Inhibition of nitrovasodilators by pyocyanin and methylene blue is dissociated from nitric oxide formation

1994 ◽  
Vol 72 (7) ◽  
pp. 746-752 ◽  
Author(s):  
Jovan Bozinovski ◽  
James F. Brien ◽  
Gerald S. Marks ◽  
Kanji Nakatsu
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Sodium Nitroprusside ◽  
Isosorbide Dinitrate ◽  
Rabbit Aorta ◽  
Aortic Ring ◽  
Organic Nitrates ◽  
No Production ◽  
Nitric Oxide Formation ◽  
No Formation

The phenazine pigment pyocyanin (Pyo), like methylene blue (MB), inhibits vascular relaxation induced by organic nitrates. These nitrovasodilators are pro-drugs that have in common the ability to generate nitric oxide (NO). In this study, we characterized responses of rabbit isolated aortic ring to 3-morpholinosydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside, glyceryl trinitrate (GTN), and isosorbide dinitrate in the presence and absence of 10 μM Pyo. We also examined the effect of Pyo (1 and 10 μM) and MB (1 and 10 μM) on vasorelaxation induced by authentic NO, and finally we tested the effects of Pyo and MB on the tissue-independent formation of NO from SIN-1, SNAP, and sodium nitroprusside, using die chemiluminescence – headspace gas method. Pyo (10 μM) surmountably inhibited aortic responses to GTN, isosorbide dinitrate, SIN-1, and SNAP with a characteristic rightward shift of the dose–response curve; the apparent EC50 of these drugs for relaxation of phenylephrine-contracted aorta was increased 18-, 4-, 13-, and 15-fold, respectively. Pyo (1 and 10 μM) and MB (10 μM) inhibited NO-induced vasorelaxation at the EC50 of NO by 35, 72, and 56%. In contrast, Pyo did not inhibit sodium nitroprusside induced vasodilation. For a 10-min incubation, 10 μM Pyo or MB increased NO production from SNAP 1.8- and 2.9-fold, respectively, and increased NO production from SIN-1 by 3.8- and 7.1-fold, respectively. Neither Pyo nor MB enhanced NO formation from sodium nitroprusside. These data indicate that Pyo and MB inhibit nitrovasodilator-induced relaxation of aortic ring by interfering with the action of NO, subsequent to its formation.Key words: pyocyanin, nitric oxide, methylene blue, nitrovasodilators, rabbit aorta.

Protein kinase βII in Zucker obese rats compromises oxygen and flow-mediated regulation of nitric oxide formation

2004 ◽  
Vol 286 (2) ◽  
pp. H492-H497 ◽  
Author(s):  
H. Glenn Bohlen
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Flow Velocity ◽  
Oxygen Depletion ◽  
Oxygen Availability ◽  
Zucker Rats ◽  
No Production ◽  
Nitric Oxide Formation ◽  
No Formation ◽  
Obese Rats

In severe obesity, microvascular endothelial regulation of nitric oxide (NO) formation is compromised in response to muscarinic stimulation, and major arteries have suppressed flow-mediated dilation. Because normal microvessels are highly dependent on flow-mediated stimulation of NO generation and are responsive to intra- and extravascular oxygen availability, they are likely a major site of impaired endothelial regulation. This study evaluated the blood flow and oxygen-dependent aspects of intestinal microvascular regulation and NO production in Zucker obese rats just before the onset of hyperglycemia. Ruboxistaurin (LY-333531) was used to inhibit PKC-βII to determine whether flow or oxygen-related NO regulation was improved. Blood flow velocity was increased by forcing arterioles to perfuse ∼50% larger tissue areas by occlusion of nearby arterioles, and oxygen tension in the bath was lowered to create a modest oxygen depletion. When compared with lean Zucker rats, the periarteriolar NO concentration ([NO]) for obese rats was ∼30% below normal. At elevated shear rates, the [NO] for arterioles of obese animals was 20–30% below those in the arterioles of lean rats, and the NO response to decreased oxygen was about half normal in obese rats. All of these regulatory problems were essentially corrected in obese rats by PKC blockade with only minor changes in the microvascular behavior in lean rats. Therefore, activation of PKC-βII in endothelial cells during obesity suppressed NO regulation both at rest and in response to increased flow velocity and decreased oxygen availability.

Is nitric oxide the only endothelium-derived relaxing factor in canine femoral veins?

1989 ◽  
Vol 257 (6) ◽  
pp. H1910-H1916 ◽  
Author(s):  
V. M. Miller ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Superoxide Dismutase ◽  
Sodium Nitroprusside ◽  
Femoral Vein ◽  
Pulmonary Veins ◽  
Chemical Properties ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583

Nitric oxide may be an endothelium-derived relaxing factor in systemic arteries and pulmonary veins. The endothelium-derived relaxing factor of systemic veins has not been characterized. Experiments were designed to determine whether the endothelium-derived relaxing factor of systemic veins shared chemical properties and mechanisms of action with nitric oxide. Rings of the canine femoral vein with and without endothelium were suspended in organ chambers for the measurement of isometric force. In rings without endothelium, relaxations to nitric oxide were augmented by superoxide dismutase plus catalase and were inhibited by hemoglobin, methylene blue, and LY 83583. The endothelium-dependent relaxations to acetylcholine and A23187 were not augmented by superoxide dismutase plus catalase but were inhibited by hemoglobin and only moderately reduced by either methylene blue or LY 83583. Relaxations to sodium nitroprusside were not inhibited by methylene blue and LY 83583. Relaxations to sodium nitroprusside were inhibited by ouabain and K+-free solution; those to nitric oxide were not. These results indicate that although the endothelium-derived relaxing factor released from canine systemic veins shares some chemical properties with nitric oxide, the mechanism by which relaxations are induced by the two differ. A factor dissimilar to nitric oxide but acting like sodium nitroprusside may be released by the endothelium of canine systemic veins.

scholarly journals Constitutive nitric oxide production by rat alveolar macrophages

1998 ◽  
Vol 274 (3) ◽  
pp. L360-L368 ◽  
Author(s):  
P. R. Miles ◽  
L. Bowman ◽  
A. Rengasamy ◽  
L. Huffman
Keyword(s):  
Nitric Oxide ◽  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Lung Surfactant ◽  
Calcium Ionophore ◽  
Cell Types ◽  
Alveolar Type ◽  
No Production ◽  
No Formation

Results from previous studies suggest that alveolar macrophages must be exposed to inflammatory stimuli to produce nitric oxide (⋅ NO). In this study, we report that naive unstimulated rat alveolar macrophages do produce ⋅ NO and attempt to characterize this process. Western blot analysis demonstrates that the enzyme responsible is an endothelial nitric oxide synthase (eNOS). No brain or inducible NOS can be detected. The rate of ⋅ NO production is ∼0.07 nmol ⋅ 106cells−1 ⋅ h−1, an amount that is less than that produced by the eNOS found in alveolar type II or endothelial cells. Alveolar macrophage ⋅ NO formation is increased in the presence of extracellularl-arginine, incubation medium containing magnesium and no calcium, a calcium ionophore (A-23187), or methacholine. ⋅ NO production is inhibited by N G-nitro-l-arginine methyl ester (l-NAME) but not by N G-nitro-l-arginine,l- N 5-(1-iminomethyl)ornithine hydrochloride, or aminoguanidine. Incubation with ATP, ADP, or histamine also inhibits ⋅ NO formation. Some of these properties are similar to and some are different from properties of eNOS in other cell types. Cellular ⋅ NO levels do not appear to be related to ATP or lactate content. Alveolar macrophage production of ⋅ NO can be increased approximately threefold in the presence of lung surfactant or its major component, dipalmitoyl phosphatidylcholine (DPPC). The DPPC-induced increase in ⋅ NO formation is time and concentration dependent, can be completely inhibited by l-NAME, and does not appear to be related to the degradation of DPPC by alveolar macrophages. These results demonstrate that unstimulated alveolar macrophages produce ⋅ NO via an eNOS and that lung surfactant increases ⋅ NO formation. This latter effect may be important in maintaining an anti-inflammatory state in vivo.

scholarly journals CHICKEN ANAEMIA VIRUS IMPAIRS NITRIC OXIDE PRODUCTION IN HD11 CHICKEN MACROPHAGES

2020 ◽  
Vol 57 (4) ◽  
Author(s):  
Katja Ester ◽  
William Lauman Ragland
Keyword(s):  
Nitric Oxide ◽  
Severe Disease ◽  
Interferon Γ ◽  
Economic Losses ◽  
No Production ◽  
Subclinical Infection ◽  
Chicken Anaemia Virus ◽  
No Formation ◽  
Chicken Macrophage ◽  
Oxide Synthase

