NO样舒张因子和内皮素在急性缺氧肺动脉高压中的作用

在大鼠急性缺氧肺动脉高压模型、离体灌流肺动脉环模型及培养的牛肺动脉内皮细胞探讨ＮＯ样舒张因子（ＮＯ－ＬＲＦ）和内皮素（ＥＴ）在急性缺氧肺动脉高压中的作用。结果发现：ＮＯ合成前体Ｌ－Ａｒｇ（２５０ｍｇ／ｋｇ，ｉｖ）可有效降低急性缺氧肺动脉高压的幅度；在内皮完整血管环加入ＮＯ合成抑制剂Ｌ－ＮＮＡ（１０－４ｍｏｌ／Ｌ）、ＮＯ合成前体Ｌ－Ａｒｇ（１０－２ｍｏｌ／Ｌ）分别升高（＋８０％，Ｐ＜０．０１）和降低（－３５％，Ｐ＜０．０５）缺氧肺动脉收缩幅度，给予硝酸甘油（１０－４ｍｏｌ／Ｌ）直接补充ＮＯ可降低缺氧肺动脉收缩幅度；此效应可被可溶性鸟苷酸环化酶抑制剂亚甲蓝部分逆转；内皮素抗血清或内皮素Ａ受体结抗剂ＢＱ１２３对急性缺氧肺动脉高压及缺氧肺动脉收缩没有明显影响；Ｎｏｒｔｈｅｒｎ印渍杂交技术显示缺氧使培养的牛肺动脉内皮细胞ＮＯ合成酶（ＮＯＳ）基因表达明显受抑乃至缺失．结果提示：缺氧时ＮＯＳ基因表达受抑及ＮＯ－ＬＲＦ合成释放降低可能是急性缺氧肺动脉高压的发生机制之一，内皮素不起主要作用．

Effects of No-like Relaxing Factor and Endothelin on Acute Hypoxic Pulmonary Hypertension

In this paper,we studied the effects of nitric oxide-like relaxing factor (NO-LRF)and endothelin on acute hypoxic pulmonary hypertension(AFWH)with acute hypoxic pulmonary hypertension animal model,isolated perfused pulmonary artery and cultured endothelial cells from bovine pulmonary artery. The results showed that AHPHwas decresed by L-Arg(a precursor of NO-LRF, 250mg/kg,iv)and that bypoxic pulmonary vasoconstriction (HPV) was increased 80% (P<0. 01 )by 10e-4 mol/L L-NNA (an NO-LRF synthesis inhibitor)or decreased 35% (P<0. 05)by 10e-2 mol/L L-Arg.Supplyment of No-LRF, by addition of nitroglycerine to pulmonary artery rings,lowered HPV by 71 % (P<0. 01)and this effect was partially blocked by methylene blue,guanylic acid cyclase inhibitor. Endothelin antibody and BQ123(ET A receptor antagonist)was nosignificant effects on AHPH and HPV. Northern blot showed that hypoxia suppressed mRNA expression of nitric oxide synthase (NOS) in cultured endothelial cells from bovine pulmonary. Above results suggest that decrease of NOS gene expression and,in turn,decrease of NO synthesis/release may be related to AHPH pathogensis.