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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1345.)
© 2003 American Heart Association, Inc.

Vascular Biology

Aspirin Protects Endothelial Cells From Oxidant Damage Via the Nitric Oxide-cGMP Pathway

Nina Grosser; Henning Schröder

From the Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle, Germany.

Correspondence to Dr Henning Schröder, School of Pharmacy, Martin Luther University, Wolfgang-Langenbeck-Str. 4, 06099 Halle (Saale), Germany. E-mail schroeder{at}pharmazie.uni-halle.de

Objectives— Aspirin is known to exert cytoprotection by presently unidentified mechanisms. This study investigates the involvement of nitric oxide (NO) in antioxidant cellular protection induced by aspirin.

Methods and Results— A 24-hour incubation with hydrogen peroxide markedly reduced viability of cultured endothelial cells. Preincubation with aspirin (3 to 30 µmol/L) protected endothelial cells from hydrogen peroxide–mediated toxicity and increased viability in a concentration-dependent fashion by up to 95% of control. This effect was specific in that other nonsteroidal anti-inflammatory drugs, such as salicylate or indomethacin, did not alter hydrogen peroxide toxicity. Aspirin-induced endothelial protection was abrogated in the presence of the NO scavenger PTIO (30 µmol/L) and the inhibitor of soluble guanylyl cyclase ODQ (1 µmol/L). Moreover, the L-arginine antagonist L-NMMA (25 µmol/L), but not its D-enantiomer, led to complete inhibition of aspirin-dependent cytoprotection. Correspondingly, aspirin enhanced NO synthase activity (citrulline formation) and intracellular cyclic GMP accumulation in endothelial cells. Protein expression of endothelial NO synthase remained unaffected in the presence of aspirin.

Conclusions— 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.

Key Words: aspirin • nitric oxide • cyclic GMP • endothelium • antioxidant defense mechanism

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