title: Role of K+ channels and sodium pump in the vasodilation induced by acetylcholine, nitric oxide, and cyclic GMP in the rabbit aorta.
abstract: 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.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ferrer
authors.forename: J
authors.initials: J
authors.lastname: Marín
authors.forename: A
authors.initials: A
authors.lastname: Encabo
authors.forename: M J
authors.initials: MJ
authors.lastname: Alonso
authors.forename: G
authors.initials: G
authors.lastname: Balfagón
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D000109:Acetylcholine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester