THE IMPORTANCE OF THE HYPERPOLARIZING MECHANISM INCREASES AS THE VESSEL SIZE DECREASES IN ENDOTHELIUM-DEPENDENT RELAXATIONS IN RAT MESENTERIC CIRCULATION

Endothelium-dependent relaxations are achieved by a combination of end othelium-derived prostacyclin (PGI(2)), nitric oxide (NO), and endothe lium-derived hyperpolarizing factor (EDHF). However, it remains to be fully clarified whether the relative contribution of these three mecha nisms to endothelium-dependent relaxations varies as a function of the vessel size. This study was designed to clarify this point. Acetylcho line (ACh)-induced endothelium-dependent relaxations were examined in isolated blood vessels taken from the aorta and the proximal and dista l mesenteric arteries of the rat. The contributions of PGI(2), NO, and EDHF were evaluated by the inhibitory effects of indomethacin, N-omeg a-nitro-L-arginine methyl ester (L-NAME) in the presence of indomethac in, and KCI in the presence of indomethacin and L-NAME, respectively. The membrane potentials were recorded with microelectrodes. The expres sion of endothelial NO synthase (eNOS) was examined by both immunostai ning and immunoblotting. The contribution of PGI(2) was negligible in three different-sized blood vessels. The contribution of NO was most p rominent in the aorta, whereas that of EDHF was most prominent in the distal mesenteric arteries. The resting membrane potential was signifi cantly deeper and the ACh-induced hyperpolarization was greater in the distal mesenteric arteries than those in the aorta. The expression of eNOS was the highest in the aorta and the lowest in the distal mesent eric arteries. These results indicate that the importance of EDHF incr eases as the vessel size decreases in endothelium-dependent relaxation s in the rat mesenteric circulation.