The endothelial lining of blood vessels plays an important role in the control of arterial tone by releasing a number of vasoactive factors. Among these, nitric oxide (NO) or a NO containing moiety, some cyclooxygenase products such as prostacyclin (PGl2) and a still hypothetical hyperpolarizing factor may induce dilatation/relaxation. In the present study, the functional importance of these factors in mediating endothelium-dependent relaxation has been investigated in isolated cerebral arteries. Acetylcholine (ACh) was used to induce endothelium-dependent relaxation of ring segments obtained from rat and rabbit basilar artery (BA). Glibenclamide (10(-6) M) which acts as an inhibitor of ATP-sensitive K+ channel activation did not affect the relaxant action of ACh. With the cyclooxygenase blocked by indomethacin (10(-6) M) ACh-induced relaxation was unaffected in rat BA and only slightly attenuated in rabbit BA. The NO synthase inhibitor NG-nitro-L-arginine (L-NNA, 10(-6) and 10(-5) M) completely abolished ACh-induced relaxation in rat BA and resulted in a moderate inhibition in rabbit BA (10(-5) and 10(-4) M). However, ACh-induced relaxation of rabbit BA was abolished in the presence of both indomethacin and L-NNA. These results indicate that endothelium-dependent relaxation of large cerebral arteries is mediated by NO acting alone or in concert with a relaxant cyclooxygenase product. In addition, there is no indication for the action of an endothelium-derived hyperpolarizing factor different from NO or a prostanoid.