Enhancement of Na/K pump activity by chronic intermittent hypobaric hypoxia protected against reperfusion injury

Abstract

Chronic intermittent hypobaric hypoxia (CIHH) has been shown to attenuate intracellular Na+ accumulation and Ca2+ 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 Ca2+ 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 α1-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 α1-isoform by 76%, whereas the protein expression of the α2-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 α1-isoform of Na/K pump, which may be one of the mechanisms of CIHH against I/R-induced injury.

Energy metabolism regulated by HDAC inhibitor attenuates cardiac injury in hemorrhagic rat model

“…The integrity of some subcellular structures, particularly the mitochondrial membrane and interior cristae, of cardiomyocytes in animals with massive blood loss were well preserved, as verified by the changes of MMP27, cyt c 2829 and Na-K-ATPase30. In the myocardium, oxidative phosphorylation in the mitochondria is the primary means of ATP synthesis.…”

Lipoxin A4Preconditioning and Postconditioning Protect Myocardial Ischemia/Reperfusion Injury in Rats

“…Meanwhile, Zheng et al [25] found that the protection from cardiac injury may be determined by the Na + -K + -ATPase activity, involving ERK1/2 and PI3 K/Akt signal pathways. Furthermore, continued intermittent hypobaric hypoxia can reduce the reperfusion injury in guinea pig by increasing myocardial Na + -K + -ATPase activity [26]. The Na + -K + -ATPase consists of α and β subunits; the α subunit is responsible for the catalytic activity of the enzyme and includes three isoforms: α 1 , α 2 , and α 3 in the rat heart.…”

Cardiac Response to Chronic Intermittent Hypoxia with a Transition from Adaptation to Maladaptation:The Role of Hydrogen Peroxide

“…It is reported that CIH can induce preconditioning-like effect to effectively protect the heart against ischemia/reperfusion (I/R) or hypoxia/reoxygenation-induced injury [1–6, 8–11, 64, 65], including the prevention of I/R-induced cardiac apoptosis and necrosis [3, 5] arrhythmias [6]. CIH also can improve postischemic recovery of cardiac function [1].…”