内皮舒张因子在缺氧肺动脉收缩中的作用

Actions of Endothelium Derived Relaxing Factor on Hypoxic Pulmonary Vasoconstriction

本工作在离体灌流肺动脉环模型及培养的牛肺动脉内皮细胞探讨内皮舒张因子 (EDRF/NO)在缺氧肺动脉收缩中的作用。结果发现 ,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 -2 mol/L)分别升高 (+ 80 % ,P <0 .0 1)和降低 (-35 % ,P <0 .0 5 )缺氧肺动脉收缩幅度 ;给予硝酸甘油 (10 -4 mol/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 ;用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。结果提示缺氧时NOS基因表达受抑及NO合成释放降低可能是缺氧肺动脉收缩的发生机制之一。

We studied the actions of endothelium derived relaxing factor (EDRF) on hypoxic pulmonary vasoconstriction(HPV) of isolated perfused pulmonary artery ring.The results showed that HPV was increased 80%(P< 0.01 ) by 10 -4 mol/L L NNA (an NO synthesis inhibitor ) or decreased 35% (P<0.05) by 10 -2 mol/L L Arg (a precursor of NO).Supplement of EDRF/NO,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.Northern blot showed that hypoxia suppressed mRNA expression of nitric oxide synthase(NOS) in cultured endothelial cells from bovine pulmonary artery.The results suggest that decrease of NOS mRNA expression and,in turn,decrease of NO synthesis/release may be related to HPV pathogenesis.