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


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.
Xi
Lei
L
Division of Cardiology, Box 980204, Virginia Commonwealth University, 1101 East Marshall Street, Room 7-042, Richmond, VA 23298-0204, USA. lxi@vcu.edu
Das
Anindita
A
Zhao
Zhi-Qing
ZQ
Merino
Vanessa F
VF
Bader
Michael
M
Kukreja
Rakesh C
RC
D000818:Animals; D003326:Coronary Circulation; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000172:deficiency / Q000378:metabolism*; D043783:Receptor, Bradykinin B1 / Q000172:deficiency / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000172:deficiency / Q000378:metabolism*
D043682:Receptor, Adenosine A1; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2