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Loss of myocardial ischemic postconditioning in adenosine A1 and bradykinin B2 receptors gene knockout mice

Item Type:Article
Title:Loss of myocardial ischemic postconditioning in adenosine A1 and bradykinin B2 receptors gene knockout mice
Creators Name:Xi, L. and Das, A. and Zhao, Z.Q. and Merino, V.F. and Bader, M. and Kukreja, R.C.
Abstract:BACKGROUND: Ischemic postconditioning (PostC) is a recently described cardioprotective modality against reperfusion injury, through series of brief reflow interruptions applied at the very onset of reperfusion. It is proposed that PostC can activate a complex cellular signaling cascade, in which cell membrane receptors could serve as the upstream triggers of PostC. However, the exact subtypes of such receptors remain controversial or uninvestigated. To this context, the purpose of present study was to determine the definitive role of adenosine A(1) and bradykinin B(1) and B(2) receptors in PostC. METHODS AND RESULTS: The hearts isolated from adult male C57BL/6J wild-type mice or the mice lacking adenosine A(1), or bradykinin B(1) or B(2) receptors subjected to zero-flow global ischemia and reperfusion in a Langendorff model. PostC, consisting of 6 cycles of 10 seconds of reperfusion and 10 seconds of ischemia, demonstrated significantly reduced myocardial infarct size (22.8+/-3.1%, mean+/-SEM) as compared with the non-PostC wild-type controls (35.1+/-2.8%, P<0.05). The infarct-limiting protection of PostC was absent in adenosine A(1) receptor knockout mice (34.9+/-2.7%) or bradykinin B(2) receptor knockout mice (33.3+/-1.7%) and was partially attenuated in bradykinin B(1) receptor-deficient mice (25.6+/-2.9%; P>0.05). On the other hand, PostC did not significantly alter postischemic cardiac contractile function and coronary flow. CONCLUSIONS: With the use of three distinctive strains of gene knockout mice, the current study has provided the first conclusive evidence showing PostC-induced infarct-limiting cardioprotection could be triggered by activation of multiple types of cell membrane receptors, which include adenosine A(1) and bradykinin B(2) receptors.
Keywords:Adenosine, Bradykinin, Infarction, Receptors, Reperfusion, Animals, Mice
Publisher:American Heart Association
Number:14 Suppl
Page Range:S32-S37
Date:30 September 2008
Official Publication:https://doi.org/10.1161/CIRCULATIONAHA.107.752865
PubMed:View item in PubMed

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