title: The relaxation induced by S-nitroso-glutathione and S-nitroso-N-acetylcysteine in rat aorta is not related to nitric oxide production.
abstract: S-nitroso-glutathione (GSNO) and S-nitroso-N-acetylcysteine (NACysNO) are nitrosothiols that release nitric oxide (NO) and mimic the effects of endogenous NO. This study investigated the relaxation induced by GSNO and NACysNO in rat aorta and the relation between relaxation and NO formation. Both compounds at concentrations from 10(-9) M to 10(-4) M relaxed the rat aorta in a concentration-dependent manner. However, NO production depended on the concentration of nitrosothiols present and was detected only above 100 microM GSNO or NACysNO. To determine whether K+ channels are involved in the relaxation induced by nitrosothiols, the contractions were induced with KCl at concentrations of 30, 60, or 90 mM. The concentration-effect curves for the relaxation induced by nitrosothiols were shifted to the right for all the K+ concentrations compared with aortas precontracted with phenylephrine. These results indicate the participation of K+ channels in the relaxation induced by GSNO and NACysNO. A selective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, significantly inhibited the relaxation induced by the nitrosothiols. The relaxation induced by GSNO and NACysNO was inhibited by the K+ channel blockers glibenclamide, selective K(ATP) channels, and apamin, selective for low-conductance Ca2+-activated K+ channels in rat aorta, but was not inhibited by charybdotoxin, a potent and selective Ca2+-activated K+ channel blocker, or by 4-aminopyridine, a voltage-gated K+ channel blocker. These results indicate that relaxation induced by GSNO and NACysNO is partially due to activation of K(ATP) channels and partially due to activation of low-conductance Ca2+-activated K+ channels. However, the ability of the nitrosothiol compounds to overcome the inhibitory effect of high extracellular K+ concentrations suggests another mechanism of relaxation contributing to the nitrosothiol response. The most intriguing finding is that relaxation is not related to the NO produced in rat aorta.
authors.affiliation: Department of Chemistry of Faculty of Philosophy Science and Letters of Ribeirão Preto (FFCLRP), University of São Paulo, São Paulo, Brazil.
authors.forename: P I
authors.initials: PI
authors.lastname: Ceron
authors.forename: D C
authors.initials: DC
authors.lastname: Cremonez
authors.forename: L M
authors.initials: LM
authors.lastname: Bendhack
authors.forename: A C
authors.initials: AC
authors.lastname: Tedesco
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D009603:Nitroso Compounds / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011189:Potassium Chloride / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D026422:S-Nitrosoglutathione; D019284:Thapsigargin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D014662:Vasoconstrictor Agents; D012433:Ryanodine; D010656:Phenylephrine; D009569:Nitric Oxide; C024940:S-nitroso-N-acetylcysteine; D026422:S-Nitrosoglutathione; D011189:Potassium Chloride; D019284:Thapsigargin; D005978:Glutathione; D000111:Acetylcysteine