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.
D000636:Aminosalicylic Acids / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors / Q000145:classification / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D019804:Mesalamine; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D019804:Mesalamine