N‐substituted analogues of S‐nitroso‐<scp><i>N</i></scp>‐acetyl‐<scp>D</scp>,<scp>L</scp>‐penicillamine: chemical stability and prolonged nitric oxide mediated vasodilatation in isolated rat femoral arteries

Megson, Ian L.; Morton, Sarah; Greig, Iain R.; Mazzei, Francesca; Field, Robert A.; Butler, Anthony R.; Caron, Giulia; Gasco, Alberto; Fruttero, Roberta; Webb, David J.

doi:10.1038/sj.bjp.0702346

Cited by 48 publications

(46 citation statements)

References 43 publications

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“…Some nitric oxide (NO) donors such as sodium nitroprusside (SNP) or low-molecular weight (LMW) S-nitrosothiols (RSNO) cause long-lasting vasodilatation in vitro (after washing out the drug) or in vivo (after drug elimination) (Kanagy et al, 1996;Megson et al, 1997Megson et al, , 1999da SilvaSantos and Assreuy, 1999;Sogo et al, 2000;Terluk et al, 2000). It is unlikely that these long-lasting effects were primarily due to immediate activation of soluble guanylyl cyclase by the free radical NO.…”

mentioning

confidence: 99%

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

Alencar

Lobysheva²,

Chalupský³

et al. 2003

J Pharmacol Exp Ther

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The ability of various nitric oxide (NO) donors to induce longlasting 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 M of each compound. The S-nitrosating agents S-nitrosoglutathione (GSNO), S-nitroso-N-acetylpenicillamine, S-nitroso-N-acetylcysteine, and sodium nitroprusside (1 M) 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 M 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 M GSNO, but not to 100 M 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. SNitrosating 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.Some nitric oxide (NO) donors such as sodium nitroprusside (SNP) or low-molecular weight (LMW) S-nitrosothiols (RSNO) cause long-lasting vasodilatation in vitro (after washing out the drug) or in vivo (after drug elimination)

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mentioning

confidence: 99%

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

Alencar

Lobysheva²,

Chalupský³

et al. 2003

J Pharmacol Exp Ther

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“…It has been found to be more effective than SNAP at inducing vasodilatation in vitro, particularly in the presence of damaged endothelium [10]. Further modifications of RIG200 (longer lipophilic side chains) have improved its ability to elicit vascular relaxation in vitro [11].…”

Section: Rsnos As Drugsmentioning

confidence: 98%

Potential therapeutic uses for S-nitrosothiols

Richardson

Benjamin

2001

Clinical Science

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The S-nitrosothiols (RSNOs) are thought to represent a circulating endogenous reservoir of nitric oxide (NO), and may have potential as donors of NO, distinct from currently used agents. They have the general formula RSNO, and naturally occurring examples include S-nitrosocysteine, S-nitrosoglutathione and S-nitrosoalbumin, in which R is an amino acid, polypeptide and protein respectively. RSNOs have anti-platelet properties, a theoretical role in the treatment of asthma and the potential to be used as agents to treat infectious diseases ranging from the common cold to AIDS. RSNOs are relatively unstable, being degraded to release NO and the corresponding disulphide. Their stability is influenced by the properties of the R group, heat, light, the presence of transition metal ions (in particular copper) and the presence of other thiols. RSNOs participate in transnitrosation reactions in which the -NO group is transferred to another thiol to form a more stable RSNO. Thus the stability of RSNOs in vivo is difficult to predict, and this has led to the development of more stable analogues, in which the properties of R are modified. Potential interactions of RSNOs include that with ascorbic acid (vitamin C), which enhances the ability of copper to catalyse their degradation. Transnitrosation reactions with thiol-containing enzymes can influence protein function, and the intracellular thiol glutathione, levels of which are influenced by many disease states, can also influence stability. Thus, although RSNOs have many theoretically useful properties, there are also many aspects of their biochemistry that need to be addressed before their therapeutic potential can be fully realized.

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“…The decomposition of SNAP is increased by the presence of glutathione (Ferrero et al1999) and trace copper ions (Megson et al 1999), both of which may be released from cells following balloon injury. SPER/NO decomposes spontaneously with a long half-life (Blanchard et al 2001).…”

Section: Vascular Relaxation and No Releasementioning

confidence: 99%

Nitric Oxide Generation by NO Donors Is Enhanced Following Balloon Injury in the Porcine Coronary Artery

et al. 2007

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Vasospasm is a complication of cardiological procedures such as balloon angioplasty and may be related to vascular oxidant stress. Although nitric oxide donor drugs are often administered to prevent vasospasm, the response to these drugs in balloon-injured arteries has not been studied. Pig coronary arteries were balloon-injured in vitro and relaxations to nitric oxide (NO)-donating and NO-independent vasodilators studied. Generation of superoxide in response to injury was assayed using dihydroethidium. NO formation on addition of the NO donor drugs was studied using an amperometric sensor. Expression of nitrotyrosine, a peroxynitrite marker, was probed using immunocytochemistry. In vitro injury enhanced sensitivity to the NO donors SNAP and SpermineNONOate but blunted the response to isoprenaline or chromakalim. With both donors, NO formation was significantly enhanced in the presence of an injured vessel. Vascular superoxide generation was also increased throughout the vessel wall and a small increase in nitrotyrosine was detected in the injured vessel media following addition of SNAP. In conclusion, injured vessels were more sensitive to NO donors and this appears to be due to enhanced NO generation by the donor molecule. Increased formation of peroxynitrite within the injured vessel may contribute to the enhanced relaxation in injured vessels.

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N‐substituted analogues of S‐nitroso‐N‐acetyl‐D,L‐penicillamine: chemical stability and prolonged nitric oxide mediated vasodilatation in isolated rat femoral arteries

Cited by 48 publications

References 43 publications

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

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

Potential therapeutic uses for S-nitrosothiols

Nitric Oxide Generation by NO Donors Is Enhanced Following Balloon Injury in the Porcine Coronary Artery

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