Kappa-opioid receptor agonist protects the microcirculation of skeletal muscle from ischemia reperfusion injury.
BACKGROUND
Previous research has demonstrated that pretreatment with kappa opioid receptor (KOR) agonist protects against ischemia reperfusion (I/R) injury in cardiomyocytes and neuron cells through activation of protein kinase C. The purpose of this study is to investigate the KOR agonist's effect on I/R-injured cremaster muscle and its underlying mechanism.


METHODS
Male Sprague Dawley rats were randomized into 3 groups (n = 6 each group). Group I was the ischemia reperfusion (I/R) injury group (4 hours of ischemia followed by 90 minutes of reperfusion). Group II was the U-50488H (selective KOR agonist)-pretreated group (KOR agonist + I/R injury). Group III was pretreated with U-50488H + nor-binaltorphimine (NBI, a selective KOR antagonist) (KOR agonist + antagonist + I/R injury). The numbers of leukocyte rolling, adhering, and transmigrating, functional capillary, and swelling index of the vessel wall of the postcapillary venule were observed under intravital videomicroscopy. Biochemically, the lactate dehydrogenase, creatine phosphokinase isoenzyme, expression of E-selectin, and intercellular adhesion molecule-1 (ICAM-1) were analyzed.


RESULTS
The U-50488H-pretreated group had significantly decreased the number of leukocyte sticking (P < 0.001) and transmigrating (P < 0.001) as compared with the I/R-injury group and the U-50488H + NBI-pretreated group. The numbers of functional capillary in the U-50488H-pretreated group were significantly less attenuated compared with the I/R-injury group and U-50488H + NBI-pretreated group (P < 0.001). The expression of the ICAM-1 in the cremaster muscle was evidently reduced in the U-50488H-pretreated group than in the I/R-injury group or the U-50488H + NBI-pretreated group.


CONCLUSIONS
Administration of KOR agonist protects the muscle flap microcirculation from I/R injury, which can be abolished by concomitant KOR antagonist administration. The KOR agonist-induced protection from ischemia reperfusion injury may be related to decreased expression of adhesion molecule ICAM-1.
Lin
Jeng-Yee
JY
Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
Hung
Li-Man
LM
Lai
Lingo Yiling
LY
Wei
Fu-Chan
FC
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007511:Ischemia / Q000517:prevention & control*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000517:prevention & control; D013524:Surgical Flaps / Q000098:blood supply*
D017473:Receptors, Opioid, kappa; D018799:Intercellular Adhesion Molecule-1; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer