大鼠缺氧性肺动脉高压时内皮素和一氧化氮的变化

THE CHANGE IN ENDOTHELIN-1 AND NITRIC OXIDE IN HYPOXIC PULMONARY HYPERTENSION

为探讨缺氧性肺动脉高压 (HPH)时内皮素 1(ET 1)和一氧化氮 (NO)的变化及其关系 ,作者测定了HPH大鼠血浆及肺匀浆中二者的含量 ,用免疫组化检测ET 1、原生型及诱生型一氧化氮合酶 (cNOS、iNOS)在肺内的表达和分布 ,并观察一氧化氮合酶 (NOS)抑制剂亚硝基左旋精氨酸甲酯 (L NAME)对ET 1含量的影响。结果发现 ,HPH组血浆ET 1和NO含量及肺匀浆中NO含量显著高于对照组 (P <0 .0 5 ) ,肺血管内皮、支气管粘膜上皮和血管、支气管平滑肌中ET 1和iNOS的表达明显增强 ,cNOS的表达明显减弱 ,应用L NAME后血浆和肺匀浆中ET 1含量升高 (P <0 .0 5 )。提示正常时NO可能具有抑制ET 1分泌的作用 ,缺氧时增高的ET 1对HPH的形成可能具有一定的意义 。

In order to investigate the change in and relationship between endothelin 1(ET 1) and nitric oxide(NO) in hypoxic pulmonary hypertension(HPH),the content of ET 1 and NO in plasma and lung tissue homogenate, the expression and localization of ET 1, constitutive and inducible nitric oxide synthase(cNOS,iNOS) using immunohistochemistry in HPH of rats were assayed. The effect of NOS inhibitor nitro L arginine methyl ester(L NAME) on the content of ET 1 was also studied. The results showed that the content of ET 1 and NO in plasma of the HPH rats were significantly higher than that of controls; positive expression of ET 1 and iNOS were enhanced in the endothelium of vessels, the epithelium of bronchi and the smooth muscle of vessels and bronchi,but the expression of cNOS weakened The content of ET 1 in plasma and lung tissue homogenate were increased after administration of L NAME. The results indicate that in the normal animals, NO may suppress the secretion of ET 1. The increased ET 1 may play an important role in the development of HPH, and the induced iNOS may be the result of functional adaptation to chronic hypoxia.