scholarly journals The Nitric Oxide (NO) Donor Sodium Nitroprusside (SNP) and Its Potential for the Schizophrenia Therapy: Lights and Shadows

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3196
Author(s):  
Elli Zoupa ◽  
Nikolaos Pitsikas
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Mental Disease ◽  
No Production ◽  
No Donor ◽  
No Donors ◽  
Worldwide Population ◽  
The Brain

Schizophrenia is a severe psychiatric disorder affecting up to 1% of the worldwide population. Available therapy presents different limits comprising lack of efficiency in attenuating negative symptoms and cognitive deficits, typical features of schizophrenia and severe side effects. There is pressing requirement, therefore, to develop novel neuroleptics with higher efficacy and safety. Nitric oxide (NO), an intra- and inter-cellular messenger in the brain, appears to be implicated in the pathogenesis of schizophrenia. In particular, underproduction of this gaseous molecule is associated to this mental disease. The latter suggests that increment of nitrergic activity might be of utility for the medication of schizophrenia. Based on the above, molecules able to enhance NO production, as are NO donors, might represent a class of compounds candidates. Sodium nitroprusside (SNP) is a NO donor and is proposed as a promising novel compound for the treatment of schizophrenia. In the present review, we intended to critically assess advances in research of SNP for the therapy of schizophrenia and discuss its potential superiority over currently used neuroleptics.

scholarly journals Nitric oxide signalling in plant nanobiology: current status and perspectives

2020 ◽  
Author(s):  
Zsuzsanna Kolbert ◽  
Réka Szőllősi ◽  
Gábor Feigl ◽  
Zoltán Kónya ◽  
Andrea Rónavári
Keyword(s):  
Nitric Oxide ◽  
Basic Research ◽  
Scientific Basis ◽  
Research Field ◽  
Current Status ◽  
Signal Molecules ◽  
No Production ◽  
No Donor ◽  
No Donors ◽  
Agricultural Use

Abstract Plant nanobiology as a novel research field provides a scientific basis for the agricultural use of nanoparticles (NPs). Plants respond to the presence of nanomaterials by synthesizing signal molecules, such as the multifunctional gaseous nitric oxide (NO). Several reports have described the effects of different nanomaterials (primarily chitosan NPs, metal oxide NPs, and carbon nanotubes) on endogenous NO synthesis and signalling in different plant species. Other works have demonstrated the ameliorating effect of exogenous NO donor (primarily sodium nitroprusside) treatments on NP-induced stress. NO-releasing NPs are preferred alternatives to chemical NO donors, and evaluating their effects on plants has recently begun. Previous studies clearly indicate that endogenous NO production in the presence of nanomaterials or NO levels increased by exogenous treatments (NO-releasing NPs or chemical NO donors) exerts growth-promoting and stress-ameliorating effects in plants. Furthermore, an NP-based nanosensor for NO detection in plants has been developed, providing a new and excellent perspective for basic research and also for the evaluation of plants’ health status in agriculture.

The Role of Nitric Oxide in Regulation of Red Blood Cell Deformability.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3730-3730
Author(s):  
Xiaojun He ◽  
Ivan Azarov ◽  
Beth Gordon ◽  
Daniel B. Kim-Shapiro ◽  
Samir K. Ballas
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Flow Channel ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Cell Deformability ◽  
No Donor ◽  
Physiol Heart Circ ◽  
Rbc Deformability

