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)-mo nomethyl-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-dep endent contraction. Addition of L-NAME (30-300 muM) or L-NMMA (30-300 muM) to the Tyrode's solution increased in a concentration-dependent f ashion the amplitude of the ricinoleic acid-evoked responses. L-Argini ne (900 muM), a natural substrate of NO synthase, but not D-arginine ( 900 muM), counteracted the effect of L-NAME (300 muM). The potentiatin g effect of L-NAME was also prevented by sodium nitroprusside (0.1-1 m uM), a generator of NO. These results provide evidence that endogenous NO may modulate the contraction of rat ileum induced by ricinoleic ac id. As the contraction induced by ricinoleic acid is not blocked by te trodotoxin (0.6 and 6.0 muM) the contractile effect of ricinoleic acid results mainly from a direct action on the smooth muscle.