The hypotensive and vasorelaxant effect of dioclein in resistance mesenteric arteries was studied in intact animals and isolated vessels, respectively.In intact animals, initial bolus administration of dioclein (2.5 mg kg−1) produced transient hypotension accompanied by an increase in heart rate. Subsequent doses of dioclein (5 and 10 mg kg−1) produced hypotensive responses with no significant change in heart rate. NG-nitro-L-arginine methyl ester (L-NAME) did not affect the hypotensive response.In endothelium-containing or -denuded vessels pre-contracted with phenylephrine, dioclein (5 and 10 mg kg−1 produced a concentration-dependent vasorelaxation (IC50=0.3±0.06 and 1.6±0.6 μM, respectively) which was not changed by 10 μM indomethacin. L-NAME (300 μM) produced a shift to the right.Dioclein was without effect on contraction of vessels induced by physiological salt solution (PSS) containing 50 mM KCl and the concentration dependence of dioclein's effect on phenylephrine induced contraction was shifted to the right in vessels bathed in PSS containing 25 mM KCl.Tetraethylammonium (10 mM) and BaCl2 (1 mM) increased the IC50 for dioclein-induced vasorelaxation without affecting the maximal response (Emax). Charybdotoxin (100 nM), 4-aminopyridine (1 mM) and iberiotoxin (100 nM) increased the IC50 and reduced the Emax. Apamin (1 μM) reduced the Emax without affecting the IC50.Dioclein produced a hyperpolarization in smooth muscle of mesenteric arteries with or without endothelium (7.7±1.4 mV and 12.3±3.6 mV, respectively).In conclusion dioclein lowered arterial pressure probably through a decrease in peripheral vascular resistance. The underling mechanism implicated in the vasorelaxant effect of dioclein appears to be the opening of KCa and Kv channels and subsequent membrane hyperpolarization.