Department of Pharmacology and Pharmacotherapy, University of Szeged, H-6721 Szeged, Hungary.
MTA-SZTE Research Group of Cardiovascular Pharmacology, H-6721 Szeged, Hungary.
Int J Mol Sci. 2019 Nov 13;20(22):5687. doi: 10.3390/ijms20225687.
We have evidence that the intravenous infusion of sodium nitrite (NaNO) results in an antiarrhythmic effect when given 24 h prior to an ischemia and reperfusion (I/R) insult in anaesthetized dogs. This protection was associated with the reduction of reactive oxygen species resulting from I/R through the attenuation of mitochondrial respiration. Here, we examined whether the changes in calcium, which also contributes to arrhythmia generation, play a role in the NaNO-induced effect. On the first day, 30 anaesthetized dogs were treated either with saline or NaNO (0.2 µmol/kg/min) for 20 min. Some animals were subjected to a 25 min LAD (anterior descending branch of the left coronary artery) occlusion and 2 min reperfusion (I/R = 4; NaNO-I/R = 6), or the heart was removed 24 h later. We have shown that nitrite prevented the I/R-induced increase in cellular and mitochondrial calcium deposits. During simulated I/R, the amplitude of the calcium transient and the diastolic calcium level were significantly lower in the nitrite-treated hearts and the ERP (effective refractory period) fraction of the action potential was significantly increased. Furthermore, nitrite also enhanced the mitochondrial respiratory response and prevented the MPTPT opening during calcium overload. These results suggest that nitrite can reduce the harmful consequences of calcium overload, perhaps directly by modulating ion channels or indirectly by reducing the mitochondrial ROS (reactive oxygen species) production.
我们有证据表明，在麻醉犬中，在缺血再灌注（I/R）损伤前 24 小时静脉输注亚硝酸钠（NaNO）可导致抗心律失常作用。这种保护作用与 I/R 引起的活性氧减少有关，通过抑制线粒体呼吸来实现。在这里，我们研究了钙的变化是否在 NaNO 诱导的作用中起作用，钙的变化也有助于心律失常的发生。在第一天，30 只麻醉犬接受生理盐水或 NaNO（0.2 µmol/kg/min）治疗 20 分钟。一些动物接受 25 分钟 LAD（左冠状动脉前降支）闭塞和 2 分钟再灌注（I/R = 4；NaNO-I/R = 6），或 24 小时后取出心脏。我们已经表明，亚硝酸盐可防止 I/R 引起的细胞和线粒体钙沉积增加。在模拟 I/R 期间，亚硝酸盐处理的心脏中钙瞬变的幅度和舒张期钙水平明显降低，动作电位的 ERP（有效不应期）分数明显增加。此外，亚硝酸盐还增强了线粒体呼吸反应，并防止了钙超载期间 MPTPT 的开放。这些结果表明，亚硝酸盐可以减轻钙超载的有害后果，可能是通过直接调节离子通道，也可能是通过减少线粒体 ROS（活性氧）的产生。
