It has been reported that 3-(([2-(3,4-dimethoxyphenyl)ethyl]carbamoyl)methyl)amino-N-methylbenz amide (DQ-2511: ecabapide) effectively increases gastric mucosal blood flow in rats, suggesting that this property may contribute to the antiulcer activity. To clarify the mechanisms underlying the increase in gastric mucosal blood flow, we investigated the dilator response of rat isolated thoracic aorta, mesenteric artery and celiac artery smooth muscle preparations to DQ-2511. This compound prevented noradrenaline-induced contraction in both the presence and absence of endothelium in the arterial specimen, and it (0.01-1 mM) inhibited these contractions induced by noradrenaline in all tissues in a concentration-dependent manner. This inhibitory effect of DQ-2511 was most evident in the celiac artery. The dilator response to DQ-2511 (0.1 mM) was abolished after pretreatment with methylene blue (3 microM), a guanylate cyclase inhibitor. Under the same conditions, methylene blue inhibited the dilator response to acetylcholine (1 microM), but not that to papaverine (10 microM). Furthermore, when DQ-2511 (0.01-1 mM) was incubated with the arterial preparations, this compound increased cyclic GMP content in segments in a concentration-dependent manner. These findings demonstrate that the vasodilation induced by DQ-2511 is independent of the endothelium and is related to the augmentation of intracellular cyclic GMP content, which may consequently contribute to the increased gastric mucosal blood flow.