Immunosuppressive viruses cause substantial economic losses to the poultry industry. Chicken anaemia virus (CAV) causes severe disease in young chickens, whereas subclinical infection in older birds causes immunosuppression. In this study, we addressed the ability of CAV to interfere with production of antimicrobial molecule nitric oxide (NO) by macrophages. NO production in chicken macrophage cell line HD11 was induced using both Toll-like receptor 4 agonist, bacterial lipopolysaccharide, and an immune modulator, interferon-γ. In addition, we treated macrophages with CAV propagated in chicken lymphoblastoid cells. The levels of NO were measured by the Griess reaction. Addition of CAV decreased both the interferon-γ and the lipopolysaccharide associated induction of NO. Observed effect was not caused by CAV-related cytotoxicity, as no decrease in number of viable cells was observed. Although CAV could not completely abrogate NO production, attenuation of NO induction was clearly present. We have previously shown that CAV interferes with the expression of interferons in chickens during subclinical infection. Since the signalling pathways of expression of interferons and type 2 nitric oxide synthase, enzyme involved in NO formation, overlap, we conclude that measured decrease in NO levels is a consequence of CAV interference with interferon and NO synthase signalling. Regardless of the fact whether the attenuation of NO serves as a viral primary defence, or is only a secondary effect, it could impair the immune response to other pathogens and contribute to the global immunosuppression in chicken houses.Key words: chicken; immunosuppression; chicken anaemia virus (CAV); macrophage; nitric oxide (NO) VIRUS PIŠČANČJE ANEMIJE VPLIVA NA PROIZVODNJO DUŠIKOVIH OKSIDOV V MAKROFAGIH PIŠČANEV HD11 Povzetek: Imunosupresivni virusi povzročajo velike gospodarske izgube v perutninski industriji. Virus piščančje anemije (CAV) pri mladih piščancih povzroča hudo bolezen, medtem ko subklinična okužba pri starejših pticah povzroča oslabljen imunski odziv. V tej raziskavi je bil spremljan vpliv CAV na proizvodnjo dušikovih oksidov (NO) v makrofagih. Proizvodnja NO v piščančjih makrofagih v celični liniji HD11 je bila sprožena z uporabo agonista Toll-u podobnega receptorja 4, bakterijskega lipopolisaharida in imunskega modulatorja interferona-γ, makrofagi pa so bili okuženi s CAV, razmnoženim v piščančjih limfoblastoidnih celicah. Ravni NO so izmerili po Griessovi reakciji. Prisotnost CAV je zmanjšala proizvodnjo NO, spodbujeno tako z interferonom-γ, kot z lipopolisaharidom. Opaženega učinka ni povzročila citotoksičnost, povezana s CAV, saj ni bilo opaziti zmanjšanja števila živih celic. Čeprav CAV ni popolnoma zavrla nastajanja NO, je bilo očitno prisotno zmanjšanje nastajanja NO. Pred tem so pokazali, da CAV moti izražanje interferonov pri piščancih med subklinično okužbo. Ker se poti znotrajceličnega prenosa urejanja izražanja interferonov in sintaze dušikovih oksidov tipa 2, encima, ki sodeluje pri tvorbi NO, prekrivajo, predvidevamo, da je izmerjeno znižanje ravni NO posledica motenj CAV pri znotrajceličnem prenosu sporočila interferona do sintaze dušikovih oksidov. Ne glede na to, ali zaviranje nastajanja NO služi kot primarna virusna obramba ali je le sekundarni učinek, lahko poslabša imunski odziv na druge patogene in prispeva k splošnemu zmanjšanju imunskega odziva v kurnikih ali na kokošjih farmah.Ključne besede: piščanci; zmanjšanje imunskega odziva; virus piščančje anemije (CAV); makrofagi; dušikov oksid (NO)

scholarly journals Effect of MnSOD (E. coli) on the relaxation caused by sodium nitroprusside on isolated rat renal artery

2004 ◽  
Vol 69 (11) ◽  
pp. 973-980 ◽  
Author(s):  
Slobodan Milovanovic ◽  
Zorana Orescanin ◽  
Snezana Spasic ◽  
Srdjan Miletic ◽  
Milica Prostran ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Artery ◽  
Sodium Nitroprusside ◽  
Relaxation Effect ◽  
Renal Arteries ◽  
Nitric Oxide Donor ◽  
No Production ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Relaxation Effects

In this study themolecular foundation of nitric oxide induced relaxation of arteries, with or without endothelium, of normotensive and spontanously hypertensive ratswas re-examined. With this purpose in mind, the effects of the nitric oxide donor sodium nitroprusside (NaNP), with and without manganese containing superoxide dismutase (MnSOD E.C. 1.15.1.1), on rat renal artery relaxation was strudied. The results show that the relaxation effect of NaNP is two times higher in normotensive, compared to spontaneously hypertensive rats. Similar differences exist in the relaxation effects of NaNP on isolated renal arteries without endothelium, indicating that besides the difference in the function of an endothelium, concerning basal NO production in normotensive and hypertensive rats, there is a differencewith respect to NO relaxation in the smoothmuscle that is induced by hypertension. MnSOD decreased the relaxation effect of NaNP in all the examined renal arteries, more in normotensive than in hypertensive ones regardless of the presence of an endothelium. These results show that MnSOD, by modifying the chemical versatility of NO into redox active forms - nitrosonium (NO+) and nitroxyl (NO-), produces different relaxation effects in normotensive and hypertensive arteries of rats, with or without an endothelium, potentiating the role of nitroxyl induced relaxation in sponteneously hypertensive rats. The results prove the need for the synthesis of complex NO donors, as the mechanisms of artery relaxation are different due to an endothel and smooth mouscle changes in hypertensive, as compared to normotensive rats.

