Acute and chronic cardioprotection by the enkephalin analogue, Eribis peptide 94, is mediated via activation of nitric oxide synthase and adenosine triphosphate-regulated potassium channels.

Eribis peptide 94 (EP 94) is a new enkephalin derivative which potently binds to the µ- and δ-opioid receptor. In this study, we determined the effects of EP 94 and potential mechanism(s) involved in cardioprotection of the rat heart. An acute (5 and10 min into ischemia) and a chronic (24 h prior to ischemia) EP 94 administration produced a similar 30-40% reduction in infarct size/area at risk and the effects were blocked by the K(ATP) channel antagonists, HMR 1098 and 5-HD. The cardioprotective effects were blocked by a nonselective nitric oxide synthase (NOS) inhibitor (L-NAME) following acute administration and by a selective iNOS inhibitor (1400W) following chronic administration. These results suggest that EP 94 may have potential for the treatment of ischemic heart disease via a nitric oxide (NO)-K(ATP)-mediated mechanism.