Hyperpolarization-induced dilatation of submucosal arterioles in the guinea-pig ileum

1 The effects of inhibition of acetylcholine (ACh)-induced hyperpolarization on dilatation of submucosal arterioles were investigated in the guinea-pig ileum. 2 In smooth muscles of the arterioles depolarized by Ba2+ (0.5 mM) to about -40 mV, ACh (3 muM) repolarized the membrane to about -65 mV (hyperpolarization), irrespective of the absence or presence of L-N-omega-nitroarginine (L-NOARG, 0.1 mM) and diclofenac (1 muM), and increased the diameter (dilatation). 3 Combined application of charybdotoxin (CTX, 50 nM) and apamin (0.1 muM), inhibitors of some types of K+-channels, abolished the ACh-induced hyperpolarization and dilatation. 4 18 beta -Glycerrhetinic acid (18 beta -GA, 30 muM), a known inhibitor of gap junctions, depolarized the membrane to about -36 mV, either in the absence or in the presence of Ba2+, with no associated contraction of the arterioles. In the presence of 18 beta -GA, ACh-induced hyperpolarization was abolished, however the dilatation was inhibited only partially, with associated inhibition of constriction produced by Ba2+ and NA. 5 18 beta -GA inhibited the dilatation produced by sodium nitroprusside, an NO donor. 6 The ACh-induced hyperpolarization and dilatation were abolished in the presence of 2-aminoethoxydiphenyl berate (30 muM), an inhibitory modulator of inositol trisphosphate receptor-mediated Ca2+ release from intracellular stores. 7 It is concluded that in submucosal arterioles, hyperpolarizations produced by ACh have causal relationship to the arteriolar dilatation. 18 beta -GA did not induce parallel relationship between hyperpolarization and dilatation produced by ACh. 18 beta -GA may have unidentified inhibitory effects on agonist-mediated actions, in addition to the inhibition of gap junctions.