Opposing effects on infarction of delta and kappa opioid receptor activation in the isolated rat heart: implications for ischemic preconditioning

delta-Opioid receptors are known to participate in the protection found fol lowing ischemic preconditioning (IPC), but the role of kappa-receptors in I PC is currently controversial. Langendorff-perfused rat hearts received 35 min regional ischemia and 2 h reperfusion. PC (2 cycles 5 min global ischem ia) substantially reduced infarct size. Pharmacological PC with the delta-a gonist DADLE (10 nmol/L) had similar protective effects. However, higher do se DADLE (1 mu mol/L) had a less beneficial effect, and in conjunction with the delta-antagonist naltrindole unexpectedly increased infarct size (61.5 +/- 2.0 %, p<0.05 v 45.9 +/- 2.4 % in controls) suggesting a non-delta eff ect. The universal kappa-opioid agonist bremazocine (30 nmol/L) increased i nfarct size (61.3 +/- 1.6 %, p<0.05 v controls), an effect abrogated by the selective kappa(1)-antagonist nor-binaltorphimine (BNI). Since opiates are known to have anti-adrenergic effects, which hypothetical ly may help to mediate LPC, cyclic AMP levels were measured in DADLE and in bremazocine-treated hearts. Decreased levels of cyclic AMP at the start of the regional ischemic period were found in low dose DADLE hearts (0.485 +/ - 0/020, n = 8, vs controls, 0.654 +/- 0.025 nmol/g wet weight, p<0.001), b ut not in high dose DADLE nor in bremazocine treated hearts. Thus, in the isolated rat heart kappa(1)-opioid receptor activation exacerb ates infarct size through an as yet unknown mechanism, suggesting that ther e could be an "anti-preconditioned state". In contrast, delta-activity medi ates protection which may be associated with a reduction of tissue cyclic A MP levels.