EFFECT OF 5-AMINOSALICYLIC ACID AND 4-AMINOSALICYLIC ACID ON PRECONTRACTED RAT AORTIC STRIPS AND ON NO-MEDIATED INHIBITION OF PLATELET-AGGREGATION

We have examined the interactions of 5-aminosalicylic acid (5-ASA) and 4-aminosalicylic acid (4-ASA) with nitric oxide (NO) on rat aorta and human platelets. Phenylephrine-precontracted rat aortic strips with i ntact endothelium were further contracted by 5-ASA (50-200 mu mol/l) a nd 4-ASA (1-20 mmol/l) in a concentration-dependent manner. Removal of endothelium, inhibition of guanylate cyclase by methylene blue, inhib ition of NO biosynthesis by N-G-nitro-L-arginine as well as inactivati on of NO by oxyhemoglobin abolished the effects of 5-ASA and 4-ASA. Th e antiaggregatory effects of 3-morpholinosydnonimine (SIN-1) and rat p eritoneal neutrophils (RPN) were diminished in a concentration-depende nt manner by 5-ASA (50-250 mu mol/l), but not by 4-ASA (up to 20 mmol/ l). In the presence of superoxide dismutase (SOD), 5-ASA did not antag onize NO-mediated effects on platelets. 5-ASA up to 100 mu mol/l did n ot affect NO synthase from rat brain, while a concentration of 1 mM ca used 21% inhibition. Since NO might act as a cytotoxic mediator, our r esults suggest that inactivation of NO by 5-ASA and higher concentrati ons of 4-ASA could contribute to the therapeutic activity of the drugs in inflammatory bowel disease (IBD).