Role of K+ channels and sodium pump in the vasodilation induced by acetylcholine, nitric oxide, and cyclic GMP in the rabbit aorta

The endothelium-dependent relaxation caused by acetylcholine (ACh) in rabbi t aorta segments was reduced by the nitric oxide (NO) synthase inhibitor N- G-nitro-L-arginine methyl ester and by blockade of: Na+ pump with ouabain, large-conductance Ca2+-activated K+ (BKCa) channels with charybdotoxin (ChT x), or voltage-dependent K+ (K-V) channels with 4-aminopyridine (4-AP). ACh relaxation was unaltered-by glibenclamide, apamin, and Ba2+, blockers of A TP-sensitive K+ channels, small-conductance Ca2+-activated K+ channels, and inward rectifier K+ channels, respectively. The relaxation induced by exog enous NO and 8-bromocyclic GMP (8-BrcGMP) was similar in intact and endothe lium-denuded segments, and it was reduced or unaltered by the same drugs us ed in the case of ACh. However, a 4-AP concentration 20-fold higher was nec essary to reduce exogenous NO relaxation. These data suggest a resemblance in the mechanisms implicated in the relaxation elicited by ACh, exogenous N O, and 8-BrcGMP. Therefore, the relaxation caused by ACh is mainly mediated by endothelial NO, which in turn, enhances cGMP levels; this messenger app ears to be the major one responsible for the smooth muscle cell hyperpolari zation in the relaxation elicited by ACh, which is mediated by activation o f the Na+ pump and ChTx- and 4-AP-sensitive K+ channels, likely BKCa and K- V channels. (C) 1999 Elsevier Science Inc. All rights reserved.