Extending the cardioprotective window using a novel delta-opioid agonist fentanyl isothiocyanate via the PI3-kinase pathway

Selective delta-opioid agonists produce delayed cardioprotection that lasts for 24-48 h in rats; however, the maximum length of the cardioprotective window is unclear. In this study, we attempted to prolong the cardioprotective window using a unique delta-opioid agonist, fentanyl isothiocyanate (FIT...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2005-06, Vol.288 (6), p.H2744-H2749
Main Authors: Gross, Eric R, Peart, Jason N, Hsu, Anna K, Auchampach, John A, Gross, Garrett J
Format: Article
Language:English
Subjects:
Analgesics, Opioid - pharmacology
Animals
Blood Pressure
Disease Models, Animal
Fentanyl - analogs & derivatives
Fentanyl - pharmacology
Heart Rate
Hemodynamics
Ischemic Preconditioning - methods
Isothiocyanates - pharmacology
Male
Myocardial Infarction - pathology
Myocardial Infarction - physiopathology
Myocardial Infarction - prevention & control
Phosphatidylinositol 3-Kinases - metabolism
Rats
Rats, Sprague-Dawley
Receptors, Opioid, delta - antagonists & inhibitors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Selective delta-opioid agonists produce delayed cardioprotection that lasts for 24-48 h in rats; however, the maximum length of the cardioprotective window is unclear. In this study, we attempted to prolong the cardioprotective window using a unique delta-opioid agonist, fentanyl isothiocyanate (FIT), which binds irreversibly to the delta-receptor, and determined the role of the phosphatidylinositol 3-kinase (PI3K) pathway as a trigger or end effector of FIT-induced cardioprotection. Initially, male rats were administered FIT (10 microg/kg) 10 min before hearts were subjected to 30 min of ischemia and 2 h of reperfusion followed by infarct size (IS) assessment. Acute FIT administration reduced IS when given before ischemia, 5 min before reperfusion, or 10 s after reperfusion compared with control. IS reduction also occurred following a single dose of FIT at 48, 72, 96, and 120 h after administration vs. control, with the maximum effect observed at 96 h. FIT-induced IS reduction at 96 h was completely abolished when the irreversible PI3K inhibitor wortmannin (15 microg/kg) was given before FIT during the trigger phase; however, the effect was only partially abrogated when wortmannin was given 96 h later. These data suggest that FIT has a prolonged cardioprotective window greater than that of any previously described cardioprotective agent that requires PI3K primarily in the trigger phase but also partially, as a mediator or end effector.
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00918.2004