Superoxide dismutase mimetic M40403 improves endothelial function in apolipoprotein(E)-deficient mice

Abstract

1. Overproduction of superoxide anions in the vascular wall contributes to endothelial dysfunction in vascular disease. A superoxide-generating reduced β-nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has recently been identified as a major source of oxidative radicals in vascular tissues. We studied the effects of a synthetic manganese-containing superoxide dismutase (SOD) mimetic, M40403, on NADPH oxidase-dependent superoxide generation and on endothelial dysfunction. 2. In rat aortic smooth muscle cells, NADPH (I00 μM) markedly stimulated superoxide production as detected by lucigenin (5 μM)-enhanced chemiluminescence. M40403 reduced NADPH oxidase-dependent superoxide product..