内源性NO在LPS和TNFα诱导离体兔肺动脉反应性变化中的作用

ROLES OF ENDOGENOUS NITRIC OXIDE IN RESPONSIVE CHANGES OF RABBIT PULMONARY ARTERY INDUCED BY LIPOPOLYSACCHARIDE AND TUMOR

目的 :探讨脂多糖 (Lipopolysaccharide ,LPS)和肿瘤坏死因子α(tumornecrosisfactoralpha ,TNFα)所致离体肺动脉反应性张力变化与肺动脉源性一氧化氮 (nitricoxide ,NO)的关系。方法 :离体兔肺动脉环用LPS +TNFα、LPS或溶剂孵育 2h和 6h ,检测肺动脉对乙酰胆碱 (ACh)、硝普钠 (SNP)和苯肾上腺素 (PE)的累积剂量反应 ,以及一氧化氮合酶 (NOS)抑制剂氨基胍 (AG)和Nω 硝基 L 精氨酸 (L NNA) ,NOS底物L 精氨酸 (L Arg)预孵育后肺动脉对PE的收缩反应。结果 :LPS +TNFα孵育 6h后 ,肺动脉对ACh的舒张反应明显低于溶剂组 ,而LPS 2h和LPS +TNFα 2h组该舒张反应无明显变化。LPS +TNFα 2h组对PE的收缩反应呈降低趋势 ,6h时收缩反应明显降低 ,并为AG和L NNA翻转。L Arg可防止AG的抑制效应。LPS 2h和 6h组收缩反应与溶剂组大致相同。与溶剂组相比 ,LPS 2h和 6h、LPS +TNFα 2h组肺动脉对NO供体SNP的舒张反应增强。结论 :LPS

Aim: To explore effect of lipopolysaccharide and tumor necrosis factor alpha (LPS+TNF α) on responsive changes of isolated pulmonary artery and its relation to pulmonary arteryderived nitric oxide(NO). Methods: Pulmonary artery rings (PARs) were incubated with LPS+TNFα. LPS or vehicle at 37℃ for 2 or 6 hours. Then responses of PARs to acetylcholine (ACh), sodium nitroprusside(SNP), and α1adrenoceptor agonist phenylephrine(PE) were measured in cummulative dose manner. In seperate experiment, effect on contraction to PE was observed in above PARs pretreated with aminoguanidine(AG), NωnitroL arginine(LNNA), and Larginine(LArg), respectively. Results: The relaxant. response of PARs to ACh, whose vasodilation is mediated by endotheliumderived NO, in LPS+TNFα 6 h group was signifcantly reduced compared with vehicle, and was little changed in LPS+TNF α 2 h, LPS 2 h and 6 h groups: The contraction to PE had the tendency of decrease in LPS+ TNFα 2h group and was significantly reduced in LPS+ TNFα 6h group, the latter was reversed by pretreatment of AG and LNNA. L Arg could prevent the effect of AG. Contraction of LPS 2h and 6h groups was similar to vehicle group. Relaxation of PARs to SNP increased in LPS 2h and 6h, LPS+TNF α 2h groups compared with vehicle group.Conclusion: LPS+TNF α could regulate responses of pulmonary artery by influence of NO production in the artery itself.