Previous results from our laboratory have suggested that morphine can attenuate neutrophil activation in patients with acute myocardial infarction. To elucidate if morphine preconditioning (PC) has the same effects via activation of neutrophil endopeptidase 24.11 (NEP), we measured serum levels of intercellular adhesion molecule-1 (ICAM-1), gp100(MEL14) and NEP in adult Wistar rats subjected to ten different protocols (n=10 for each) at baseline, immediately after and 2 h after morphine PC. All groups were subjected to 30 min of occlusion and 2 h of reperfusion. Similarly, morphine-induced PC was elicited by 3-min drug infusions (100 μg/kg) interspersed with 5-min drug- free periods before the prolonged 30-min occlusion. Infarct size (IS), as a percentage of the area at risk (AAR), was determined by triphenyltetrazolium staining. Pretreatment with morphine increased NEP activities (9.86±1.98 vs. 5.12±1.10 nmol/mg protein in control group; p<0.001). Naloxone (μ-opioid receptor antagonist) (4.82±1.02 nmol/mg protein) and phosphoramidon (NEP inhibitor) (4.66±1.00 nmol/mg protein) inhibited morphine-activated NEP, whereas glibenclamide (ATP-sensitive potassium channel antagonist) and chelerythrine (protein kinase C inhibitor) had no effects. The ICAM-1 and gp100(MEL14) of the third sampling were lowest for those with morphine PC (280±30 ng/ml and 2.2±0.7 μg/ml; p<0.001), but naloxone (372±38 ng/ml and 3.8±0.9 μg/ml) and phosphoramidon (382±40 ng/ml and 4.2±1.1 μg/ml) abolished the above phenomenon. IS/AAR were definitely lowest for those with morphine PC (24±7%; p<0.05). Morphine preconditioning increases NEP activities to attenuate shedding of gp100(MEL14) and to ICAM-1 and, thus, provides myocardial protection.
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