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

12/15-lipoxygenase (LOX) activity is elevated in vascular diseases associat ed with impaired nitric oxide ((NO)-N-.) 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 subst rate. Suppression of LOX diene conjugation by (NO)-N-. was also found, alth ough the lipid product profile was unchanged:NO consumption by porcine mono cytes was inhibited by the LOX inhibitor, eicosatetraynoic acid. Rates of a rachidonate (AA)- or linoleate (LA)-dependent (NO)-N-. 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'tdO generation by cytokine-activated macrophages (0.1-0.2 nmol . min(-1). 10(6) cells(-1)) and LA-dependent (NO)-N-. consumption by primary porcine monocytes inhibited (NO)-N-. activation of soluble guanylate cyclas e. These data indicate that catalytic (NO)-N-. consumption by 12/15-LOX mod ulates monocyte (NO)-N-. signaling and suggest that LOXs may contribute to vascular dysfunction not only by the bioactivity of their lipid products, b ut also by serving as catalytic sinks for (NO)-N-. in the vasculature.