Nitroaspirins and Morpholinosydnonimine but Not Aspirin Inhibit the Formation of Superoxide and the Expression of gp91 phox Induced by Endotoxin and Cytokines in Pig Pulmonary Artery Vascular Smooth Muscle Cells and Endothelial Cells

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Abstract
Background— Although nonsteroidal antiinflammatory drugs (NSAIDs) are ineffective in treating acute respiratory distress syndrome (ARDS), inhalational NO has proved to be useful. NO-donating NSAIDs may therefore be more effective in treating ARDS than NSAIDs alone. Because oxidant stress is central to the pathophysiology of ARDS, the effect of nitroaspirins (NCX 4016, NCX 4040, and NCX 4050) compared with morpholinosydnonimine (SIN-1; an NO donor) and aspirin (ASA) on superoxide (O2·−) formation and gp91phox (an active catalytic subunit of NADPH oxidase) expression in pig pulmonary artery vascular smooth muscle cells (PAVSMCs) and endothelial cells (PAECs) was investigated. Methods and Results— Cultured PAVSMCs and PAECs were incubated with lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, and interleukin (IL)-1α (with or without NO-ASA, SIN-1, or ASA) for 16 hours, and O2·− release was measured by use of the reduction of ferricytochrome c. The expression of gp91phox was assessed by use of Western ...