INTERACTION OF 5-AMINOSALICYLIC ACID WITH NITRIC-OXIDE ON RAT AORTIC STRIPS AND HUMAN PLATELETS

We have examined the interactions of 5-aminosalicylic acid with nitric oxide (NO). Phenylephrine-precontracted rat aortic strips with intact endothelium were further contracted by 5-aminosalicylic acid (50-200 mu M) in a concentration-dependent manner. Removal of endothelium, inh ibition of guanylate cyclase by methylene blue, inhibition of NO biosy nthesis by N-G-nitro-L-arginine as well as inactivation of NO by oxyhe moglobin abolished the effect of 5-aminosalicylic acid. The antiaggreg atory effects of 3-morpholinosydnomimine and rat peritoneal neutrophil s, which are due to release of NO, were diminished in a concentration- dependent manner by 5-aminosalicylic acid (50-250 mu M). In both exper imental models the effects of 5-aminosalicylic acid were significantly reduced by superoxide dismutase in a concentration which alone exhibi ted no effect. Since NO might act as a cytotoxic and vasodilating medi ator, our results suggest that inactivation of NO by 5-aminosalicylic acid could contribute to the therapeutic activity of the drug in infla mmatory bowel disease.