Nitric oxide (NO) has been shown to mediate nonadrenergic-noncholinergic relaxation in gastrointestinal (GI) smooth muscle cells. As GI smooth muscles relaxations are partly dependent on NO, we decided to investigate the effect of sodium nitroprusside (SNP) on the longitudinal muscle contraction of the isolated guinea pig ileum. Increasing concentrations of SNP (10(-10)M, 10(-9)M, 10(-8)M, 10(-7)M, 10(-6)M and 10(-5)M) reduced ileum contractions stimulated by electrical stimulation (ES) (8-76%; p LT 0.05) and by acetylcholine (Ach) (23-62%; p LT 0.05) significantly and in a concentration-dependent manner. Furthermore, treatment with an inhibitor of the soluble guanylate cyclase, methylene blue (10 mM), antagonized significantly the relaxing effect of SNP (0-39%; p LT 0.05, p LT 0.01, p LT 0.001 for ES- and 4-27%; p LT 0.05 for Ach-induced contractions). The results show that treatment with 1 mu M manganese-containing superoxide dismutase (MnSOD) and 10 mu M L-arginine (L-arg) caused a significant decrease in SNP induced relaxations (6-55%; p LT 0.05, p LT 0.001 and 2-46%; p LT 0.05, p LT 0.01 for ES- and 15-28%; p LT 0.05, p LT 0.01, p LT 0.001 and 12-32%; p LT 0.05, p LT 0.01 for Ach-induced contractions, respectively). In conclusion, our data suggest that SNP, which releases NO, is able to depress longitudinal muscle contraction of the isolated guinea pig ileum, suggesting that exogenous application of NO inhibits intestinal contractions of smooth muscle cells and that cGMP mediates the response to NO. In addition, MnSOD and L-arg decreased the relaxing effect of SNP on the isolated ileum of the guinea pig
