Received for publication April 4, 2003.
Revised April 23, 2003.
Accepted for publication June 17, 2003.

S-nitrosating NO donors induce long-lasting inhibition of contraction in isolated arteries

Abstract

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 which persisted after removal of the drug. This hyporesponsiveness to NE was associated with a relaxant effect of N-acetylcysteine (NAC), a low molecular weight thiol which 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 using an anti-cysteine-NO antiserum). The GSNO-induced increase in cysteine-NO residues in aortic tissue was prevented by the thiol modifying 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.

Key words: N-acetylcysteine, NO donors, S-nitrosation, arteries, contraction, nitric oxide

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