authors.forename: J H
authors.initials: JH
authors.lastname: McElmuray
authors.forename: D M
authors.initials: DM
authors.lastname: Gay
authors.forename: M J
authors.initials: MJ
authors.lastname: Clair
authors.forename: R
authors.initials: R
authors.lastname: Mukherjee
authors.forename: A T
authors.initials: AT
authors.lastname: Goldberg
authors.forename: S C
authors.initials: SC
authors.lastname: Baicu
authors.forename: F G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D013552:Swine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001920:Bradykinin