NO在CCK-8减轻肿瘤坏死因子诱导兔肺动脉反应性变化中的作用

Role of nitric oxide in cholecystokinin-octapeptide alleviation of tumor necrosis factor-alpha induced changes in rabbit pulmonary arterial reactivity

为探讨八肽胆囊收缩素 (CCK 8)缓解内毒素休克时肺动脉高压的作用机制 ,应用离体血管环张力测定技术及一氧化氮合酶 (NOS)检测方法 ,观察了一氧化氮 (NO)在CCK 8减轻肿瘤坏死因子 α (tumornecrosisfactor al pha,TNF α)的抑制肺动脉内皮依赖性舒张反应中的作用。结果显示 :TNF α (4 0 0 0U/ml)孵育 2h时 ,肺动脉对10 -6mol/L苯肾上腺素 (phenylephrine,PE)和 10 -6mol/L乙酰胆碱 (ACh)的收缩反应及内皮依赖性舒张反应均无明显变化。TNF α孵育 7或 14h时 ,肺动脉对 10 -6mol/LACh介导的内皮依赖性舒张反应降低 ,CCK 8(0 5 μg/ml)可逆转TNF α的上述作用。CCK 8本身对正常肺动脉反应性无明显影响。TNF α、CCK 8对PE引起的收缩反应无显著影响。L 精氨酸 (L Arg)可使TNF α 7h组内皮依赖性舒张作用恢复。氨基胍 (AG)不影响各组肺动脉对 10 -6mol/LACh的内皮依赖性舒张反应 ,而使TNF α组肺动脉环对 10 -6mol/LPE的收缩反应显著增加。L 硝基精氨酸(L NNA)使各组肺动脉环对 10 -6mol/LACh反应由舒张变为收缩 ,对 10 -6mol/LPE的收缩反应显著增强。检测 7h各组NOS活性 ,TNF α组、TNF α+CCK 8组均较对照组显著增加 ,CCK 8组与对照组比较无显著差异。上述结果提示 ,CCK 8可逆转TNF α对内皮依赖性舒张?

To explore the mechanism underlying cholecystokinin-octapeptide (CCK-8) induced attenuation in pulmonary arterial hypertension (PAH) in endotoxic shock (ES), the effect of CCK-8 on the changes in rabbit pulmonary arterial reactivity induced by tumor necrosis factor-alpha (TNF-α) was observed with isolated arterial ring technique and by examination of nitric oxide synthase (NOS). The contractile response to 10 -6 mol/L phenylephrine (PE) and the endothelium-dependent relaxation response to 10 -6 mol/L acetylcholine (ACh) were not affected by TNF-α (4*#000 U/ml) after incubation for 2 h; the relaxation response was decreased significantly when the incubation was prolonged to 7 or 14 h, which, however, could be reversed by a concomitant exposure to CCK-8 (0 5 μg/ml), but the incubation of pulmonary arterial rings with CCK-8 (0 5 μg/ml) alone did not bring out any contractile responses. The endothelium-dependent relaxation response to 10 -6 mol/L ACh was restored by L-arginine in the TNF-α group which had been incubated for 7 h, but was not affected by AG in each group, while the contractile response to 10 -6 mol/L PE increased significantly in the TNF-α group. The relaxant response to 10 -6 mol/L ACh changed into a contractile response after preincubation with L-NNA in each group, while the contraction response to 10 -6 mol/L PE increased significantly. The NOS activity increased in the TNF-α and the TNF-α+CCK-8 groups, while no significant difference was observed between the vehicle and the CCK-8 groups. These results suggest that CCK-8 prevents TNF-α induced impairment in endothelium-dependent relaxation response, and the effects of both CCK-8 and TNF-α are related to NO.