Bradykinin B2 receptor is involved in the late phase of preconditioning in rabbit heart.
Activation of bradykinin B2 receptor has been shown to confer short-term cardioprotection against a prolonged ischemic insult. The present study was designed to delineate the role of B2 receptor in the late phase of ischemic preconditioning. Anesthetized, open chest, male rabbits were assigned to 1 of 6 groups (n=8/group). Ischemic preconditioning was elicited by four 5-min occlusion periods interspersed with 10 min of reperfusion. To test the role of B2 receptors, rabbits were pretreated with specific receptor antagonist, HOE-140 (1 microgm/kg IV bolus), 15 min prior to ischemic preconditioning. Additionally, two separate groups of animals were treated by intra-atrial infusion with either bradykinin (0.05 microg/kg/min for 15 min) or saline. Twenty-four hours later, the animals were subjected to 30 min of ischemia and 3 h of reperfusion. Infarct size was determined by tetrazolium staining. Ischemic preconditioning reduced infarct size from 43.09+/-4.66 to 20.65+/-1.87 (% risk area, P<0.05), which was blocked by HOE-140 as indicated by increase in infarct size (36.72+/-4.04%, P<0.05). HOE-140 treatment had no significant effect on infarct size in the sham group. Similarly, intra-atrial infusion of bradykinin caused decrease in the infarct size from 52.36+/-2.17% in the saline control group to 22.83+/-1.71% (P<0.05). The degree of infarct limitation with bradykinin was comparable to ischemic preconditioning (20.65+/-1.87%v 22.83+/-1.71%, P>0.05). For the first time, these results provide evidence for the involvement of B2 receptor in the genesis of late phase of ischemic preconditioning.
Kositprapa
C
C
Division of Cardiology, Department of Medicine, Richmond, VA 23298, USA.
Ockaili
R A
RA
Kukreja
R C
RC
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D065168:Bradykinin Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007261:Infusions, Intra-Arterial / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D011817:Rabbits; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism*; D015424:Reperfusion / Q000379:methods
D065168:Bradykinin Receptor Antagonists; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C065679:icatibant; D001920:Bradykinin