内皮素在大鼠高血压心肌肥大中的作用

Role of Endothelin in Hypertensive Myocardial Hypertrophy of Rats

目的研究内皮素（ＥＴ）在一氧化氮合酶（ＮＯＳ）抑制剂亚硝基左旋精氨酸甲酯（Ｌ－ＮＡＭＥ）诱导的高血压心肌肥大中的作用及ＥＴＡ受体阻断剂ＪＫＣ－３０１的保护效应。方法复制大鼠Ｌ－ＮＡＭＥ高血压模型，动物分对照组、高血压组和ＪＫＣ－３０１治疗组，测定心重、血浆及心肌ＥＴ水平和心肌丝裂素活化蛋白激酶（ＭＡＰＫ）活性。结果高血压动物的心重、ＥＴ水平和心肌ＭＡＰＫ活性较对照组都显著升高（Ｐ＜０．０１或０．０５），加用ＪＫＣ－３０１治疗则较高血压组ＥＴ水平不变，但血压、心重和ＭＡＰＫ活性均降低（Ｐ＜０．０１或０．０５），心肌ＭＡＰＫ活性与左心室肥大程度呈正相关（ｒ＝０．８２，Ｐ＜０．０１）。结论一氧化氮缺乏的心肌肥大可能是由ＥＴ所介导的。

Aim To investigate the role of endothelin(ET) in the nitric oxide synthase(NOS) inhibitor, NG nitro L arginine metyl ester(L NAME), induced cardiac hypertrophy of rats and the protective effect of JKC 301, the endothelin receptor A antagonist.\ Methods The cardiac weight,ET levels of plasma and cardiac tissue, cardiac mitogen activated protein kinase(MAPK) activity were measured in three groups of rats:control,hypertension induced by L NAME,and hypertension treated with JKC 301 group.\ Results Cardiac weight,ET levels and MAPK activity were elevated significantly in hypertensive rats( P <0.01 or 0.05, vs control).\ JKC 301 decreased blood pressure, cardiac weight and MAPK activity(P<0.01 or 0.05, vs hypertensive rats).\ There was a positive correlation between cardiac MAPK activity and left ventricular hypertrophy( r=0.82,P <0.01).\ Conclusion Myocardial hypertrophy deficiency of nitric oxide(NO) is likely to be mediated by ET which can be prevented by ET receptor antagonist.