Role of adenosine in ischemic preconditioning in rats depends critically on the duration of the stimulus and involves both A(1) and A(3) receptors

Objectives: There is currently general agreement that adenosine is not invo lved in ischemic preconditioning (IP) in rat hearts. We hypothesized that t he failure to show a role for adenosine is due to the use of brief precondi tioning stimuli, and therefore investigated whether adenosine is involved w hen longer stimuli are employed and which receptor subtypes are involved. M ethods and results: Infarct size (IS) was determined in anesthetized rats a fter 180 min of reperfusion (REP) following a 60-min coronary artery occlus ion (CAO). IS was 69 +/-2% (n=15) of the risk area in control rats and 45 /-2% (n=19; P <0.05) following IP by a single 15-min CAO. The non-selective adenosine receptor antagonist SPT, which itself had no effect on IS (74 +/ -1%), blunted the protection by IP (IS=57 +/-2%, P <0.05) in a dose of 2x5 mg/kg i.v., and abolished the protection (IS=70 +/-1%) at 2x25 mg/kg i.v. F ollowing IP by three cycles of 3-min CAO and 3-min REP, IS was 24 +/-6% (P <0.05), which was not affected by SPT in doses of 2x10 and 2x25 mg/kg i.v. The A(3) antagonist MRS-1191 (3.3 mg/kg, i.p.), which itself did not affect IS (70 +/-2%), blunted the protection by IP with a 15-min CAO (IS=54 +/-2% , P <0.05). When 2x5 mg/kg SPT (a dose selective for A(1)-receptors, as it did not affect the protection by the A(3) selective agonist IB-MECA, 51 +/- 3%) and MRS 1191 were combined the protection by IP was abolished (IS=67 +/ -2%). Conclusions: Involvement of adenosine in IP in rats depends criticall y on the duration of the stimulus. Thus, whereas adenosine was not involved when stimuli of 3-min duration were employed, activation of both A(1) and A(3) receptors contributed when a stimulus of 15 min was used. (C) 2001 Els evier Science B.V. All rights reserved.