内源性CO/NO在内毒素休克大鼠主动脉低收缩反应中的介导作用

Roles of endogenous carbon monoxide/nitric oxide on vascular hyporeactivity in thoracic aorty of endotoxin shock rats

目的 :探讨血红素 HO CO cGMP和L 精氨酸 NOS NO cGMP通路对内毒素休克 (ES)大鼠主动脉血管张力的影响。方法 :SD大鼠 12只 ,分为LPS组和对照组。用离体血管环张力测定技术 ,观察胸主动脉环 (TARs)对苯肾上腺素 (PE)累积收缩反应 ,并分别用正铁血红素 (He)、L 精氨酸 (L Arg)、锌原卟啉 (ZnPP IX)、氨基胍 (AG)、N 硝基 L 精氨酸 (L NNA)或亚甲蓝 (MB)与TARs共同孵育 2 0min后 ,比较两组对PE的收缩反应、动脉组织中CO/NO的含量、HO 1和NOS活性。结果 :LPS组主动脉对PE累积收缩反应明显降低 ,用ZnPP IX或AG孵育后 ,可部分逆转低血管反应性 ;经L NNA或MB孵育 ,可完全逆转低血管反应 ;而用He或L Arg孵育可不同程度加重低血管反应状态。LPS组动脉组织中CO/NO的含量明显上升 ,HO 1/NOS活性显著增加。结论 :LPS可激活HO 1和iNOS ,大量增加CO /NO合成 ,cGMP水平上升 ,共同介导ES大鼠主动脉低收缩反应。

Objective:To explore the effects of heme heme oxygenase(HO) carbon monoxide(CO) cyclic GMP(cGMP)and L Arginine nitric oxide synthase(NOS) nitric oxide(NO) cGMP on aortic vascular hyporeactivity in endotoxin shock (ES)rats. Using isolated vascular ring tension detecting technique,cummulative responses of thoracic aortic rings(TARs)to phenylephrine(PE)were measured. Effects on contractive responses to PE were observed in TARs incubated with hemin(He)?L arginine(L Arg),zinc protoporphyrin IX(ZnPP IX),aminoguanidine(AG),N( nitro L arginine(L NNA )or methylene blue(MB),respectively. The content of CO / NO and the activity of HO 1/ NOS were measured. Results:The cummulative dose contractive responses to PE were depressed by pretreated with LPS. In LPS group,the vascular hyporeactivity was partly reversed by incubation with ZnPP IX or AG and restored to normal by incubation with L NNA or MB. Incubation of TARs with He or L Arg showed to make the vascular hyporeactivity worse in different degree. Both the contents of CO / NO and the activity of HO 1/ NOS were significiantly increased in aortic tissue of ES rats. Conclusion:The result revealed that LPS could activate HO 1 and iNOS,instead it reduced CO/NO production,then decrease the content of cGMP,lead to the hyporesponsiveness in ES rats.