Plasmin potentiates induction of nitric oxide synthesis by interleukin- 1β in vascular smooth muscle cells

Abstract

Experiments were performed to examine the effect of the major fibrinolytic protease, plasmin, on the production of nitric oxide from interleukin-1β (IL-1β)-treated cultured human and rat aortic smooth muscle cells. Incubation of vascular smooth muscle cells with IL-1β 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-1β-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-1β. This potentiating effect was abolished when plasmin was incubated with the protease inhibitor, α2-antiplasmin. The perfusates from columns containing IL-1β-treated smooth muscle cells relaxed detector blood vessels without endothelium, and the addition of IL-1β- 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-1β and plasmin markedly enhanced both the relaxing activities of the perfusates and the inhibition of platelet aggregation. Treatment of smooth muscle cells with N(G)-nitro-L-arginine inhibited the cytokine-mediated effects as well as the potentiating effect of plasmin. These results demonstrate that plasmin can enhance the production of nitric oxide by IL-1β-treated vascular smooth muscle cells.