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 rabbit 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+ (BK(Ca)) channels with charybdotoxin (ChTx), or voltage-dependent K+ (Kv) channels with 4-aminopyridine (4-AP). ACh relaxation was unaltered by glibenclamide, apamin, and Ba2+, blockers of ATP-sensitive K+ channels, small-conductance Ca2+-activated K+ channels, and inward rectifier K+ channels, respectively. The relaxation induced by exogenous NO and 8-bromocyclic GMP (8-BrcGMP) was similar in intact and endothelium-denuded segments, and it was reduced or unaltered by the same drugs used in the case of ACh. However, a 4-AP concentration 20-fold higher was necessary to reduce exogenous NO relaxation. These data suggest a resemblance in the mechanisms implicated in the relaxation elicited by ACh, exogenous NO, and 8-BrcGMP. Therefore, the relaxation caused by ACh is mainly mediated by endothelial NO, which in turn, enhances cGMP levels; this messenger appears to be the major one responsible for the smooth muscle cell hyperpolarization in the relaxation elicited by ACh, which is mediated by activation of the Na+ pump and ChTx- and 4-AP-sensitive K+ channels, likely BK(Ca) and Kv channels.