The well-documented age-related change in ischemic tolerance may result from impaired
adenosine-mediated cardioprotection. Additionally,
ischemia itself may potentially modify
adenosine signalling, contributing to the post-ischemic phenotype. This study investigates age- and
ischemia-dependent changes in
adenosine receptor transcript levels (Adora) for the A(1), A(2A), A(2B), and A(3) receptor subtypes in mouse myocardium. Hearts from young (2-4 months) and moderately aged (16-18 months) mice were subjected to 20-min
ischemia and 45-min reperfusion. Ischemic tolerance was impaired in aged hearts, which recovered less than 30% ventricular pressure development (compared with approximately 70% in young hearts), and lost 2-fold higher levels of
lactate dehydrogenase during reperfusion (reflecting cellular disruption). Real-time PCR analyses revealed an age-related decline in Adora3 levels and induction of Adora2B. Curiously, this effect was mimicked by
ischemia, which acutely reduced Adora3 levels and induced Adora2B in young (but not old) hearts. In contrast, in aged hearts
ischemia selectively reduced levels of Adora1 transcript ( approximately 2-fold) without altering transcript levels for the other receptors. These results demonstrate selective modulation of cardioprotective
adenosine receptor transcription by both aging and
ischemia. Reduced A(3)
adenosine receptor transcription may contribute to impaired ischemic tolerance in aged hearts, whereas changes in Adora transcription induced by
ischemia may impact on the post-ischemic phenotype at later time points.