Role of Gap-Junctions in Endothelium-Dependent Hyperpolarization in Rat Small and Large Mesenteric Arteries
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, 10-4mol/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 (10-5mol/L) and NG-nitro-L-arginine (10-4mol/L) . In large arteries, ACh (10-6mol/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<0.05, n=7). In rings pre-contracted with norepinephrine (5×10-7mol/L), ACh-induced relaxation was also attenuated (maximal relaxation, 71.5±6.3 vs. 50.5±6.4%, p<0.05, n=8 ). In small arteries, ACh-induced hyperpolarization, measured from either adventitial side or intimal side was attenuated by 18α-GA (adventitial side, 12.3±1.2 vs. 4.6±0.7mV, p<0.05, n=8; intimal side, 8.0±0.7 vs. 5.0±0.7mV, p<0.05, n=4). On the other hand, smooth muscle hyperpolarization to levcromakalim, a direct activator of ATP-sensitive K+-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.