Ischemic preconditioning and morphine attenuate myocardial apoptosis and infarction after ischemia-reperfusion in rabbits: role of delta-opioid receptor.
نویسندگان
چکیده
We examined whether ischemic preconditioning (IPC) attenuates ischemia-reperfusion injury, in part, by decreasing apoptosis and whether the delta-opioid receptor (DOR) plays a pivotal role in the regulation of apoptosis. Rabbits were subjected to 30-min coronary artery occlusion (CAO) and 180 min of reperfusion. IPC was elicited with four cycles of 5-min ischemia and 10-min reperfusion before CAO. Morphine (0.3 mg/kg iv) was given 15 min before CAO. Naloxone (Nal; 10 mg/kg iv) and naltrindole (Nti; 10 mg/kg iv), the respective nonselective and selective DOR antagonists were given 10 min before either morphine or IPC. Infarct size (%risk area) was reduced from 46 +/- 3.8 in control to 11.6 +/- 1.0 in IPC and 19.5 +/- 3.8 in the morphine group (means +/- SE; P < 0.001 vs. control). Nal blocked the protective effects of IPC and morphine, as shown by the increase in infarct size to 38.6 +/- 7.2 and 44.5 +/- 1.8, respectively. Similarly, Nti blocked IPC and morphine-induced protection. The percentage of apoptotic cells (revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) decreased in IPC (3.6 +/- 1.9) and morphine groups (5.2 +/- 1.2) compared with control group (12.4 +/- 1.6; P < 0.001). Nti pretreatment increased apoptotic cells 11.2 +/- 2.2% in IPC and 12.1 +/- 0.8% in morphine groups. Nal failed to block inhibition of apoptosis in the IPC group (% of cells: 5.7 +/- 1.3 vs. 3.6 +/- 1.9 in IPC alone; P > 0.05). These results were also confirmed by nucleosomal DNA laddering pattern. We conclude that IPC reduces lethal injury, in part, by decreasing apoptosis after ischemia-reperfusion and activation of the DOR may play a crucial role in IPC or morphine-induced myocardial protection.
منابع مشابه
Ischemic preconditioning and morphine attenuate myocardial apoptosis and infarction after ischemia-reperfusion in rabbits: role of -opioid receptor
Okubo, Shinji, Yujirou Tanabe, Kenji Takeda, Michihiko Kitayama, Seiyu Kanemitsu, Rakesh C. Kukreja, and Noboru Takekoshi. Ischemic preconditioning and morphine attenuate myocardial apoptosis and infarction after ischemia-reperfusion in rabbits: role of -opioid receptor. Am J Physiol Heart Circ Physiol 287: H1786–H1791, 2004; 10.1152/ajpheart.01143.2003.—We examined whether ischemic preconditio...
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ورودعنوان ژورنال:
- American journal of physiology. Heart and circulatory physiology
دوره 287 4 شماره
صفحات -
تاریخ انتشار 2004