[Role of endothelium-derived hyperpolarizing factor in shear stress-induced endothelium-dependent relaxations of rats].

AIM

To investigate the role and mechanism of endothelium-derived hyperpolarizing factor (EDHF) in shear stress induced vasorelaxation of rat mesenteric artery.

METHODS

The changes in vessel diameter in response to variable flow (0-300 microL.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.

RESULTS

The shear stress-induced relaxation were endothelium dependent and the contribution of NO was more prominent in large mesenteric arteries (400-500 microm) than that in resistance arteries (150-250 microm), 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.

CONCLUSION

EDHF plays an important role in shear stress-induced endothelium-dependent relaxations, and K channels especially calcium-activated K channels appear to be involved.