Role of Gap-Junctions in Endothelium-Dependent Hyperpolarization in Rat Small and Large Mesenteric Arteries

P39 In arteries, acetylcholine (ACh) releases endothelium-derived hyperpolarizing factor (EDHF) which is distinct from nitric oxide. The identity of EDHF is still elusive; however several recent studies suggests the possible involvement of myoendothelial gap-junctions in small arteries. To elucidate the involvement of gap-junctions in EDHF responses, we examined the effects of 18α-glycyrrhetinic acid (18α-GA, 10 -4 mol/L), a gap junction inhibitor, on endothelium-dependent hyperpolarization and relaxation to ACh in rat small and large mesenteric arteries. Experiments were perfomed in the presence of indomethacin (10 -5 mol/L) and NG-nitro-L-arginine (10 -4 mol/L) . In large arteries, ACh (10 -6 mol/L)-induced hyperpolarization measured from intimal side, was attenuated by the 18α-GA (12.4±1.2 vs. 8.4±0.8mV in the absence and presence of 18α-GA, p -7 mol/L), ACh-induced relaxation was also attenuated (maximal relaxation, 71.5±6.3 vs. 50.5±6.4%, p + -channels, did not differ in the absence and presence of 18α-GA (16.7±0.6 vs. 16.3±1.5mV, ns, n=8 and n=6 respectively). These findings suggest that myoendothelial gap-junctions partly contribute to the EDHF-mediated responses both in rat small and large mesenteric arteries.