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

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 r...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 2008-09, Vol.118 (14 Suppl), p.S32-S37
Main Authors: Xi, Lei, Das, Anindita, Zhao, Zhi-Qing, Merino, Vanessa F, Bader, Michael, Kukreja, Rakesh C
Format: Article
Language:English
Subjects:
Animals
Coronary Circulation
In Vitro Techniques
Ischemic Preconditioning, Myocardial
Male
Mice
Mice, Knockout
Myocardial Contraction
Myocardial Infarction - pathology
Myocardial Reperfusion Injury - prevention & control
Myocardium - metabolism
Receptor, Adenosine A1 - deficiency
Receptor, Adenosine A1 - metabolism
Receptor, Bradykinin B1 - deficiency
Receptor, Bradykinin B1 - metabolism
Receptor, Bradykinin B2 - deficiency
Receptor, Bradykinin B2 - metabolism
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Summary: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. 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%, P0.05). On the other hand, PostC did not significantly alter postischemic cardiac contractile function and coronary flow. 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.
ISSN:0009-7322
1524-4539
DOI:10.1161/CIRCULATIONAHA.107.752865