Abstract Nitric Oxide (NO) has been suggested to modulate the deformability of red blood cells (RBCs). Bor-Kucukatay (Bor-Kucukatay et al. Am J Physiol Heart Circ Physiol284: H1577, 2003) found that cells incubated with 1 μM of the NO donor sodium nitroprusside lead to a small but significant increase RBC deformability as measured by ektacytometry. However, no significant effect was seen at lower or higher concentrations of sodium nitroprusside or for any concentration of another NO donor, diethylenetriamine NONOate. Kleinbongard (Kleinbongard et al. Blood10; 3992, 2005) found large increases in red cell deformability as a function of added arginine (the substrate for Nitric Oxide Synthase) by measuring the flow rate through filters. On the other hand, using cell aspiration techniques, Bateman (Bateman et al. Am J Physiol Heart Circ Physiol 280; H2848 H2001) found that NO production during sepsis causes a decrease in RBC deformability. Clearly more work is needed to determine the effects of NO on RBC deformability. The present work was undertaken to further investigate the effect of NO on normal and sickle RBC deformability. ProLi NONOate, arginine, and nitrite (which can be reduced to NO by hemoglobin (Hb), were incubated with blood at various concentrations over a period of 2 hours. Nitrosyl Hb and MetHb formed due to the interaction between NO and RBCs were quantified by electron paramagnetic resonance spectroscopy. The deformability was measured using a flow channel laser diffraction similar to ektacytometry (Huang et al. Am J Hematol67; 151, 2001, Biophys J85; 2374, 2003) with a stress range from 0 to 1,000 Pa. Diffraction patterns produced by deformed cells were analyzed by Matlab®. The deformability coefficients were compared to the control (n=6 per experiment condition). Our results suggested that ProLi NONOate did not significantly effect the deformability of normal RBCs. In a single case, ProLi NONOate improved the deformability of poorly deformable sickle red cells and this result is being studied further. Using our flow channel assay, we did not find any significant affects of arginine on RBC deformability. In addition, our studies involving nitrite, performed under both oxygenated and deoxygenated conditions, suggested that nitrite has no significant effect on RBC deformability. In summary, NO didn’t significantly affect the deformability of normal RBCs, and its potential effects on sickle RBCs needs to be further investigated.

scholarly journals Haem and nitric oxide: synergism in the modulation of the endothelial haem oxygenase-1 pathway

2003 ◽  
Vol 372 (2) ◽  
pp. 381-390 ◽  
Author(s):  
Roberta FORESTI ◽  
Martha HOQUE ◽  
Sandip BAINS ◽  
Colin J. GREEN ◽  
Roberto MOTTERLINI
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Sodium Nitroprusside ◽  
Nitrosative Stress ◽  
No Production ◽  
Oxidative And Nitrosative Stress ◽  
No Donors ◽  
Aortic Endothelial Cells ◽  
Oxygenase Activity ◽  
Haem Oxygenase

NO potently up-regulates vascular haem oxygenase-1 (HO-1), an inducible defensive protein that degrades haem to CO, iron and the antioxidant bilirubin. Since several pathological states are characterized by increased NO production and liberation of haem from haem-containing proteins, we examined how NO influences HO-1 induction mediated by haemin. Aortic endothelial cells treated with S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside (SNP) or diethylenetriamine-NONOate (DETA/NO) and haemin exhibited higher levels of haem oxygenase activity compared with cells exposed to NO donors or haemin alone. This was accompanied by a marked increase in bilirubin production and, notably, by a strong magnification of cellular haem uptake. A role for haem metabolites in modulating HO-1 expression by NO was assessed by exposing cells to SNAP, SNP or DETA/NO in medium derived from cells treated with haemin, which contained increased bilirubin levels. This treatment considerably potentiated HO-1 expression and haem oxygenase activity mediated by NO and the use of a haem oxygenase inhibitor abolished this effect. Both iron liberated during haem breakdown and the formation of nitroxyl anion from NO appeared to partially contribute to the amplifying phenomenon; in addition, medium from haemin-treated cells significantly augmented the release of NO by NO donors. Thus we have identified novel mechanisms related to the induction of HO-1 by NO indicating that the signalling actions of NO vary significantly in the presence of haem and haem metabolites, ultimately increasing the defensive abilities of the endothelium to counteract oxidative and nitrosative stress.

Increase in NADPH-Diaphorase-Positive and Neuronal NO Synthase Immunoreactive Neurons in the Rat Spinal Trigeminal Nucleus Following Infusion of a NO Donor—Evidence for a Feed-Forward Process in NO Production Involved in Trigeminal Nociception

Cephalalgia ◽  
2009 ◽  
Vol 29 (5) ◽  
pp. 566-579 ◽  
Author(s):  
PM Schlechtweg ◽  
J Röder ◽  
MJM Fischer ◽  
W Neuhuber ◽  
K Messlinger
Keyword(s):  
Nitric Oxide ◽  
Afferent Input ◽  
Central Canal ◽  
Nadph Diaphorase ◽  
No Production ◽  
Spinal Trigeminal Nucleus ◽  
Trigeminal Nucleus ◽  
No Donor ◽  
No Donors ◽  
Nos Isoforms

