Effect of 5-aminosalicylic acid and 4-aminosalicylic acid on precontracted rat aortic strips and on NO-mediated inhibition of platelet aggregation

Abstract

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. Phennylephrine-precontracted rat aortic strips with intact endothelium were further contracted by 5-ASA (50–200 μmol/1) and 4-ASA (1–20 mmol/1) in a concentration-dependent manner. Removal of endothelium, inhibition of guanylate cyclase by methylene blue, inhibition of NO biosynthesis byN ^G-nitro-l-arginine as well as inactivation of NO by oxyhemoglobin abolished the effects of 5-ASA and 4-ASA. The antiaggregatory effects of 3-morpholinosydnonimine (SIN-1) and rat peritoneal neutrophils (RPN) were diminished in a concentration-dependent manner by 5-ASA (50–250 μmol/l), but not by 4-ASA (up to 20 mmol/l). In the presence of superoxide dismutase (SOD), 5-ASA did not antagonize NO-mediated effects on platelets. 5-ASA up to 100 μmol/l did not affect NO synthase from rat brain, while a concentration of 1 mM caused 21% inhibition. Since NO might act as a cytotoxic mediator, our results suggest that inactivation of NO by 5-ASA and higher concentrations of 4-ASA could contribute to the therapeutic activity of the drugs in inflammatory bowel disease (IBD).