A study on the mechanism of accelerated vascular injury induced by sodium loading

众所周知，过量摄入钠是心血管疾病的一个危险因素，因为它会使血压升高。然而，据报道，钠负荷促进心血管疾病独立于其对血压的影响。方法与结果采用大鼠股动脉丝损伤模型，观察钙调磷酸酶在钠负荷性血管炎症中的作用。Wistar Kyoto（WKY）和Dahl耐盐（DR）等钠负荷正常大鼠主动脉钙调磷酸酶活性明显高于对照组（WKY和DR）。与对照组WKY和DR大鼠相比，钠负荷的WKY和DR大鼠的内膜形成也显著增强。表达钙调磷酸酶显性阴性突变体（AdCalAΔC92Q）的腺病毒的基因转移显著抑制了钠负荷的WKY和DR大鼠的新内膜形成，其水平与对照WKY和DR大鼠相似。高血压大鼠（如自发性高血压大鼠和高钠盐敏感大鼠）钙调磷酸酶活性和新内膜形成增强更为显著；AdCalAΔC92Q感染显著抑制了这些大鼠的内膜形成。结论钠负荷可促进正常和高血压大鼠血管炎症，钙调磷酸酶在这一过程中起关键作用。

Background It is well known that an excessive intake of sodium is a risk factor for cardiovascular disease because it raises the blood pressure. However, sodium loading reportedly promotes cardiovascular disease independently of its effect on blood pressure. Methods and Results We examined the role of calcineurin in sodium loading-induced vascular inflammation using a wire injury model of the rat femoral artery. Calcineurin activity in the aorta was significantly higher in sodium-loaded normotensive rats such as Wistar Kyoto(WKY) and Dahl salt-resistant(DR) rats than that in control WKY and DR rats. Neointimal formation was also significantly enhanced in sodium-loaded WKY and DR rats as compared with control WKY and DR rats. Gene transfer of an adenovirus expressing a dominant-negative mutant of calcineurin(AdCalAΔC92Q) significantly suppressed neointimal formation in sodium-loaded WKY and DR rats to a level similar to that observed in control WKY and DR rats. Calcineurin activity and neointimal formation were more significantly enhanced in hypertensive rats, such as spontaneously hypertensive rats and sodium-loaded Dahi salt-sensitive rats ; AdCalAΔC92Q infection significantly suppressed neointimal formation in these rats. Conclusions These results suggest that sodium loading promotes vascular inflammation in normotensive and hypertensive rats and that calcineurin plays a pivotal role in this process.