EICOSAPENTAENOIC ACID POTENTIATES THE PRODUCTION OF NITRIC-OXIDE EVOKED BY INTERLEUKIN-1-BETA IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS

Experiments were designed to determine whether the omega3-unsaturated fatty acid eicosapentaenoic acid affects the production of nitric oxid e evoked by interleukin-1beta in cultured vascular smooth muscle cells . Incubation of cultured rat or human aortic smooth muscle cells with interleukin-1beta evoked a time- and concentration-dependent release o f nitrite, an oxidation product of nitric oxide. The exposure of cells to interleukin-1beta in combination with eicosapentaenoic acid caused a significantly larger production of nitrite than that evoked by the cytokine alone. The potentiation by eicosapentaenoic acid was concentr ation-dependent. The production of nitrite evoked by equieffective con centrations of interleukin-1beta in the presence and absence of eicosa pentaenoic acid were inhibited to a similar extent by nitro L-arginine (an inhibitor of nitric oxide synthase), transforming growth factor b eta1, platelet-derived growth factor(AB) and thrombin. The addition of interleukin-1beta-activated smooth muscle cells to suspensions of was hed and indomethacin-treated platelets inhibited the aggregation cause d by thrombin. The inhibitory effect was enhanced when the smooth musc le cells were exposed to the cytokine in the presence of eicosapentaen oic acid prior to the experiment. Smooth muscle cells exposed to inter leukin-1beta and eicosapentaenoic acid did not affect platelet aggrega tion in the presence of oxyhemoglobin or methylene blue. Untreated cel ls or cells exposed to the fatty acid alone did not have such effects. These observations suggest that eicosapentaenoic acid potentiates the production of nitric oxide evoked by interleukin-1beta in vascular sm ooth muscle.