Anti-arrhythmic effects of kappa-opioid receptor and its changes in ischemia and reperfusion.
BACKGROUND
It remains unclear whether the kappa-opioid receptor (kappa-OR) is altered during ischemia and reperfusion. Therefore, the present study was designed to investigate changes in the kappa-OR. Additionally, the anti-arrhythmic effect induced by kappa-OR stimulation was also determined during ischemia and reperfusion (I/R).


METHODS
Rats were randomly divided into different groups according to two experimental protocols. The anti-arrhythmic effects of U50,488H, a selective kappa-OR agonist, in an I/R model of 15-min ischemia were studied followed by 15 min of reperfusion. The content of kappa-OR mRNA and protein were measured by RT-PCR and Western blotting techniques in an I/R model of 30-min ischemia followed by 360 min of reperfusion.


RESULTS
Limited numbers of premature ventricular contractions (PVCs) were revealed in the control group. Administration of U50,488H in the control group had no effect on occurrence of PVCs. Incidence of arrhythmia in the I/R group was significantly increased. Treated with U50,488H in the I/R group, the incidence of arrhythmia was significantly reduced. With prior use of nor-BNI, a selective kappa-OR antagonist, the anti-arrhythmic effect of U50,488H was completely blocked. Compared with the control group, the content of kappa-OR mRNA and the density of kappa-OR protein increased significantly at 0 min, 60 min, and 180 min during reperfusion.


CONCLUSIONS
The present study provides evidence for the first time that the expressions of kappa-OR mRNA and protein are upregulated in the heart of I/R rats. This alteration may produce a strengthened anti-arrhythmic effect upon kappa-OR stimulation during I/R.
Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Liu
L
Jin-Cheng
Yin
Y
Wen
Yin
Y
Zhao
Zhang
Z
Quan-Yu
Zhang
Z
Shu-Miao
Guo
G
Hai-Tao
Bi
B
Hui
Wang
W
Yue-Min
Sun
S
Xin
Cheng
C
Liang
Cui
C
Qin
Yu
Y
Shi-Qiang
Alan D
AD
Kaye
Alan
A
Kaye
Yi
Y
Ding-Hua
Pei
P
Jian-Ming
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism*; D015424:Reperfusion
D000889:Anti-Arrhythmia Agents; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer