Comparative pharmacology of analogues of S‐nitroso‐<i>N</i>‐acetyl‐<scp>dl</scp>‐penicillamine on human platelets

Salas, Eduardo; Moro, Marı́a A.; Askew, Stuart C.; Hodson, H. F.; Butler, Anthony R.; Radomski, Marek W.; Moncada, Salvador

doi:10.1111/j.1476-5381.1994.tb13192.x

Cited by 48 publications

(20 citation statements)

References 25 publications

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“…3-Morpholino-sydnonimine (SIN-1) an active metabolite of the anti-anginal drug molsidomine, has been shown to release NO together with superoxide anion (02-) (Feelisch, 1991;Hogg et al, 1992). Recently, some chemically different compounds have been reported to release NO directly or indirectly (Maragos et al, 1991;Feelisch et al, 1992;Mulsch et al, 1993;Medana et al, 1994;Kita et al, 1994;Salas et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide‐donating properties of mesoionic 3‐aryl substituted oxatriazole‐5‐imine derivatives

Kankaanranta

Rydell

Petersson

et al. 1996

British J Pharmacology

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1 The nitric oxide (NO)-releasing properties of two new mesoionic 3-aryl substituted oxatriazole-5-imine derivatives (GEA 3162 and GEA 3175) were characterized and compared with the known NOdonors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). 2 GEA 3162, GEA 3175, SIN-i and SNAP inhibited adenosine 5'-diphosphate-induced platelet aggregation (IC50 values 0.18, 0.39, 3.73 and 2.12 gM, respectively). All four compounds induced a dosedependent and more than 4 fold increase in cyclic GMP in platelets. The increase in cyclic GMP concentration was potentiated more than 1.5 fold by a phosphodiesterase inhibitor, zaprinast (10 gM) and inhibited 38-97% by oxyhaemoglobin (10-45 gM).3 All of the four compounds studied converted oxyhaemoglobin to methaemoglobin and formed a paramagnetic NO-haemoglobin complex. All but GEA 3175 formed nitrite and nitrate in phosphate buffer. During a 40 min incubation, GEA 3162, SIN-I and SNAP (100 pM) produced 50-70 gM NO2-+ NO3-as determined by high performance liquid chromatography. The release of NO and NO2 by GEA 3175 was increased 140 fold in the presence of human plasma (0.14 and 19.7 ppb in the absence and presence of 1% human plasma, respectively) as analyzed by ozone chemiluminescence. 4 The results suggest that the mesoionic 3-aryl substituted oxatriazole-5-imine derivatives GEA 3162 and GEA 3175 as well as SIN-l and SNAP release nitric oxide.

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Section: Introductionmentioning

confidence: 99%

Nitric oxide‐donating properties of mesoionic 3‐aryl substituted oxatriazole‐5‐imine derivatives

Kankaanranta

Rydell

Petersson

et al. 1996

British J Pharmacology

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“…However, apyrase and 2-MeSAMP did not exert significant effects on platelet microaggregation, indicating that release of ADP from platelets does not significantly contribute to generation of platelet microaggregates under the experimental conditions used. Prostacyclin and NO are important platelet inhibitors generated from the endothelium that synergize to regulate platelet activation; 31 therefore, prostacyclin and two NOreleasing compounds, GSNO and SNAP, known to inhibit platelet aggregation, 29,30 were also tested. Prostacyclin was not only able to inhibit platelet aggregation but also caused disaggregation as monitored in real-time by the device, an effect similar to that measured by light aggregometry.…”

Section: Pharmacology Of Fibrinogen-induced Platelet Microaggregationmentioning

confidence: 99%

“…Since nitric oxide (NO) mediates major inhibitor pathways and regulates platelet GPIIb/IIIa receptor function, [26][27][28] we tested the effects of platelet-inhibitory NO-releasing agents such as SNAP 29 and GSNO. 30 Both compounds inhibited platelet aggregation, as reflected by reduced changes in f and D compared with the control and corroborated by optical microscopy (SNAP Dp=0.0005; SNAP fp=0.0011 and GNSO Dp=0.0005; fp=0.0017, n=4).…”

mentioning

confidence: 99%

Pharmacological characterization of nanoparticle-induced platelet microaggregation using quartz crystal microbalance with dissipation: comparison with light aggregometry

Santos-Martínez¹,

Tomaszewski²,

Medina³

et al. 2015

IJN

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Background Engineered nanoparticles (NPs) can induce platelet activation and aggregation, but the mechanisms underlying these interactions are not well understood. This could be due in part to use of devices that study platelet function under quasi-static conditions with low sensitivity to measure platelet microaggregation. Therefore, in this study we investigated the pharmacological pathways and regulators of NP-induced platelet microaggregation under flow conditions at nanoscale using quartz crystal microbalance with dissipation (QCM-D) and compared the data thus obtained with those generated by light aggregometry. Methods Blood was collected from healthy volunteers, and platelet-rich plasma was obtained. Thrombin receptor-activating peptide, a potent stimulator of platelet function, and pharmacological inhibitors were used to modulate platelet microaggregation in the presence/absence of silica (10 nm and 50 nm) and polystyrene (23 nm) NPs. Light aggregometry was used to study platelet aggregation in macroscale. Optical, immunofluorescence, and scanning electron microscopy were also used to visualize platelet aggregates. Results Platelet microaggregation was enhanced by thrombin receptor-activating peptide, whereas prostacyclin, nitric oxide donors, acetylsalicylic acid, and phenanthroline, but not adenosine diphosphate (ADP) blockers, were able to inhibit platelet microaggregation. NPs caused platelet microaggregation, an effect not detectable by light aggregometry. NP-induced microaggregation was attenuated by platelet inhibitors. Conclusion NP-induced platelet microaggregation appears to involve classical proaggregatory pathways (thromboxane A 2 -mediated and matrix metalloproteinase-2-mediated) and can be regulated by endogenous (prostacyclin) and pharmacological (acetylsalicylic acid, phenanthroline, and nitric oxide donors) inhibitors of platelet function. Quartz crystal microbalance with dissipation, but not light aggregometry, is an appropriate method for studying NP-induced microaggregation.

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“…These authors observed that PN (20 M-200 M), but not of decomposed PN, when added to washed platelet suspensions produced concentration-dependent increases in aggregation when measured by plateletionized calcium aggregometer [22]. The additions of platelet aggregation inhibitors such as SNAP, prostacyclin, or indomethacin [228,229] to the washed platelet suspensions had no significant effect on platelet aggregation induced by PN [22]. The addition of PN could also completely reverse the inhibitory effects of SNAP on collagen-induced platelet aggregation, whereas PN would significantly reverse (~50%) the antiaggregatory effects of indomethacin and of prostacyclin [22].…”

Section: Anti-platelet Aggregation Effects Of Peroxynitritementioning

confidence: 99%

Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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Peroxynitrite (PN) is generated by the reaction of nitric oxide (NO) and superoxide in one of the most rapid reactions in biology. Studies have reported that PN is a cytotoxic molecule that contributes to vascular injury in a number of disease states. However, it has become apparent that PN has beneficial effects including vasodilation, inhibition of platelet aggregation, inhibition of inflammatory cell adhesion, and protection against ischemia/reperfusion injury in the heart. It is our hypothesis that PN may serve to inactivate superoxide and prolong the actions of NO in the circulation. This manuscript reviews the beneficial effects of PN in the cardiovascular system. Keywords:Nitric oxide/*metabolism, nitric oxide synthase/metabolism/physiology, peroxynitrous acid/metabolism, reactive nitrogen species/metabolism, reactive oxygen species/metabolism, endothelium, vascular/drug effects/metabolism, muscle, smooth, vascular/drug effects/*metabolism, vasodilator agents/adverse effects, oxidative stress/*physiology, vasodilation/drug effects.

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Comparative pharmacology of analogues of S‐nitroso‐N‐acetyl‐dl‐penicillamine on human platelets

Cited by 48 publications

References 25 publications

Nitric oxide‐donating properties of mesoionic 3‐aryl substituted oxatriazole‐5‐imine derivatives

Nitric oxide‐donating properties of mesoionic 3‐aryl substituted oxatriazole‐5‐imine derivatives

Pharmacological characterization of nanoparticle-induced platelet microaggregation using quartz crystal microbalance with dissipation: comparison with light aggregometry

Potential Benefits of Peroxynitrite

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