The potassium channel-opening and vasorelaxant profiles of YM099, a newly synthesized benzoxadiazol derivative K channel opener, were evaluated in vitro. In the rat isolated portal vein, YM099 and a benzopyran derivative K channel opener levcromakalim concentration-dependently inhibited the frequency of spontaneous rhythmic contractions, with IC50 values of 104 and 38 nM, respectively. In the rabbit isolated aorta, YM099 (10(-7)-3 x 10(-5) M) and levcromakalim (10(-7)-3 x 10(-5) M) also concentration-dependently relaxed the contractions induced by 20 mM KCl, but they were ineffective against the contractions induced by 50 mM KCl. These effects of YM099 and levcromakalim were competitively antagonized by a K channel blocker glibenclamide (10(-7)-3 x 10(-6) M). In the rabbit isolated aorta, YM099 (3 x 10(-8)-3 x 10(-6) M), but not the calcium antagonist nifedipine (10(-8)-3 x 10(-6) M), relaxed the contractions induced by norepinephrine (10(-6) M) or prostaglandin F2 alpha (3 x 10(-6) M). These vasorelaxant effects of YM099 were also antagonized by glibenclamide. In conclusion, YM099 is a potent vascular smooth muscle-relaxant agent and possesses a vasorelaxant effect different from that of nifedipine. These effects of YM099 may be mediated, like those of levcromakalim, by the opening of glibenclamide-sensitive K channels.