[COX-2 and HO-1 are involved in the delayed preconditioning elicited by bradykinin in rat hearts].
To investigate whether cyclooxygenase-2 (COX-2) and heme oxygenase-1 (HO-1) are involved in the bradykinin-induced delayed protection.



Cardiac contractility, lactate dehydrogenase (LDH) and infarct area were analyzed in isolated rat hearts undergoing ischemia-reperfusion injury induced by Langendorff method.



Conscious rats received bradykinin (40 microg/kg), and the isolated hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion 24 h later. Bradykinin pretreatment would improve post-ischemic performance, and reduced the release of LDH and infarct size. COX-2 inhibitor celecoxib (3 mg/kg) abolished bradykinin-induced protection, leading to poorer myocardial performance, release of more LDH and larger infarct sizes. Administration of HO-1 inhibitor ZnPP IX(20 microg/kg) before bradykinin partially abrogated the delayed protection. Pretreatment with the mitochondrial ATP sensitive potassium channel(mitoK(ATP) antagonist 5-HD before or 24 h after bradykinin administration also abolished the effect of protection.



The results indicate that activation of HO-1 and COX-2 might be involved in the delayed cardioprotection evoked by bradykinin, and mitoK(ATP) channel may serve as both a trigger and a mediator in the cardioprotection.
Dong
Hai-Zheng
HZ
Department of Physiology, College of Medicine, Zhejiang University, Hangzhou 310058, China.
Chen
Ying-Ying
YY
Zhu
Li
L
Xu
He-Jing
HJ
Wang
Yang
Y
Shen
Fa-Rong
FR
Cai
Zhu-Nan
ZN
Shen
Yue-Liang
YL
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D015221:Potassium Channels / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D015221:Potassium Channels; D011720:Pyrazoles; D013449:Sulfonamides; C117780:mitochondrial K(ATP) channel; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D001920:Bradykinin