AbstractThe vasorelaxing effect of benexate hydrochloride betadex (BHB) was examined in rat thoracic aortic ring with and without endothelium. BHB at 1∼100 μM caused concentrationdependent vasorelaxation in both endothelium‐intact and ‐denuded aortas precontracted with phenylephrine (1 μM), with its relaxing effect being significantly more potent in the endotheliumintact aorta. This partial endothelium‐dependent vasorelaxation by BHB was significantly inhibited by Nω‐nitro‐L‐arginine methylester (100 μM), an inhibitor of nitric oxide (NO) synthase, and hemoglobin (10 μM), an NO scavenger, but not by indomethacin (5 μM), an inhibitor of cyclooxygenase. The content of c‐GMP, a second messenger of NO, in endothelium‐intact aorta treated with BHB (30 μM) significantly increased by about twofold of the control level. NO synthase (NOS) activity by the treatment of BHB at 100 μM increased to about the same level by the treatment of L‐arginine at 10 μM. Taken together, these results suggest that the vasorelaxing effect of BHB is, in part, associated with NO synthesis and release from the endothelium but not with the prostaglandin system. The mechanism of NO synthesis and release from the endothelium by BHB might be NOS activation by the effect as a substrate of NOS. © 1995 Wiley‐Liss, Inc.