Role of bradykinin in myocardial preconditioning.
The role of bradykinin in the cardioprotective action of ischemic preconditioning was investigated in an anesthetized, open-chest rabbit model of acute coronary occlusion. A branch of the left main coronary artery was reversibly ligated to produce ischemia followed by reperfusion, after which the degree of myocardial necrosis (infarct size as a percent of area at risk) was assessed by tetrazolium staining. Before 30 min of coronary occlusion, rabbits received either ischemic preconditioning (5 min occlusion followed by 10 min reperfusion), no preconditioning, H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH (HOE 140) i.v. (bradykinin receptor antagonist, 1 micrograms/kg) plus preconditioning, HOE 140 alone, a 5-min intra-atrial bradykinin infusion (250 micrograms/kg/min) followed by a 10-min recovery period or HOE 140 plus bradykinin infusion with 10 min recovery. Systemic hemodynamic responses were similar between treatment groups except that both bradykinin infusion groups had a significantly depressed rate of left ventricular pressure development (LV+dP/dtmax) after the 10-min recovery period. Preconditioning reduced infarct size significantly (12 +/- 2%, compared to non-preconditioned controls at 41 +/- 6%), whereas pretreatment with HOE 140 abolished the cardioprotective effect (41 +/- 4%). In addition, bradykinin infusion reduced infarct size significantly (16 +/- 1%), an effect which was also prevented by HOE 140 (41 +/- 5%). HOE 140 alone did not exacerbate the degree of myocardial necrosis (43 +/- 4%). Myocardial area at risk as a percentage of total left ventricular mass was not different between the six treatment groups. The results indicate that endogenously generated bradykinin may mediate the cardioprotective events associated with ischemic preconditioning.
Wall
T M
TM
Cardiovascular Diseases Research Unit, Upjohn Laboratories, Upjohn Company, Kalamazoo, Michigan.
Sheehy
R
R
Hartman
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D011817:Rabbits
C065679:icatibant; D001920:Bradykinin