Nitric oxide (NO) donors, which cause delayed headaches in migraineurs, have been shown to activate central trigeminal neurons with meningeal afferent input in animal experiments. Previous reports indicate that this response may be due to up-regulation of NO-producing cells in the trigeminal brainstem. To investigate this phenomenon further, we determined nitric oxide synthase (NOS)-containing neurons in the rat spinal trigeminal nucleus (STN), the projection site of nociceptive trigeminal afferents, following infusion of the NO donor sodium nitroprusside (SNP). Barbiturate anaesthetized rats were infused intravenously with SNP (50 μg/kg) or vehicle for 20 min or 2 h, and after periods of 3–8 h fixed by perfusion. Cryostat sections of the medulla oblongata containing the caudal STN were histochemically processed for detection of nicotineamide adenine dinucleotide phosphate (NADPH)-diaphorase or immunohistochemically stained for NOS isoforms and examined by light and fluorescence microscopy. The number of neurons positive for these markers was determined. Various forms of neurons positive for NADPH-diaphorase or immunoreactive to neuronal NOS (nNOS) were found in superficial and deep laminae of the STN caudalis and around the central canal. Neurons were not immunopositive for endothelial (eNOS) or inducible (iNOS) NOS isoforms. The number of NADPH-diaphorase-positive neurons increased time dependently after SNP infusion by a factor of more than two. Likewise, the number of nNOS-immunopositive neurons was increased after SNP compared with vehicle infusion. Around the central canal the number of NADPH-diaphorase-positive neurons was slightly increased and the number of nNOS+ neurons not changed after SNP treatment. NO donors increase the number of neurons that produce NO in the STN, possibly by induction of nNOS expression. Increased NO production may facilitate neurotransmitter release and promote nociceptive transmission in the STN. This mechanism may explain the delayed increase in neuronal activity and headache after infusion of NO donors.

Effect of nitric oxide and potassium channel agonists and inhibitors on basilar artery diameter

1997 ◽  
Vol 272 (1) ◽  
pp. H256-H262 ◽  
Author(s):  
C. G. Sobey ◽  
F. M. Faraci
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Basilar Artery ◽  
Selective Inhibitor ◽  
No Production ◽  
No Donor ◽  
K Channels ◽  
Cranial Window ◽  
Endogenous Production ◽  
Direct Activator

The first goal of this study was to examine the hypothesis that dilatation of the basilar artery in response to activation of ATP-sensitive K+ channels is mediated by nitric oxide (NO). Diameter of the basilar artery (209 +/- 5 microns, mean +/- SE) was measured using a cranial window in anesthetized rats. Aprikalim (a direct activator of ATP-sensitive K+ channels) dilated the basilar artery under control conditions. Inhibition of endogenous NO production with NG-nitro-L-arginine (L-NNA, 10(-4) M) did not alter responses to aprikalim. The second goal was to determine whether vasodilatation in response to NO is dependent on activation of calcium-activated K+ channels. Tetraethylammonium (TEA, 10(-3) M), an inhibitor of calcium-activated K+ channels, did not affect dilator responses to sodium nitroprusside (an NO donor) under control conditions. Responses to nitroprusside (10(-8) and 10(-7) M) were augmented more than twofold during application of L-NNA. In the presence of L-NNA, the augmented portion of the response to nitroprusside was inhibited by TEA and iberiotoxin (5 x 10(-8) M, a highly selective inhibitor of calcium-activated K+ channels), but it was not inhibited by glibenclamide (10(-6) M), an inhibitor of ATP-sensitive K+ channels. These findings suggest that dilator responses of the basilar artery to an activator of ATP-sensitive potassium channels are not mediated by NO. Calcium-activated K+ channels may not normally contribute to dilator responses of the basilar artery to nitroprusside. The effects of TEA and iberiotoxin suggest that when endogenous production of NO is inhibited, sodium nitroprusside causes the opening of calcium-activated K+ channels, contributing to an augmented vasodilator response.

