E. Kodani et al., Protection of IB-MECA against myocardial stunning in conscious rabbits is not mediated by the A(1) adenosine receptor, BAS R CARD, 96(5), 2001, pp. 487-496
The goal of this study was to determine whether the protective effects of t
he A(3)AR agonist N-6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-ME
CA) against myocardial stunning are mediated by the AAR. Six groups of cons
cious rabbits underwent a sequence of six 4-minute coronary occlusion (O)/4
-minute reperfusion (R) cycles for three consecutive days (days 1, 2, and 3
). In vehicle-treated rabbits (group I), the recovery of systolic wall thic
kening (WTh) in the ischemic/reperfused region was markedly depressed on da
y 1, indicating the presence of severe myocardial stunning. On days 2 and 3
, however, the recovery of systolic WTh was markedly accelerated, indicatin
g the presence of late ischemic preconditioning (PC). When rabbits were pre
treated with the A,AR agonist 2-chloro-N-6-cyclopentyladenosine (CCPA, 100
mug/kg i.v.) or with IB-MECA (100 mug/kg i.v.) 10 min prior to the first se
quence of O/R cycles on day 1 (group III and V, respectively), the recovery
of systolic WTh was markedly accelerated compared to vehicle-treated anima
ls (reflected as an similar to 48 % decrease in the total deficit of systol
ic WTh). The magnitude of the protection afforded by adenosine receptor ago
nists was equivalent to that provided by late ischemic PC. Pre-treating rab
bits with the A(1)AR antagonist N-0861 completely blocked both the hemodyna
mic and the cardioprotective effects of CCPA (group IV). However, the same
dose of N-0861 did not block the cardioprotective actions of IB-MECA (group
VI). Importantly, N-0861 did not influence the degree of myocardial stunni
ng in the absence of PC (group II) and it did not block the development of
late ischemic PC. Taken together, these results provide conclusive evidence
that the cardioprotective effects of IB-MECA are not mediated via the A(1)
AR, supporting the concept that activation of A(3)ARs prior to an ischemic
challenge provides protection against ischemia/reperfusion injury.