过氧亚硝基阴离子对离体兔肺动脉反应性变化的影响

Effect of peroxynitrite on the reactivity of rabbit pulmonary arteries in vitro

探讨过氧亚硝基阴离子(peroxynitrite,ONOO^-)对离体兔肺动脉反应性变化的影响。用离体血管环技术观察ONOO^-孵育后肺动脉对钙离子载体A23187、ADP、ACh、硝普钠(sodium nitroprusside,SNP)和苯肾上腺素(phenylephrine,PE)的反应性张力变化。结果显示:(1)ONOO^-孵育后肺动脉对A23187、ADP和ACh引起的舒张反应明显降低,ONOO^-抑制内皮依赖受体依赖或受体非依赖性舒张反应有量效关系;(2)ONOO^-孵育可剂量依赖性抑制肺动脉对SNP的舒张反应;(3)0.5 mmol/L ONOO^-孵育后肺动脉对PE的收缩反应明显增强,而1.0和2.0mmol/L ONOO^-导致肺动脉的收缩反应明显降低;(4)溶剂对肺动脉的反应性无明显影响,dec ONOO^-对PE和ADP的反应性影响不大,但可增强A23187、ACh和SNP的舒张反应。结果表明,ONOO^-可改变离体肺动脉的反应性。

To investigate the effect of peroxynitrite (ONOO^-) on the reactivity of rabbit pulmonary artery,the responses of rabbit pulmonary artery tings (PARs) pre-incubated with ONOO^- to endothelium-dependent and receptor-dependent relaxants ACh and ADP, endothelium-dependent and receptor-independent relaxant calcium ionophore A23187, endothelium-independent relaxant sodium nitroprusside (SNP) and α1-adrenoceptor agonist phenylephrine (PE) were observed in vitro in an accumulative manner. (1) Relaxations of PARs to ACh, calcium ionophore A23187 and ADP were markedly impaired with shift of accumulative doseresponse curve of each agonist to the tight. Inhibition of endothelium-dependent and receptor-dependent or independent relaxation by ONOO^- was dose-dependent. (2)ONOO^- incubation inhibited SNP-induced relaxation in a dose-dependent manner. (3) Contractile response of PARs to PE varied with the different doses of ONOO^-. In PARs pre-incubated with 0.5 mmol/L ONOO^-, contractile response was significantly enhanced with shift of PE accumulative dose-response curve to the left, whereas in PARs pre-incubated with 1.0 mmol/L or 2.0 mmol/L ONOO^-, it was markedly reduced with right shift of PE accumulative dose-response curve.(4) Vehicle of ONOO^- had no effect on responses to each agonist. Decomposed ONOO^- had minimal effect on the response to PE and ADP, in contrast, relaxation of PARs to ACh, A23187 and SNP were enhanced. These results indicate that ONOO^- may contribute to regulatory disorder of pulmonary artery reactivity.