SIGNIFICANCE OF OPIOID, CANNABINOID, BRADYKININ RECEPTORS AND КАТP-CHANNELS IN THE CARDIOPROTECTIVE EFFECT OF ADAPTATION TO COLD

Nikita S. Voronkov, Leonid N. Maslov, Yuri V. Bushov
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Abstract

Highlights It has been shown that chronic adaptation to cold (28 days, +2 – +4°C) has a cardioprotective effect in in vivo model of myocardial ischemia/reperfusion injury in rats. Certain types of receptors and К АТ P -channels might be involved in mechanisms of this effect. Aim . To evaluate the role of opioid, cannabinoid, bradykinin receptors and the К АТ P -channels in the infarct-limiting effect of chronic adaptation to cold. Methods . The study involved male Wistar rats weighing 250–300 g. Rats (two in a cage) were placed in a refrigerator for 28 days. The temperature inside the chamber was +2 – +4 o C. The infarct-limiting effect of chronic adaptation to cold and its possible cancelation by receptor blockers was studied in a 45-minute coronary artery occlusion and a 120-minute reperfusion of the rat myocardium in vivo . The quantitative assessment of myocardial injury was determined by the necrotic zone to the area at risk (NZ/AAR) ratio. Results . We have found that К АТ P -channels are involved in the mechanism of the infarct-limiting effect of chronic adaptation to cold. Opioid, cannabinoid and bradykinin receptors are not involved in this effect. Conclusion . The obtained results have expanded our understanding of cold adaptation, as well as receptor pathways involved in the mechanism of ischemia/reperfusion injury resistance. Further studying of the signaling and receptor pathways of the infarct-limiting effect of cold adaptation will reveal molecules responsible for tolerance to ischemia/reperfusion injury. These molecules can be used to develop novel cardioprotective drugs for the treatment of acute myocardial infarction.
阿片、大麻素、缓激肽受体和КАТp-channels在适应寒冷的心脏保护作用中的意义
研究表明,在大鼠心肌缺血/再灌注损伤的体内模型中,慢性适应寒冷(28天,+2 - +4°C)具有心脏保护作用。某些类型的受体和К АТ P通道可能参与了这种作用的机制。的目标。评价阿片、大麻素、缓激肽受体和К АТ P -通道在慢性适应寒冷的梗死限制作用中的作用。方法。研究对象是体重250-300克的雄性Wistar大鼠。将大鼠(两鼠一笼)置于冰箱中28天。室内温度为+2 ~ +4℃,在大鼠冠脉闭塞45分钟和心肌再灌注120分钟的实验条件下,研究了慢性适应低温对心肌梗死的限制作用及其受体阻滞剂可能的消除作用。以坏死区与危险区(NZ/AAR)之比定量评价心肌损伤程度。结果。我们发现К АТ P通道参与了慢性适应冷的梗死限制作用的机制。阿片、大麻素和缓激素受体不参与这种作用。结论。获得的结果扩大了我们对冷适应的理解,以及参与缺血/再灌注损伤抵抗机制的受体途径。进一步研究冷适应对梗死限制作用的信号通路和受体通路将揭示对缺血/再灌注损伤耐受的分子。这些分子可用于开发治疗急性心肌梗死的新型心脏保护药物。
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