Abstract
δ-Opioid receptors are known to participate in the protection found following ischemic preconditioning (IPC), but the role of κ-receptors in IPC is currently controversial. Langendorff-perfused rat hearts received 35 min regional ischemia and 2 h reperfusion. PC (2 cycles 5 min global ischemia) substantially reduced infarct size. Pharmacological PC with the δ-agonist DADLE (10 nmol/L) had similar protective effects. However, higher dose DADLE (1 μmol/L) had a less beneficial effect, and in conjunction with the δ-antagonist naltrindole unexpectedly increased infarct size (61.5 ± 2.0%, p < 0.05 v 45.9 ± 2.3% in controls) sugggesting a non-δ effect. The universal κ-opioid agonist bremazocine (30 nmol/L) increased infarct size (61.3 ± 1.6%, p < 0.05 v controls), an effect abrogated by the selective κ1-antagonist nor-binaltorphimine (BNI).
Since opiates are known to have anti-adrenergic effects, which hypothetically may help to mediate IPC, 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), but not in high dose DADLE nor in bremazocine treated hearts.
Thus, in the isolated rat heart κ1-opioid receptor activation exacerbates infarct size through an as yet unknown mechanism, suggesting that there could be an “anti-preconditioned state”. In contrast, δ-activity mediates protection which may be associated with a reduction of tissue cyclic AMP levels.
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Received: 16 November 1999, Accepted: 7 December 1999
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Aitchison, K., Baxter, G., Moneeb Awan, M. et al. Opposing effects on infarction of delta and kappa opioid receptor activation in the isolated rat heart: implications for ischemic preconditioning. Basic Res Cardiol 95, 1–10 (2000). https://doi.org/10.1007/s003950050001
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DOI: https://doi.org/10.1007/s003950050001