1 The e ect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and inducible NO synthase (iNOS) expression induced by interleukin (IL)-1b, and whether the e ect of DHA is related to its e ect on mitogen-activated protein kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle cells (VSMCs). 2 DHA and eicosapentaenoic acid (EPA), although less potent, increased the NO production induced by IL-1b (3 ng ml 71 ) in a concentration-dependent manner (3 ± 30 mM) Arachidonic acid had no signi®cant e ect. The stimulatory e ect of DHA (30 mM) on the NO production was more obvious at lower concentrations of IL-1b. 3 IL-1b induced iNOS protein and mRNA expressions, which were signi®cantly potentiated by DHA. EPA (30 mM) had a tendency to increase the iNOS protein and mRNA expressions, but arachidonic acid had no e ect. 4 IL-1b-induced iNOS protein expression was signi®cantly inhibited by PD 98059 (10 mM), a selective inhibitor of p44/42 MAPK kinase, both in the absence and the presence of DHA. SB 203580 (10 mM), a selective inhibitor of p38 MAPK activity, had no signi®cant e ect, although had a tendency to inhibit slightly. 5 IL-1b increased the phosphorylation of p44/42 MAPK, while it did not apparently increase the phosphorylation of p38 MAPK. DHA signi®cantly potentiated the IL-1b-induced phosphorylation of p44/42 MAPK, while it had no signi®cant e ect on the phosphorylation of p38 MAPK. 6 These results suggest that DHA increases NO production by potentiating iNOS expression induced by IL-1b through mechanism involving p44/42 MAPK signalling cascade in rat VSMCs. The present study may contribute to the understanding of basic mechanisms underlying the bene®cial e ects of DHA on various cardiovascular disorders.

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