Vascular smooth muscle relaxation mediated by nitric oxide donors: a comparison with acetylcholine, nitric oxide andnitroxyl ion

Wanstall, Janet C.; Jeffery, Trina K.; Gambino, Agatha; Lovren, Fina; Triggle, Chris R.

doi:10.1038/sj.bjp.0704269

Cited by 114 publications

(126 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The NO 0 specie has been described to activate mainly sGC, while NO − specie could activate directly K + channels [7,37]. In addition, the present work shows that the amount and duration of NO 0 released by NO donor also determine its pharmacological properties.…”

Section: Resultssupporting

confidence: 53%

Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta

et al. 2014

View full text Add to dashboard Cite

Nitric oxide (NO) plays an important role on several biological functions. Recently, it has been reported the possibility of modifying the NO release profile from the NO donors through its coupling to gold nanoparticles (AuNPs). Thus, AuNPs were synthesized and they were exposed to the NO donor ruthenium complex Cis-[Ru(bpy) 2 (NO)(4PySH)].(PF6) 3 termed (Ru-4PySH)-forming AuNPs-{Ru-4PySH} n cluster. Our results indicate that AuNPs do not modify the maximum effect (ME) and potency (pD 2 ) in the vasodilation induced by Ru-4PySH. Both complexes induce similar vascular relaxation in concentration-dependent way. However, the NO released from the complex AuNPs-{Ru-4PySH} n is lower than Ru-4PySH. Both complexes release only NO 0 specie, but AuNPs-{Ru-4PySH} n releases NO in constant way and exclusively in the extracellular medium. In time-course, Ru-4Py-SH was faster than AuNPs-{Ru-4PySH} n in inducing the maximum vasodilation. Inhibition of soluble guanylyl cyclase (sGC) abolished the vasodilation induced by Ru-4PYSH, but not by AuNPs-{Ru-4PySH} n . Nonselective potassium (K + ) channel blocker TEA had no effect on the vasodilation induced by AuNPs-{Ru-4PySH} n , but it reduced the potency to Ru-4PySH. In conclusion, our results suggest that AuNPs can reduce the permeability of NO donor Ru-4PySH due to AuNPs-{Ru-4PySH} n cluster formation. AuNPs reduce NO release, but they do not impair the vasodilator effect induced by the NO donor. Ru-4PySH induces vasodilation by sGC and K + channels activation, while AuNPs-{Ru-4PySH} n activates mainly sGC. Taken together, these findings represent a new pharmacological strategy to control the NO release which could activate selective biological targets.

show abstract

Section: Resultssupporting

confidence: 53%

Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta

et al. 2014

View full text Add to dashboard Cite

show abstract

“…These results indicate that a significant portion of the relaxation induced by these reaction products is mediated by an alternative mechanism, which may directly activate sGC without releasing free NO. These effects of cPTIO and ODQ on the products of the Sulfide/GSNO interaction are reminiscent of reports on effects of the HNO donor Angeli's salt (AS) [43][44][45]. This suggests that HNO may be involved in the relaxation effects induced by the 'SSNO -mix'.…”

Section: Modulation Of the Relaxation Effect Of The 'Ssno -Mix' And Gsnomentioning

confidence: 59%

The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

et al. 2015

View full text Add to dashboard Cite

A B S T R A C TThe chemical interaction of sodium sulfide (Na2S) with the NO-donor S-nitrosoglutathione (GSNO) has been described to generate new reaction products, including polysulfides and nitrosopersulfide (SSNO -) via intermediacy of thionitrous acid (HSNO). The aim of the present work was to investigate the vascular effects of the longer-lived products of the Sulfide/GSNO interaction. Here we show that the products of this reaction relax precontracted isolated rings of rat thoracic aorta and mesenteric artery (but to a lesser degree rat uterus) with a >2-fold potency compared with the starting material, GSNO (50 nM), whereas Na2S and polysulfides have little effect at 1-5 μM. The onset of vasorelaxation of the reaction products was 7-10 times faster in aorta and mesenteric arteries compared with GSNO. Relaxation to GSNO (100-500 nM) was blocked by an inhibitor of soluble guanylyl cyclase, ODQ (0.1 and 10 μM), and by the NO scavenger cPTIO (100 μM), but less affected by prior acidification (pH 2-4), and unaffected by N-acetylcysteine (1 mM) or methemoglobin (20 μM heme). By contrast, relaxation to the Sulfide/GSNO reaction products (100-500 nM based on the starting material) was inhibited to a lesser extent by ODQ, only slightly decreased by cPTIO, more markedly inhibited by methemoglobin and N-acetylcysteine, and abolished by acidification before addition to the organ bath. The reaction mixture was found to generate NO as detected by EPR spectroscopy using N-(dithiocarboxy)-N-methyl-D-glucamine (MGD2)-Fe 2+ as spin trap. In conclusion, the Sufide/GSNO reaction products are faster and more pronounced vasorelaxants than GSNO itself. We conclude that in addition to NO formation from SSNO -, reaction products other than polysulfides may give rise to nitroxyl (HNO) and be involved in the pronounced relaxation induced by the Sulfide/GSNO cross-talk.

show abstract

“…Nitric Oxide (NO) is a signaling molecule responsible for several physiological and pathophysiological actions throughout the human body, including blood flow control and modulation of immune res ponse (1,2) . In mammals, NO is considered to circulate as S-nitrosothiols, mainly S-nitrosoglutathione (GSNO), S-nitrosoalbumin and pos sibly S-nitrosohemoglobin (3,4) .…”

Section: Introductionmentioning

confidence: 99%

Assessment of ocular surface toxicity after topical instillation of nitric oxide donors

Cariello¹,

Souza²,

Lowen³

et al. 2013

Arq. Bras. Oftalmol.

View full text Add to dashboard Cite

Ethic committee from UNIFESP: number 1573/08. ABSTRACTPurpose: To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-Nace tylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM. Methods: Ex vivo GSNO and SNAC toxicities were clinically and histologically ana lyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. Results: Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. The re was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as "non-irritating". There was no evidence of tissue toxicity in the histological analysis in all animals. Conclusion: Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.

show abstract

Vascular smooth muscle relaxation mediated by nitric oxide donors: a comparison with acetylcholine, nitric oxide andnitroxyl ion

Cited by 114 publications

References 36 publications

Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta

Gold nanoparticle modifies nitric oxide release and vasodilation in rat aorta

The reaction products of sulfide and S-nitrosoglutathione are potent vasorelaxants

Assessment of ocular surface toxicity after topical instillation of nitric oxide donors

Contact Info

Product

Resources

About