Nitric oxide synthase as a novel target and cytoprotective mediator of aspirin in vascular endothelial cells

The present study investigates the involvement of nitric oxide (NO) in antioxidant cellular protection induced by aspirin. A 12-hour preincubation with aspirin protected endothelial cells from hydrogen peroxide-mediated toxicity, whereas other nonsteroidal anti-inflammatory drugs failed to exert a cytoprotective action. Aspirin-induced endothelial protection was abrogated in the presence of the NO scavenger PTIO and the inhibitor of soluble guanylyl cyclase, ODQ. Moreover, the L-arginine antagonist L-NMMA led to complete inhibition of aspirin-dependent cytoprotection. Correspondingly, aspirin enhanced NO synthase activity and intracellular cyclic GMP accumulation in endothelial cells. Protein expression of endothelial NO synthase remained unaffected in the presence of aspirin. Our data suggest that endothelial NO synthase is a site of action of aspirin and that the NO/cyclic GMP system assumes a crucial function in mediating the cytoprotective action of aspirin.