Dept. of Pharmacology, Hebei Medical Univ., 361 East Zhongshan Road, Shijiazhuang 050017, Hebei Province, China.
Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2280-7. doi: 10.1152/ajpheart.01164.2010. Epub 2011 Mar 25.
Chronic intermittent hypobaric hypoxia (CIHH) has been shown to attenuate intracellular Na(+) accumulation and Ca(2+) overload during ischemia and reperfusion (I/R), both of which are closely related to the outcome of myocardial damage. Na/K pump plays an essential role in maintaining the equilibrium of intracellular Na(+) and Ca(2+) during I/R. It has been shown that enhancement of Na/K pump activity by ischemic preconditioning may be involved in the cardiac protection. Therefore, we tested whether Na/K pump was involved in the cardioprotection by CIHH. We found that Na/K pump current in cardiac myocytes of guinea pigs exposed to CIHH increased 1.45-fold. The K(1) and f(1), which reflect the portion of α(1)-isoform of Na/K pump, dramatically decreased or increased, respectively, in CIHH myocytes. Western blot analysis revealed that CIHH increased the protein expression of the α(1)-isoform by 76%, whereas the protein expression of the α(2)-isoform was not changed significantly. Na/K pump current was significantly suppressed in simulated I/R, and CIHH preserved the Na/K pump current. CIHH significantly improved the recovery of cell length and contraction during reperfusion. Furthermore, inhibition of Na/K pump by ouabain attenuated the protective effect afforded by CIHH. Collectively, these data suggest that the increase of Na/K pump activity following CIHH is due to the upregulating α(1)-isoform of Na/K pump, which may be one of the mechanisms of CIHH against I/R-induced injury.
慢性间歇性低氧（CIHH）已被证明可减轻缺血再灌注（I/R）期间的细胞内 Na(+)积累和 Ca(2+)超载，这两者都与心肌损伤的结果密切相关。Na/K 泵在 I/R 期间对维持细胞内 Na(+)和 Ca(2+)的平衡起着至关重要的作用。已经表明，通过缺血预处理增强 Na/K 泵的活性可能与心脏保护有关。因此，我们测试了 CIHH 是否通过 Na/K 泵参与了心脏保护。我们发现，暴露于 CIHH 的豚鼠心肌细胞中的 Na/K 泵电流增加了 1.45 倍。反映 Na/K 泵α(1)-同工型的 K(1)和 f(1)分别显著降低或增加。Western blot 分析显示，CIHH 使α(1)-同工型的蛋白表达增加了 76%，而α(2)-同工型的蛋白表达则没有明显变化。在模拟 I/R 中，Na/K 泵电流明显受到抑制，而 CIHH 则保留了 Na/K 泵电流。CIHH 显著改善了再灌注期间细胞长度和收缩的恢复。此外，哇巴因抑制 Na/K 泵会削弱 CIHH 提供的保护作用。总的来说，这些数据表明，CIHH 后 Na/K 泵活性的增加是由于 Na/K 泵α(1)-同工型的上调，这可能是 CIHH 对抗 I/R 诱导损伤的机制之一。
