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.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. ggross@mcw.edu
Garrett J
GJ
Gross
Anna
A
Hsu
Kasem
K
Nithipatikom
Adam W
AW
Pfeiffer
Irina
I
Bobrova
Erik
E
Bissessar
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003652:Decanoic Acids / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology / Q000627:therapeutic use*; D006880:Hydroxy Acids / Q000494:pharmacology; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists
D001549:Benzamides; D002316:Cardiotonic Agents; D003652:Decanoic Acids; D004745:Enkephalins; D006880:Hydroxy Acids; D054086:KATP Channels; D026902:Potassium Channel Blockers; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C557293:eribis peptide 94; D009569:Nitric Oxide; C052853:5-hydroxydecanoic acid; C410297:HMR 1098; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat