The purpose of this study was to determine if the cardioprotective effect of
adenosine on the ischemic myocardium is mediated by interaction with specific
adenosine receptor subtypes. Isolated rat hearts perfused at constant flow were subjected to global normothermic (37 degrees C)
ischemia and the time to onset of
ischemic contracture (TOIC) was used as a marker of myocardial ischemic injury. Hearts treated with
adenosine and R-
phenylisopropyladenosine (PIA), an
adenosine A1 receptor agonist, exhibited a significantly greater TOIC than control hearts (18.60 +/- 0.40 and 16.64 +/- 1.15 min, respectively vs 9.12 +/- 0.66 min), whereas phenylaminoadenosine, an
adenosine A2 receptor agonist, had no effect on TOIC (11.73 +/- 0.87 min).
BW A1433U, an
adenosine receptor antagonist, blocked the effects of
adenosine and PIA on
ischemic contracture time, and
BW A1433U did not alter the ability of
nifedipine or
propranolol to delay the onset of
ischemic contracture, thus indicating the specificity of this compound for the
adenosine receptor. PIA-treated hearts exhibited significantly greater
ATP levels throughout the ischemic period compared to control hearts, whereas hearts treated with
BW A1433U showed a rapid decline in
ATP content. These results suggest that the beneficial effects of
adenosine on the ischemic myocardium are mediated by interaction with
adenosine A1 receptors, and that endogenously formed
adenosine plays a role in attenuating myocardial ischemic damage.