Catalytic consumption of nitric oxide by 12/15- lipoxygenase: Inhibition of monocyte soluble guanylate cyclase activation

12/15-Lipoxygenase (LOX) activity is elevated in vascular diseases associated with impaired nitric oxide ((⋅)NO) bioactivity, such as hypertension and atherosclerosis. In this study, primary porcine monocytes expressing 12/15-LOX, rat A10 smooth muscle cells transfected with murine 12/15-LOX, and purified porcine 12/15-LOX all consumed (⋅)NO in the presence of lipid substrate. Suppression of LOX diene conjugation by (⋅)NO was also found, although the lipid product profile was unchanged. (⋅)NO consumption by porcine monocytes was inhibited by the LOX inhibitor, eicosatetraynoic acid. Rates of arachidonate (AA)- or linoleate (LA)-dependent (⋅)NO depletion by porcine monocytes (2.68 ± 0.03 nmol ⋅ min(−1) ⋅ 10(6) cells(−1) and 1.5 ± 0.25 nmol ⋅ min(−1) ⋅ 10(6) cells(−1), respectively) were several-fold greater than rates of (⋅)NO generation by cytokine-activated macrophages (0.1–0.2 nmol ⋅ min(−1) ⋅ 10(6) cells(−1)) and LA-dependent (⋅)NO consumption by primary porcine monocytes inhibited (⋅)NO activation of soluble guanylate cyclase. These data indicate that catalytic (⋅)NO consumption by 12/15-LOX modulates monocyte (⋅)NO signaling and suggest that LOXs may contribute to vascular dysfunction not only by the bioactivity of their lipid products, but also by serving as catalytic sinks for (⋅)NO in the vasculature.