Pharmacological postconditioning of the rabbit heart with non-selective, A1 , A2A and A3 adenosine receptor agonists.
OBJECTIVE
We investigated the effects of novel selective and non-selective adenosine receptor agonists (ARs) on cardioprotection.


METHODS
Male rabbits divided into six groups were subjected to 30-min heart ischaemia and 3-h reperfusion: (1) control group, (2) postconditioning (PostC) group, (3) group A: treated with the non-selective agonist (S)-PHPNECA, (4) group B: treated with the A1 agonist CCPA, (5) group C: treated with the A2A agonist VT 7 and (6) group D: treated with the A3 agonist AR 170. The infarcted (I) and the areas at risk (R) were estimated as %I/R. In additional rabbits of all groups, heart samples were taken for determination of Akt, eNOS and STAT 3 at the 10th reperfusion minute.


RESULTS
(S)-PHPNECA and CCPA reduced the infarct size (17.2 ± 2.9% and 17.9 ± 2.0% vs 46.8 ± 1.9% in control, P < 0.05), conferring a benefit similar to PostC (26.4 ± 0.3%). Selective A2A and A3 receptor agonists did not reduce the infarct size (39.5 ± 0.8% and 38.7 ± 3.5%, P = NS vs control). Akt, eNOS and STAT 3 were significantly activated after non-selective A1 ARs and PostC.


CONCLUSIONS
Non-selective and A1 but not A2A and A3 ARs agonists are essential for triggering cardioprotection. The molecular mechanism involves both RISK and the JAK/STAT pathways.
Department of Pharmaceutical Chemistry, University of Athens School of Pharmacy, Athens, Greece.
Sophia-Iris
SI
Bibli
Efstathios K
EK
Iliodromitis
Catia
C
Lambertucci
Anastasia
A
Zoga
Nikolaos
N
Lougiakis
Nikolaos
N
Dagres
Rosaria
R
Volpini
Diego
D
Dal Ben
Dimitrios Th
DT
Kremastinos
Anna
A
Tsantili Kakoulidou
Gloria
G
Cristalli
Ioanna
I
Andreadou
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology*; D011817:Rabbits; D011983:Receptors, Purinergic / Q000378:metabolism*
D002316:Cardiotonic Agents; D058906:Purinergic P1 Receptor Agonists; D011983:Receptors, Purinergic
RISK and JAK/STAT pathways; adenosine receptor agonists; infarct size; postconditioning