Preischemic bradykinin and ischaemic preconditioning in functional recovery of the globally ischaemic rat heart.
OBJECTIVE
Substantial release of bradykinin has been demonstrated to occur during short periods of myocardial ischaemia in various species. The aim of the present study was to investigate the protective effect of bradykinin in ischaemia and whether bradykinin could be involved in ischaemic preconditioning in the rat heart.


METHODS
Isolated, buffer-perfused hearts were subjected to 30 min of global ischaemia, followed by 30 min of reperfusion. Postischaemic functional recovery was recorded in the following groups: (1) control; (2) treatment with 0.1 microM bradykinin for 10 min before ischaemia (BK); (3) bradykinin treatment combined with pretreatment with the specific bradykinin B2-receptor antagonist, HOE 140; (4) ischaemic preconditioning by 5 min ischaemia +5 min reperfusion prior to sustained ischaemia (i.p.); and (5) ischaemic preconditioning combined with HOE 140 administration.


RESULTS
Postischaemic myocardial function was significantly improved in both BK and i.p. groups (developed pressure 66.9 +/- 6.8 and 67.6 +/- 7.1 mmHg, respectively, vs. 43.1 +/- 5.9 mmHg in controls, P < 0.05). Pretreatment with 1 microM HOE 140 completely abolished the effect of bradykinin, while protection achieved by i.p. was unaltered by this drug. None of the protective interventions was associated with any significant improvement in myocardial adenosine triphosphate, creatine phosphate, glycogen, lactate or glucose tissue levels, detected either at the end of ischaemia or after 30 min of reperfusion.


CONCLUSIONS
Bradykinin, acting via B2-receptors, can protect against postischaemic contractile dysfunction to a similar extent as i.p.. An involvement of B2-receptors in the ischaemic preconditioning phenomenon could, however, not be demonstrated.
Starkopf
J
J
Department of Biochemistry, Faculty of Medicine, University of Tartu, Estonia. joels@fagmed.uit.no
Bugge
E
E
Ytrehus
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D065168:Bradykinin Receptor Antagonists; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D065168:Bradykinin Receptor Antagonists; D010725:Phosphocreatine; D019344:Lactic Acid; C065679:icatibant; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose; D001920:Bradykinin