Durante W, Schini V B, Catovsky S, Kroll M H, Vanhoutte P M, Schafer A I
Medical Service, Houston Veterans Affairs Medical Center, Texas.
Am J Physiol. 1993 Feb;264(2 Pt 2):H617-24. doi: 10.1152/ajpheart.1993.264.2.H617.
Experiments were performed to examine the effect of the major fibrinolytic protease, plasmin, on the production of nitric oxide from interleukin-1 beta (IL-1 beta)-treated cultured human and rat aortic smooth muscle cells. Incubation of vascular smooth muscle cells with IL-1 beta resulted in significant accumulation of nitrite and nitrate in the culture media. Plasmin, either added exogenously or generated by the reaction of tissue plasminogen activator with plasminogen, potentiated the IL-1 beta-mediated release of nitrite and nitrate from smooth muscle cells in a concentration-dependent manner, without affecting the production of nitrite and nitrate from cells untreated with IL-1 beta. This potentiating effect was abolished when plasmin was incubated with the protease inhibitor, alpha 2-antiplasmin. The perfusates from columns containing IL-1 beta-treated smooth muscle cells relaxed detector blood vessels without endothelium, and the addition of IL-1 beta-treated smooth muscle cells to suspensions of indomethacin-treated platelets inhibited their aggregation. Untreated smooth muscle cells or cells treated with plasmin alone did not have such effects. However, the simultaneous treatment of smooth muscle cells with IL-1 beta and plasmin markedly enhanced both the relaxing activities of the perfusates and the inhibition of platelet aggregation. Treatment of smooth muscle cells with NG-nitro-L-arginine inhibited the cytokine-mediated effects as well as the potentiating effect of plasmin. These results demonstrate that the plasmin can enhance the production of nitric oxide by IL-1 beta-treated vascular smooth muscle cells.
进行实验以研究主要的纤溶蛋白酶——纤溶酶，对经白细胞介素 -1β（IL -1β）处理的培养人及大鼠主动脉平滑肌细胞一氧化氮生成的影响。用IL -1β孵育血管平滑肌细胞导致培养基中亚硝酸盐和硝酸盐显著积累。外源性添加纤溶酶或通过组织纤溶酶原激活剂与纤溶酶原反应生成的纤溶酶，以浓度依赖的方式增强了IL -1β介导的平滑肌细胞中亚硝酸盐和硝酸盐的释放，而不影响未用IL -1β处理的细胞中亚硝酸盐和硝酸盐的生成。当纤溶酶与蛋白酶抑制剂α2 -抗纤溶酶孵育时，这种增强作用被消除。含有经IL -1β处理的平滑肌细胞的柱流出液使无内皮的检测血管舒张，并且将经IL -1β处理的平滑肌细胞添加到经吲哚美辛处理的血小板悬液中可抑制其聚集。未处理的平滑肌细胞或仅用纤溶酶处理的细胞没有这种作用。然而，用IL -1β和平滑肌细胞同时处理显著增强了流出液的舒张活性以及对血小板聚集的抑制作用。用NG -硝基 -L -精氨酸处理平滑肌细胞抑制了细胞因子介导的效应以及纤溶酶的增强作用。这些结果表明，纤溶酶可增强经IL -1β处理的血管平滑肌细胞一氧化氮的生成。
