Iwamoto Takahiro
Fukuoka University, Department of Pharmacology, School of Medicine, Jonan-ku, Fukuoka 814-0180, Japan.
Future Cardiol. 2005 Jul;1(4):519-29. doi: 10.2217/14796678.1.4.519.
Intracellular calcium ions (Ca2+) are the key regulators in cardiac and arterial functions during the contraction-relaxation cycle. Myocyte Ca2+ imbalance thus produces mechanical dysfunction, electrical instability (arrhythmia) and muscle remodeling. The sodium-calcium exchanger (NCX) is one of the major Ca(2+)-handling proteins in myocytes. Evidence is currently accumulating to suggest that NCX1 is upregulated in various cardiovascular diseases. Recently developed benzyloxyphenyl NCX inhibitors effectively prevent myocardial ischemia/reperfusion injury and salt-sensitive hypertension in animal models. Furthermore, several experiments with genetically engineered mice provide compelling evidence that these diseases are triggered by pathologic Ca2+ entry through NCX1 in cardiac and arterial myocytes, respectively. Thus, NCX inhibitors may have therapeutic potential as novel cardiovascular drugs for myocardial reperfusion injury and salt-sensitive hypertension. However, the efficacy of NCX inhibitors, as well as the role of NCX1, in heart failure or arrhythmias requires more detailed study.
细胞内钙离子（Ca2+）是心脏和动脉在收缩 - 舒张周期中功能的关键调节因子。因此，心肌细胞Ca2+失衡会导致机械功能障碍、电不稳定（心律失常）和肌肉重塑。钠钙交换体（NCX）是心肌细胞中主要的Ca(2+)处理蛋白之一。目前越来越多的证据表明，NCX1在各种心血管疾病中上调。最近开发的苄氧基苯基NCX抑制剂可有效预防动物模型中的心肌缺血/再灌注损伤和盐敏感性高血压。此外，几项针对基因工程小鼠的实验提供了令人信服的证据，表明这些疾病分别是由心脏和动脉心肌细胞中通过NCX1的病理性Ca2+内流引发的。因此，NCX抑制剂作为治疗心肌再灌注损伤和盐敏感性高血压的新型心血管药物可能具有治疗潜力。然而，NCX抑制剂的疗效以及NCX1在心力衰竭或心律失常中的作用需要更详细的研究。
