Docosahexaenoic acid potentiates interleukin-1β induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells

摘要

class="enumerated" style="list-style-type:decimal">The effect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and inducible NO synthase (iNOS) expression induced by interleukin (IL)-1β, and whether the effect of DHA is related to its effect on mitogen-activated protein kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle cells (VSMCs).DHA and eicosapentaenoic acid (EPA), although less potent, increased the NO production induced by IL-1β (3 ng ml⁻¹) in a concentration-dependent manner (3–30 μM) Arachidonic acid had no significant effect. The stimulatory effect of DHA (30 μM) on the NO production was more obvious at lower concentrations of IL-1β.IL-1β induced iNOS protein and mRNA expressions, which were significantly potentiated by DHA. EPA (30 μM) had a tendency to increase the iNOS protein and mRNA expressions, but arachidonic acid had no effect.IL-1β-induced iNOS protein expression was significantly inhibited by PD 98059 (10 μM), a selective inhibitor of p44/42 MAPK kinase, both in the absence and the presence of DHA. SB 203580 (10 μM), a selective inhibitor of p38 MAPK activity, had no significant effect, although had a tendency to inhibit slightly.IL-1β increased the phosphorylation of p44/42 MAPK, while it did not apparently increase the phosphorylation of p38 MAPK. DHA significantly potentiated the IL-1β-induced phosphorylation of p44/42 MAPK, while it had no significant effect on the phosphorylation of p38 MAPK.These results suggest that DHA increases NO production by potentiating iNOS expression induced by IL-1β through mechanism involving p44/42 MAPK signalling cascade in rat VSMCs. The present study may contribute to the understanding of basic mechanisms underlying the beneficial effects of DHA on various cardiovascular disorders.