Stimulation of adenosine A2b receptors blocks apoptosis in the non-infarcted myocardium even when administered after the onset of infarction.
OBJECTIVE
Chronic adenosine A2b receptor stimulation has been shown to prevent ventricular remodelling after myocardial infarction (MI). We hypothesized that this effect is due to the inhibition of cardiac myocyte apoptosis in the myocardium remote from the infarction.


METHODS
Rats were subjected to MI by LAD ligation in situ. Some animals were pre-treated with the stable adenosine analogue 2-chloro-adenosine (CADO). After 24 h, pro- and anti-apoptotic signals (protein kinase C isoforms, p38, g proteins, Bcl-2/Bax ratio, Akt, Bad), and marker of apoptosis execution (caspase-3, TUNEL) were quantified in the remote myocardium.


RESULTS
CADO prevented the occurrence of apoptosis in the remote myocardium of an infarcted heart. This effect occured not only when CADO was started before the onset of ischemia but also when it started 3 h after the infarction. The anti-apoptotic effect of CADO was blocked by simultaneous administration of the selective adenosine A2b receptor antagonist MRS1754 (1 mg/kg). The anti-apoptotic effect of CADO seems to be mediated by g(alphaq) and by the activation of survival kinases (Bad) and by inhibition of the pro-apoptotic PKC-delta/p38-MAPK-pathway.


CONCLUSIONS
Chronic adenosine A2b receptor stimulation blocks cardiac myocyte apoptosis in the remote myocardium even when started after the onset of infarction. This may explain the anti-remodelling-effect of the A2b receptor stimulation after infarction.
Simonis
Gregor
G
Department of Medicine and Cardiology, Dresden Heart Center, Dresden University of Technology, Germany. gsimonis@gmx.de
Wiedemann
Stephan
S
Joachim
Dirk
D
Weinbrenner
Christof
C
Marquetant
Rainer
R
Strasser
Ruth H
RH
D015762:2-Chloroadenosine / Q000008:administration & dosage; D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D058908:Adenosine A2 Receptor Agonists; D015762:2-Chloroadenosine