S-Nitrosating Nitric Oxide Donors Induce Long-Lasting Inhibition of Contraction in Isolated Arteries

• Published in: The Journal of pharmacology and experimental therapeutics 2003-10, Vol.307 (1), p.152-159
• Main Authors: Alencar, Jacicarlos L, Lobysheva, Irina, Chalupsky, Karel, Geffard, Michel, Nepveu, Françoise, Stoclet, Jean-Claude, Muller, Bernard
• Format: Article
• Language: English
• Subjects: Animals; Aorta - drug effects; Aorta - physiology; Arteries - drug effects; Arteries - physiology; Cysteine - analogs & derivatives; Cysteine - metabolism; Cysteine - pharmacology; Hydrazines - metabolism; Hydrazines - pharmacology; Male; Nitric Oxide Donors - metabolism; Nitric Oxide Donors - pharmacology; Nitrogen Oxides; Rats; Rats, Wistar; S-Nitroso-N-Acetylpenicillamine - metabolism; S-Nitroso-N-Acetylpenicillamine - pharmacology; S-Nitrosoglutathione - metabolism; S-Nitrosoglutathione - pharmacology; S-Nitrosothiols - metabolism; S-Nitrosothiols - pharmacology; Swine; Vasoconstriction - drug effects; Vasodilator Agents - metabolism; Vasodilator Agents - pharmacology
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.103.052605

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 μM of each compound. The S -nitrosating agents S- nitrosoglutathione (GSNO), S -nitroso- N -acetylpenicillamine, S -nitroso- N -acetylcysteine, and sodium nitroprusside (1 μM) 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 μM 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 μM GSNO, but not to 100 μM 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.