Hypoxia compared with normoxia alters the effects of nitric oxide in ischemia-reperfusion lung injury

1997 ◽  
Vol 273 (3) ◽  
pp. L504-L512 ◽  
Author(s):  
Y. C. Huang ◽  
P. W. Fisher ◽  
E. Nozik-Grayck ◽  
C. A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Lung Injury ◽  
Average Rate ◽  
Ischemia Reperfusion ◽  
Oxidant Stress ◽  
No Production ◽  
Protective Effects ◽  
Lung Weight ◽  
Edema Formation ◽  
No Donors

Because both the biosynthesis of nitric oxide (NO.) and its metabolic fate are related to molecular O2, we hypothesized that hypoxia would alter the effects of NO. during ischemia-reperfusion (IR) in the lung. In this study, buffer-perfused lungs from rabbits underwent either normoxic IR (AI), in which lungs were ventilated with 21% O2 during ischemia and reperfusion, or hypoxic IR (NI), in which lungs were ventilated with 95% N2 during ischemia followed by reoxygenation with 21% O2. Lung weight gain (WG) and pulmonary artery pressure (Ppa) were monitored continuously, and microvascular pressure (Pmv) was measured after reperfusion to calculate pulmonary vascular resistance. We found that both AI and NI produced acute lung injury, as shown by increased WG and Ppa during reperfusion. In AI, where perfusate PO2 was > 100 mmHg, the administration of the NO. synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) before ischemia worsened WG and Ppa. Pmv also increased, suggesting a hydrostatic mechanism involved in edema formation. The effects of L-NAME could be attenuated by giving L-arginine and exogenous NO. donors before ischemia or before reperfusion. Partial protection was also provided by superoxide dismutase. In contrast, lung injury in NI at perfusate PO2 of 25-30 mmHg was attenuated by L-NAME; this effect could be reversed by L-arginine. Exogenous NO. donors given either before ischemia or before reperfusion, however, did not increase lung injury. NO. production was measured by quantifying the total nitrogen oxides (NOx) accumulating in the perfusate. The average rate of NOx accumulation was greater in AI than in NI. We conclude that hypoxia prevented the protective effects of NO on AI lung injury. The effects of hypoxia may be related to lower NO. production relative to oxidant stress during IR and/or altered metabolic fates of NO.-mediated production of peroxynitrite by hypoxic ischemia.

Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes

1998 ◽  
Vol 274 (1) ◽  
pp. C245-C252 ◽  
Author(s):  
Junsuke Igarashi ◽  
Masashi Nishida ◽  
Shiro Hoshida ◽  
Nobushige Yamashita ◽  
Hiroaki Kosaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiac Myocytes ◽  
Myocardial Injury ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
No Donor ◽  
Oxide Synthase ◽  
Gpx Activity

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined. Interleukin-1β induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS,l-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso- N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2(0.1 mM, 1 h). Inhibition of iNOS with Nω-nitro-l-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

scholarly journals Hydrogen Sulfide Increases Nitric Oxide Production and Subsequent S-Nitrosylation in Endothelial Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ping-Ho Chen ◽  
Yaw-Syan Fu ◽  
Yun-Ming Wang ◽  
Kun-Han Yang ◽  
Danny Ling Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Hydrogen Sulfide ◽  
Protein Kinase ◽  
Fluorescent Probe ◽  
Acid Methyl Ester ◽  
High Specificity ◽  
Protein S ◽  
No Production ◽  
No Donor

Hydrogen sulfide (H2S) and nitric oxide (NO), two endogenous gaseous molecules in endothelial cells, got increased attention with respect to their protective roles in the cardiovascular system. However, the details of the signaling pathways between H2S and NO in endothelia cells remain unclear. In this study, a treatment with NaHS profoundly increased the expression and the activity of endothelial nitric oxide synthase. Elevated gaseous NO levels were observed by a novel and specific fluorescent probe, 5-amino-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid methyl ester (FA-OMe), and quantified by flow cytometry. Further study indicated an increase of upstream regulator for eNOS activation, AMP-activated protein kinase (AMPK), and protein kinase B (Akt). By using a biotin switch, the level of NO-mediated protein S-nitrosylation was also enhanced. However, with the addition of the NO donor, NOC-18, the expressions of cystathionine-γ-lyase, cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase were not changed. The level of H2S was also monitored by a new designed fluorescent probe, 4-nitro-7-thiocyanatobenz-2-oxa-1,3-diazole (NBD-SCN) with high specificity. Therefore, NO did not reciprocally increase the expression of H2S-generating enzymes and the H2S level. The present study provides an integrated insight of cellular responses to H2S and NO from protein expression to gaseous molecule generation, which indicates the upstream role of H2S in modulating NO production and protein S-nitrosylation.

Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats

2007 ◽  
Vol 293 (5) ◽  
pp. L1261-L1270 ◽  
Author(s):  
Louis G. Chicoine ◽  
Michael L. Paffett ◽  
Mark R. Girton ◽  
Matthew J. Metropoulus ◽  
Mandar S. Joshi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Vascular Tone ◽  
Age Groups ◽  
Soluble Guanylyl Cyclase ◽  
No Production ◽  
Sprague Dawley ◽  
No Donor ◽  
Early Postnatal Development ◽  
Old Rats

Nitric oxide (NO) is an important regulator of vasomotor tone in the pulmonary circulation. We tested the hypothesis that the role NO plays in regulating vascular tone changes during early postnatal development. Isolated, perfused lungs from 7- and 14-day-old Sprague-Dawley rats were studied. Baseline total pulmonary vascular resistance (PVR) was not different between age groups. The addition of KCl to the perfusate caused a concentration-dependent increase in PVR that did not differ between age groups. However, the nitric oxide synthase (NOS) inhibitor Nω-nitro-l-arginine augmented the K+-induced increase in PVR in both groups, and the effect was greater in lungs from 14-day-old rats vs. 7-day-old rats. Lung levels of total endothelial, inducible, and neuronal NOS proteins were not different between groups; however, the production rate of exhaled NO was greater in lungs from 14-day-old rats compared with those of 7-day-old rats. Vasodilation to 0.1 μM of the NO donor spermine NONOate was greater in 14-day lungs than in 7-day lungs, and lung levels of both soluble guanylyl cyclase and cGMP were greater at 14 days than at 7 days. Vasodilation to 100 μM of the cGMP analog 8-(4-chlorophenylthio)guanosine-3′,5′-cyclic monophosphate was greater in 7-day lungs than in 14-day lungs. Our results demonstrate that the pulmonary vascular bed depends more on NO production to modulate vascular tone at 14 days than at 7 days of age. The observed differences in NO sensitivity may be due to maturational increases in soluble guanylyl cyclase protein levels.

Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen

2009 ◽  
Vol 106 (4) ◽  
pp. 1234-1242 ◽  
Author(s):  
Ivan T. Demchenko ◽  
Alex Ruehle ◽  
Barry W. Allen ◽  
Richard D. Vann ◽  
Claude A. Piantadosi
Keyword(s):  
Hyperbaric Oxygen ◽  
Positive Function ◽  
Initial Response ◽  
Brain Regions ◽  
No Production ◽  
No Donor ◽  
Mean Values ◽  
Brain Nitric Oxide ◽  
The Brain ◽  
Phosphodiesterase 5

Oxygen is a potent cerebral vasoconstrictor, but excessive exposure to hyperbaric oxygen (HBO2) can reverse this vasoconstriction by stimulating brain nitric oxide (NO) production, which increases cerebral blood flow (CBF)—a predictor of O2 convulsions. We tested the hypothesis that phosphodiesterase (PDE)-5 blockers, specifically sildenafil and tadalafil, increase CBF in HBO2 and accelerate seizure development. To estimate changes in cerebrovascular responses to hyperoxia, CBF was measured by hydrogen clearance in anesthetized rats, either control animals or those pretreated with one of these blockers, with the NO inhibitor Nω-nitro-l-arginine methyl ester (l-NAME), with the NO donor S-nitroso- N-acetylpenicillamine (SNAP), or with a blocker combined with l-NAME. Animals were exposed to 30% O2 at 1 atm absolute (ATA) (“air”) or to 100% O2 at 4 or 6 ATA. EEG spikes indicated central nervous system CNS O2 toxicity. The effects of PDE-5 blockade varied as a positive function of ambient Po2. In air, CBF did not increase significantly, except after pretreatment with SNAP. However, at 6 ATA O2, mean values for CBF increased and values for seizure latency decreased, both significantly; pretreatment with l-NAME abolished these effects. Conscious rats treated with sildenafil before HBO2 were also more susceptible to CNS O2 toxicity, as demonstrated by significantly shortened convulsive latency. Decreases in regional CBF reflect net vasoconstriction in the brain regions studied, since mean arterial pressures remained constant or increased throughout. Thus PDE-5 blockers oppose the protective vasoconstriction that is the initial response to hyperbaric hyperoxia, decreasing the safety of HBO2 by hastening onset of CNS O2 toxicity.

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