Critical role of gap junctions in endothelium-dependent hyperpolarization in rat mesenteric arteries

1. Acetylcholine (ACh) evokes endothelium-dependent hyperpolarization in arterial cells, presumably through endothelium-derived hyperpolarizing factor (EDHF). The identity of EDHF is still elusive; however, several recent studies suggest the possible involvement of myoendothelial gap junctions in the EDHF response. 2. To elucidate the role of gap junctions in endothelium-dependent hyperpolarization, we examined the effects of the gap junction inhibitors 18 alpha-glycyrrhetinic acid (18 alpha-GA; 10(-4) mol/L) and carbenoxolone (3 x 10(-4) mol/L), a water-soluble form of 18 beta-GA, on hyperpolarization and relaxation to ACh in rat proximal and distal mesenteric arteries. Experiments were performed in the presence of indomethacin (10(-5) mol/L) and N(G)-nitro-L-arginine (10(-4) mol/L). 3. In both proximal and distal mesenteric arteries, ACh-induced hyperpolarization and relaxation were partially inhibited by 18 alpha-GA and abolished by carbenoxolone. 4. Endothelium-independent hyperpolarization to levcromakalim, an ATP-sensitive K+ channel opener, were unaffected by 18 alpha-GA or carbenoxolone in both arteries. 5. Relaxations to levcromakalim were unaffected by 18 alpha-GA, but were inhibited somewhat by carbenoxolone in proximal mesenteric arteries. 6. These findings suggest that myoendothelial gap junctions play a critical role in EDHF-mediated responses in both proximal and distal mesenteric arteries of the rat.