The infarct size-limiting effect elicited by cold acclimation (CA) is accompanied by increased mitochondrial resistance and unaltered β₁-adrenergic receptor (AR) signaling persisting for two weeks at room temperature. As the mechanism of CA-elicited cardioprotection is not fully understood we examined the role of the salvage β₂-AR/Gi/Akt pathway. Male Wistar rats were exposed to CA (8 °C, 5 weeks), while the recovery group (CAR) was kept at 24 °C for additional 2 weeks. We show that the total number of myocardial β-ARs in the left ventricular myocardium did not change after CA but decreased after CAR. We confirmed the infarct size-limiting effect in both CA and CAR groups. Acute administration of β₂-AR inhibitor ICI-118551 abolished the protective effect in the CAR group but had no effect in the control and CA groups. The inhibitory Giα1/2 and Giα3 proteins increased in the membrane fraction of the CAR group, and the p-Akt^Ser473/Akt ratio also increased. Expression, phosphorylation, and mitochondrial location of the Akt target glycogen synthase kinase (GSK3β), were affected neither by CA nor by CAR. However, GSK3β translocated from the Z-disc to the H-zone after CA, and acquired its original location after CAR. Our data indicate that the cardioprotection observed after CAR is mediated by the β_2-AR/Gi pathway and Akt activation. Further studies are needed to unravel downstream targets of the central regulators of the CA process and the downstream targets of the Akt protein after CAR.

中文翻译：

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β2肾上腺素受体途径和Akt激活介导冷适应过程中持久的心脏保护作用

由冷驯化（CA）引发的梗塞大小限制作用是伴随着增加线粒体性和未改变的β ₁ -肾上腺素能受体（AR）信令在室温下持续两周。作为CA诱发心肌保护的机制尚不完全清楚，我们检查了打捞β的作用₂ -AR / GI / Akt信号通路。将Wistar雄性大鼠暴露于CA（8°C，5周），而恢复组（CAR）在24°C下再保持2周。我们显示，CA后左心室心肌中β-AR的总数没有变化，而在CAR后减少。我们证实了CA和CAR组均存在梗塞大小限制作用。β急性管理₂-AR抑制剂ICI-118551消除了CAR组的保护作用，但对对照组和CA组没有作用。CAR组的膜部分抑制性Giα1/ 2和Giα3蛋白增加，p-Akt ^Ser473 / Akt比也增加。Akt靶糖原合酶激酶（GSK3β）的表达，磷酸化和线粒体位置不受CA和CAR的影响。然而，GSK3β在CA后从Z盘转移到H区，并在CAR后获得其原始位置。我们的数据表明CAR由β介导后的心脏保护观察_2-AR / Gi途径和Akt激活。需要进一步研究以阐明CA过程中中央调节剂的下游靶标和CAR后Akt蛋白的下游靶标。