Bradykinin elicits "second window" myocardial protection in rat heart through an NO-dependent mechanism.
Bradykinin is an important endogenous mediator exerting acute protective effects in the ischemic myocardium. The aims of this study were to investigate whether exogenously administered bradykinin could evoke delayed myocardial protection and to determine whether any protection observed might be dependent on nitric oxide (NO) generation. Conscious rats received bradykinin (40 microg/kg iv) or saline, preceded 15-20 min earlier by the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg ip) or saline. Twenty-four hours later, hearts were Langendorff perfused and subjected to 35 min of regional ischemia and 120 min of reperfusion. Infarct size was assessed using tetrazolium staining and expressed as a percentage of the risk zone. Bradykinin pretreatment reduced the infarct-to-risk ratio from 53.5 +/- 3.2% to 29.1 +/- 4.7% (P < 0.01). The administration of L-NAME before bradykinin abrogated the delayed protection (infarct size 52.3 +/- 5.0%) but alone did not influence infarct size (53.5 +/- 4.8%). These results are the first to demonstrate that bradykinin can evoke a delayed ("second window") enhancement of myocardial tolerance to ischemia, an action that is dependent on the early generation of NO.
Ebrahim
Z
Z
The Hatter Institute, University College London, London WC1E 6DB, United Kingdom.
Yellon
D M
DM
Baxter
G F
GF
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage*; D003326:Coronary Circulation; D003327:Coronary Disease / Q000150:complications; D019610:Cytoprotection / Q000187:drug effects*; D004334:Drug Administration Schedule; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester