It has been reported that endothelium-derived relaxing factor (EDRF) possesses chemical and pharmacological properties that are indistinguishable from those of nitric oxide (NO). Moreover, NO is the active chemical species responsible for endothelium-independent vasodilation produced by nitrogen oxide-containing substances including glyceryl trinitrate (GTN). Both EDRF and GTN activate soluble guanylate cyclase and consequently increase cyclic GMP level in various artery preparations. However, there have been few reports regarding cyclic GMP accumulation induced by EDRF or GTN in canine cerebral arteries. Therefore, it was investigated whether EDRF and GTN cause vasodilation through the common pathway mediated by cyclic GMP in the canine basilar artery. The relaxation responses induced by EDRF or GTN were studied in the canine basilar artery by an isometric tension-recording method. EDRF was induced by calcium ionophore A 23187. A 23187 did not relax the vascular tissue in the absence of the endothelial cells. On the other hand, GTN did induce relaxation in either the presence or absence of endothelial cells. FeSO4 at 3 X 10(-5) M reversed A23187-induced relaxation, but not GTN-induced relaxation (N = 10). Since Fe2+ is able to catalyse the formation of O2- in oxygenated phosphate buffer, these findings suggest that Fe2+ antagonizes EDRF by inactivating it via the generation of O2-. By the addition of 10(-5) M methylene blue, both A 23187- and GTN-induced relaxations were reversed (N = 8). Moreover, pretreatment with 10(-5) M methylene blue augmented contractile responses to 3 X 10(-6) M prostaglandin F2 alpha (N = 5).(ABSTRACT TRUNCATED AT 250 WORDS)