scholarly journals Numerical studies of nitric oxide formation in nanosecond-pulsed discharge-stabilized flames of premixed methane/air

2015 ◽  
Vol 373 (2048) ◽  
pp. 20140331
Author(s):  
Moon Soo Bak ◽  
Mark A. Cappelli
Keyword(s):  
Nitric Oxide ◽  
Atomic Oxygen ◽  
Oh Radicals ◽  
Post Discharge ◽  
Nitric Oxide Formation ◽  
No Formation ◽  
Numerical Studies ◽  
Discharge Temperature ◽  
Discharge Simulation ◽  
Kinetics Of

A simulation is developed to investigate the kinetics of nitric oxide (NO) formation in premixed methane/air combustion stabilized by nanosecond-pulsed discharges. The simulation consists of two connected parts. The first part calculates the kinetics within the discharge while considering both plasma/combustion reactions and species diffusion, advection and thermal conduction to the surrounding flow. The second part calculates the kinetics of the overall flow after mixing the discharge flow with the surrounding flow to account for the effect that the discharge has on the overall kinetics. The simulation reveals that the discharge produces a significant amount of atomic oxygen (O) as a result of the high discharge temperature and dissociative quenching of excited state nitrogen by molecular oxygen. This atomic oxygen subsequently produces hydroxyl (OH) radicals. The fractions of these O and OH then undergo Zel’dovich reactions and are found to contribute to as much as 73% of the total NO that is produced. The post-discharge simulation shows that the NO survives within the flow once produced.

scholarly journals Blockade of Retinal NMDA Receptors by Sodium Nitroprusside Is Probably Due to Nitric Oxide Formation

1993 ◽  
Vol 62 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Hisamitsu Ujihara ◽  
Akinori Akaike ◽  
Yutaka Tamura ◽  
Takeharu Yokota ◽  
Masashi Sasa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nmda Receptors ◽  
Sodium Nitroprusside ◽  
Oxide Formation ◽  
Nitric Oxide Formation

Nitric Oxide Detection and Visualization in Biological Systems. Applications of the FNOCT Method

2000 ◽  
Vol 381 (7) ◽  
pp. 575-582 ◽  
Author(s):  
Petra Meineke ◽  
Ursula Rauen ◽  
Herbert de Groot ◽  
Hans-Gert Korth ◽  
Reiner Sustmann
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Single Cells ◽  
High Sensitivity ◽  
Electron System ◽  
No Production ◽  
No Formation ◽  
Extracellular Release ◽  
No Release ◽  
Spermine Nonoate

Abstract Fluorescent Nitric Oxide Cheletropic Traps (FNOCTs) were applied to specifically trap nitric oxide (NO) with high sensitivity. The fluorescent oquinoid ?electron system of the FNOCTs (? = 460 nm, ? = 600 nm) reacts rapidly with NO to a fluorescent phenanthrene system (? = 380 nm, ? = 460 nm). The cyclic nitroxides thus formed react further to nonradical products which exhibit identical fluorescence properties. Using the acid form of the trap (FNOCT-4), NO release by spermine NONOate and by lipopolysaccharide (LPS) activated alveolar macrophages were studied. A maximum extracellular release of NO of 37.5 nmol h[-1] (10[6] cells)[-1] from the macrophages was determined at 11 h after activation. Furthermore, intracellular NO release by LPSactivated macrophages and by microvascular omentum endothelial cells stimulated by the Ca[2+] ionophore A-23187, respectively, was monitored on the single cell level by means of fluorescence microscopy. After loading the cells with the membranepermeating acetoxymethylester derivative FNOCT-5,which is hydrolyzed to a nonpermeating dicarboxylate by intracellular hydrolases, NO formation by the endothelial cells started immediately upon stimulation, whereas start of NO production by the macrophages was delayed with a variation between 4 and 8 h for individual cells. These results demonstrate that the FNOCTs can be used to monitor NO release from single cells, as well as from NOdonating compounds, with high sensitivity and with temporal and spatial resolution.

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