内皮素在N^G-硝基-L-精氨酸甲酯引起的高血压的作用

Role of endothelin in N G-nitric-L-arginine metylester-induced hypertension in rats

目的和方法：在口服ＮＧ－硝基－Ｌ－精氨酸甲酯（ＮＧ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ－ｍｅｔｈｌｅｓｔｅｒ，Ｌ－ＮＡＭＥ）造成的大鼠高血压模型上，观察血浆内皮素（ｅｎｄｏｔｈｅｌｉｎ，ＥＴ）和亚硝酸盐（ＮＯ２）含量，血管内皮素水平和ＮＯ合酶（ＮＯｓｙｎｔｈａｓｅ，ＮＯＳ）活性和ＥＴ受体的变化，以及应用ＥＴ受体阻断剂ＪＫＣ－３０１对高血压的影响。结果：Ｌ－ＮＡＭＥ引起动物血压升高，心肌肥大，血浆ＮＯ生成减少，血管ＮＯＳ活性降低（Ｐ＜００１），血浆和血管ＥＴ含量分别增加８６％和７９％（Ｐ＜００１），血管ＥＴ受体最大结合（Ｂｍａｘ比对照组增加１１３％（Ｐ＜００１）。使用ＪＫＣ－３０１治疗，显著减轻动物的高血压和心肌肥大程度，增加血浆ＮＯ２含量和血管ＮＯＳ活性。

AIM and METHODS: On the model of rat hypertension induced by N G-nitric-L-arginine-metylester(L-NAME),contents of plasma endothelin(ET) and NO 2,changes of aortic ET,NO synthase (NOS)activity and ET receptor binding,and therapeutic effects of ET receptor blocker-JKC-301 were observed. RESULTS:L-NAME resulted in severe hypertension and myocardial hypertrophy and reduced the plasma NO 2 content and aortic NOS activity( P <0 01).The ET contents in plasma and aortic tissue enhanced 86% and 79%,respectively( P <0.01), and the Bmax of ET receptor binding increased 113%( P <0.01).After treatment with JKC-301,hypertension and myocardial hypertrophy were obviously decreased,plasma NO 2 and aortic NOS activity were markedly increased.CONCLUSION:ET mediates the pathogenesis of hypertension induced by inhibiting endothelial derived relaxing factor (EDRF)/NO.