Formation of releasable NO stores by S-nitrosoglutathione in arteries exhibiting tolerance to glyceryl-trinitrate.
S-Nitrosating nitric oxide (NO) donors like S-nitrosoglutathione (GSNO) induce a persistent inhibition of vascular tone, through the formation of releasable NO stores. In this study, we investigate whether GSNO also induces NO stores-related effects in vessels exhibiting tolerance to glyceryl-trinitrate. Rat aortic rings treated with glyceryl-trinitrate (100 microM for 1 h) exhibited increased level of superoxide and a decrease in NO elevation and relaxation induced by subsequent addition of glyceryl-trinitrate. In glyceryl-trinitrate-treated rings as in controls, pre-exposure to GSNO (1 microM for 30 min) induced a persistent hyporesponsiveness to noradrenaline and a relaxant response to N-acetylcysteine (a low molecular weight thiol which can displace NO from NO stores), both of which being inhibited by guanylyl-cyclase or cyclic GMP-dependent protein kinase inhibitors. These data indicate that GSNO can promote the formation of releasable NO stores in arteries exhibiting increased superoxide level and tolerance to glyceryl-trinitrate. Formation of releasable NO stores is of potential interest to restore the protective effect of NO in organic nitrate-tolerant blood vessels.
Sarr
Mamadou
M
Pharmacologie and Physico-Chimie, UMR CNRS 7034, Illkirch, France.
Lobysheva
Irina
I
Diallo
Aminata S
AS
Stoclet
Jean-Claude
JC
Schini-Kerth
Valérie B
VB
Muller
Bernard
B
D000111:Acetylcysteine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004048:Diethylamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009589:Nitrogen Oxides; D005996:Nitroglycerin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004048:Diethylamines; D009589:Nitrogen Oxides; D010069:Oxadiazoles; D011810:Quinoxalines; D013873:Thionucleotides; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; C087229:diethylamine dinitric oxide adduct; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D006152:Cyclic GMP; D000111:Acetylcysteine; D009638:Norepinephrine