Anti-arrhythmic Effects of κ-Opioid Receptor and Its Changes in Ischemia and Reperfusion

Jin-Cheng, Liu; Wen, Yin; Zhao, Yin; Quan-Yu, Zhang; Shu-Miao, Zhang; Hai-Tao, Guo; Hui, Bi; Yue-Min, Wang; Xin, Sun; Liang, Cheng; Qin, Cui; Shi-Qiang, Yu; Kaye, Alan; Ding-Hua, Yi; Jian-Ming, Pei

doi:10.1016/j.arcmed.2008.02.011

« Previous Next »Archives of Medical Research
Volume 39, Issue 5 , Pages 483-488, July 2008

Anti-arrhythmic Effects of κ-Opioid Receptor and Its Changes in Ischemia and Reperfusion

Liu Jin-Cheng
- Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
- Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Yin Wen
- Department of Emergency, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Yin Zhao
- Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Zhang Quan-Yu
- Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Zhang Shu-Miao
- Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Guo Hai-Tao
- Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Bi Hui
- Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Wang Yue-Min
- Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Sun Xin
- Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Cheng Liang
- Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Cui Qin
- Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Yu Shi-Qiang
- Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Alan Kaye
- Department of Anesthesiology and Department of Pharmacology, LSU School of Medicine, New Orleans, Louisiana
Yi Ding-Hua
- Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
Pei Jian-Ming
- Department of Physiology, National Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
- Department of Cardiac Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China
- Address reprint requests to: Pei Jian-Ming, Fourth Military Medical University, Department of Physiology, No.169, West Changle Road, Xi'an, Shaanxi Province 710032; China

Received 5 January 2008; accepted 21 February 2008.

(ARCMED-D-08-00007)

Background

It remains unclear whether the κ-opioid receptor (κ-OR) is altered during ischemia and reperfusion. Therefore, the present study was designed to investigate changes in the κ-OR. Additionally, the anti-arrhythmic effect induced by κ-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 κ-OR agonist, in an I/R model of 15-min ischemia were studied followed by 15 min of reperfusion. The content of κ-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 κ-OR antagonist, the anti-arrhythmic effect of U50,488H was completely blocked. Compared with the control group, the content of κ-OR mRNA and the density of κ-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 κ-OR mRNA and protein are upregulated in the heart of I/R rats. This alteration may produce a strengthened anti-arrhythmic effect upon κ-OR stimulation during I/R.

Key Words: Ischemia/reperfusion, κ-Opioid Receptor, Arrhythmia, U50,488H