Abstract: AimTo investigate the role and mechanism of endothelium-derived hyperpolarizing factor (EDHF) in shear stress induced vasorelaxation of rat mesenteric artery. MethodsThe changes in vessel diameter in response to variable flow (0-300 μL·min^-1) were continuously examined. The contribution of prostacyclin (PGI₂), NO and EDHF to shear stress induced relaxation were analyzed by inhibitory effects of indomethacin, N^G-nitro-L-arginine (L-NA) and KCl. The nature and hyperpolarizing mechanism of EDHF were examined by the inhibitory effects of inhibitors of cytochrome P450 pathway and of various K⁺ channels. ResultsThe shear stress-induced relaxation were endothelium dependent and the contribution of NO was more prominent in large mesenteric arteries (400-500 μm) than that in resistance arteries (150-250 μm), whereas that of EDHF was noted in both-sized blood vessels. Tetrabutylammonium (a nonselective inhibitor of K channels) almost abolished, whereas the combination of charybdotoxin (an inhibitor of both large and intermediate-conductance Ca²⁺-activated K channels) and apamin (an inhibitor of small-conductance Ca²⁺-activated K channels) significantly inhibited the EDHF-mediated component of the shear stress-induced relaxations. ConclusionEDHF plays an important role in shear stress-induced endothelium-dependent relaxations, and K channels especially calcium-activated K channels appear to be involved.