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 microM) in a concentration-dependent manner. Removal of endothelium, inhibition of guanylate cyclase by methylene blue, inhibition of NO biosynthesis by NG-nitro-L-arginine as well as in inactivation of NO by oxyhemoglobin abolished the effect of 5-aminosalicylic acid. The antiaggregatory effects of 3-morpholinosydnonimine and rat peritoneal neutrophils, which are due to release of NO, were diminished in a concentration-dependent manner by 5-aminosalicylic acid (50-250 microM). In both experimental models the effects of 5-aminosalicylic acid were significantly reduced by superoxide dismutase in a concentration which alone exhibited no effect. Since NO might act as a cytotoxic and vasodilating mediator, our results suggest that inactivation of NO by 5-aminosalicylic acid could contribute to the therapeutic activity of the drug in inflammatory bowel disease.