S-nitrosating nitric oxide donors induce long-lasting inhibition of contraction in isolated arteries.
The ability of various nitric oxide (NO) donors to induce long-lasting inhibition of contraction in isolated arteries was compared. All the studied compounds elicited a relaxant effect in rat aortic rings precontracted with norepinephrine (NE). Almost maximal relaxation was obtained with 1 microM of each compound. The S-nitrosating agents S-nitrosoglutathione (GSNO), S-nitroso-N-acetylpenicillamine, S-nitroso-N-acetylcysteine, and sodium nitroprusside (1 microM) produced a decrease of the maximal effect of NE that persisted after removal of the drug. This hyporesponsiveness to NE was associated with a relaxant effect of N-acetylcysteine, a low-molecular weight thiol that can displace NO from cysteine-NO bonds. Such modifications of contraction were not observed in aortic rings previously exposed to 1 microM S-nitrosocysteine, glyceryl trinitrate, 3-morpholinosydnonimine, or 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NO). The same differential effects of GSNO and DEA-NO on contraction were also observed in porcine coronary arteries. Rat aortic rings previously exposed to 100 microM GSNO, but not to 100 microM DEA-NO, displayed a persistent increase in NO content (determined by NO spin trapping) and cysteine-NO residues (determined by immunostaining with an anti-cysteine-NO antiserum). The GSNO-induced increase in cysteine-NO residues in aortic tissue was prevented by the thiolmodifying agent p-hydroxymercuribenzoic acid. This study shows that in isolated arteries, the effects of S-nitrosating agents differed from those of other NO-donating agents. S- Nitrosating agents induced a persistent inhibition of contraction, which was attributed to the formation of releasable NO stores by S-nitrosation of tissue thiols. These differential effects of NO donors may be important for orientating their therapeutic indications.
Alencar
Jacicarlos L
JL
Université Louis Pasteur, Faculté de Pharmacie, Pharmacologie and Physico-Chimie, Unité Mixte Recherche Centre National de la Recherche Scientifique, Illkirch, France.
Lobysheva
Irina
I
Chalupsky
Karel
K
Geffard
Michel
M
Nepveu
Françoise
F
Stoclet
Jean-Claude
JC
Muller
Bernard
B
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006834:Hydrazines / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D020030:Nitric Oxide Donors / Q000378:metabolism / Q000494:pharmacology*; D009589:Nitrogen Oxides; D051381:Rats; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine / Q000378:metabolism / Q000494:pharmacology; D026422:S-Nitrosoglutathione / Q000378:metabolism / Q000494:pharmacology; D026403:S-Nitrosothiols / Q000378:metabolism / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D006834:Hydrazines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D026422:S-Nitrosoglutathione; D026423:S-Nitroso-N-Acetylpenicillamine; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; C021315:S-nitrosocysteine; D003545:Cysteine