INHIBITORS OF NITRIC-OXIDE SYNTHASE ENHANCE RAT ILEUM CONTRACTIONS INDUCED BY RICINOLEIC ACID IN-VITRO

The effects of N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA), inhibitors of nitric oxide (NO) synthase, were studied on ricinoleic acid-evoked contractions in rat isolated ileum. Ricinoleic acid (10(-5) to 10(-4) M) caused a concentration-dependent contraction. Addition of L-NAME (30-300 muM) or L-NMMA (30-300 muM) to the Tyrode's solution increased in a concentration-dependent fashion the amplitude of the ricinoleic acid-evoked responses. L-Arginine (900 muM), a natural substrate of NO synthase, but not D-arginine (900 muM), counteracted the effect of L-NAME (300 muM). The potentiating effect of L-NAME was also prevented by sodium nitroprusside (0.1-1 muM), a generator of NO. These results provide evidence that endogenous NO may modulate the contraction of rat ileum induced by ricinoleic acid. As the contraction induced by ricinoleic acid is not blocked by tetrodotoxin (0.6 and 6.0 muM) the contractile effect of ricinoleic acid results mainly from a direct action on the smooth muscle.