Lipoxygenase Products Regulate Nitric Oxide and Inducible Nitric Oxide Synthase Production in Interleukin-1.BETA. Stimulated Vascular Smooth Muscle Cells.
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<B>In cultured vascular smooth muscle cells (VSMCs), interleukin-1β (IL-1β) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. IL-1β also activates phospholipase A<SUB>2</SUB> (PLA<SUB>2</SUB>), and induces lipoxygenase (LOX) and cyclooxygenase-2 (COX-2). The present study investigated whether these metabolites are involved in the regulation of IL-1β-induced NO production and iNOS expression. Pretreatment with ONO-RS-082, the secretory PLA<SUB>2</SUB> (sPLA<SUB>2</SUB>) inhibitor, at 1 to 10μmol/l reduced IL-1β-stimulated nitrite production and iNOS expression. Nordihydroguaiaretic acid (NDGA, 1 to 10μmol/l), the LOX inhibitor, also reduced IL-1β (10 ng/ml)-stimulated nitrite production and iNOS expression in a dose-dependent manner. Exogenous 12(<I>S</I>)-hydroxyeicosatetraenoic acids (HETE) enhanced the IL-1β-stimulated nitrite production and iNOS expression. On the other hand, the COX inhibitors, indomethacin and NS-398, had little effect on nitrite production or iNOS expression. These results suggest that LOX products play important roles in the regulation of stimulus-induced NO production in VSMCs. (<I>Hypertens Res</I> 2003; 26: 177-184)</B>
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日本高血圧学会 | 論文
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