COX-2 and HO-1 are involved in the delayed preconditioning elicited by bradykinin in rat hearts.
- Author:
Hai-Zheng DONG
1
;
Ying-Ying CHEN
;
Li ZHU
;
He-Jing XU
;
Yang WANG
;
Fa-Rong SHEN
;
Zhu-Nan CAI
;
Yue-Liang SHEN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Bradykinin; pharmacology; Celecoxib; Cyclooxygenase 2; metabolism; Cyclooxygenase Inhibitors; pharmacology; Heme Oxygenase-1; metabolism; In Vitro Techniques; Ischemic Preconditioning, Myocardial; methods; Male; Myocardial Reperfusion Injury; enzymology; prevention & control; Potassium Channels; physiology; Pyrazoles; pharmacology; Random Allocation; Rats; Rats, Sprague-Dawley; Sulfonamides; pharmacology
- From: Journal of Zhejiang University. Medical sciences 2007;36(1):13-20
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate whether cyclooxygenase-2 (COX-2) and heme oxygenase-1 (HO-1) are involved in the bradykinin-induced delayed protection.
METHODSCardiac contractility, lactate dehydrogenase (LDH) and infarct area were analyzed in isolated rat hearts undergoing ischemia-reperfusion injury induced by Langendorff method.
RESULTConscious 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.
CONCLUSIONThe 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.
