scholarly journals Inverse Relationship between Nitric Oxide Synthases and Endothelin-1 Synthesis in Bovine Corpus Luteum: Interactions at the Level of Luteal Endothelial Cell

Endocrinology ◽  
2006 ◽  
Vol 147 (11) ◽  
pp. 5228-5235 ◽  
Author(s):  
Maya Rosiansky-Sultan ◽  
Eyal Klipper ◽  
Katharina Spanel-Borowski ◽  
Rina Meidan
Keyword(s):  
Nitric Oxide ◽  
Corpus Luteum ◽  
Inverse Relationship ◽  
Prostaglandin F2α ◽  
Inos Mrna ◽  
No Production ◽  
Dependent Manner ◽  
No Donor ◽  
Main Site ◽  
Endothelin 1

Endothelin-1 (ET-1) and nitric oxide (NO) play pivotal roles in corpus luteum (CL) function. The present study examined the interplay between NO and ET-1 synthesis in the bovine CL. We found similar inducible and endothelial NO synthase (iNOS and eNOS, respectively) activities in the young CL (d 1–5) expressing the highest levels of both eNOS and iNOS mRNA. These values later declined at mid-cycle (d 8–15) and remained low at later stages (d 16–18). Luteolysis, initiated by prostaglandin F2α analog administration, further reduced NOS mRNA and by 24 h, NOS values dropped to approximately 15% of those at mid-cycle. eNOS protein levels followed a similar pattern to its mRNA. Because endothelial cells (ECs) are the main site for ET-1 and NO production in the CL, we examined the direct effects of the NO donor, NONOate on luteal ECs (LECs). Elevated NO levels markedly decreased ET-1 mRNA, and peptide concentrations in cultured and freshly isolated LECs in a dose-dependent manner. In agreement, NOS inhibitor, NG-nitro-l-arginine methyl ester, stimulated ET-1 mRNA expression in these cells. Interestingly, NO also up-regulated prostaglandin F2α receptors in LECs. These data show that there is an inverse relationship between NOS and ET-1 throughout the CL life span, and imply that this pattern may be the result of their interaction within the resident LECs. NOS are expressed in a physiologically relevant manner: elevated NO at an early luteal stage is likely to play an important role in angiogenesis, whereas reduced levels of NO during luteal regression may facilitate the sustained up-regulation of ET-1 levels during luteolysis.

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 Glucose release as a response to glucagon in rat hepatocyte culture: involvement of NO signaling

2008 ◽  
pp. 569-575
Author(s):  
H Farghali ◽  
J Hodis ◽  
N Kutinová-Canová ◽  
P Potměšil ◽  
E Kmoníčková ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glycogen Synthase ◽  
Inos Mrna ◽  
No Production ◽  
Rat Hepatocyte ◽  
No Donor ◽  
Glucagon Receptor ◽  
Nos Inhibitors ◽  
No Signaling ◽  
Rat Hepatocyte Culture

Glucagon and α-adrenergic-induced glycogenolysis is realized via the agonist/adenylyl cyclase/cAMP/protein kinase signaling pathway or via the activation of phosphorylase kinase by the mobilized calcium that supports the inhibition of glycogen synthase, respectively. The role of nitric oxide (NO) in this process has not been extensively studied. The present work was directed to the question whether NO is produced during glucagon-induced glycogenolysis in rat hepatocyte in a similar way like α-adrenoceptor stimulation. Glycogen-rich hepatocyte cultures were used. NO production (NO2-) was assessed under the influence of glucagon, dibutyryl cyclic AMP (db-cAMP), forskolin, the nitric oxide synthase (NOS) inhibitors Nω-nitro-Larginine methyl ester (L-NAME) and aminoguanidine, and the NO donor S-nitroso-N-acetyl penicillamine (SNAP). Inducible NOS (iNOS) mRNA was examined by reverse transcription-polymerase chain reaction. Glycogenolysis was followed up by estimation of medium glucose levels. The amount of glucose and NO2 - released by glycogen-rich hepatocytes was increased as a result of glucagon, db-cAMP, forskolin and SNAP treatments. iNOS gene expression was upregulated by glucagon. Glycogenolysis that occurs through glucagon receptor stimulation involves NO production downstream of transduction pathways through an isoform of NO synthase. The present and previous studies document possible involvement of NO signaling in glycogenolytic response to glucagon and adrenergic agonists in hepatocytes.

scholarly journals ADMA injures the glomerular filtration barrier: role of nitric oxide and superoxide

2009 ◽  
Vol 296 (6) ◽  
pp. F1386-F1395 ◽  
Author(s):  
Mukut Sharma ◽  
Zongmin Zhou ◽  
Hiroto Miura ◽  
Andreas Papapetropoulos ◽  
Ellen T. McCarthy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glomerular Filtration ◽  
Soluble Guanylyl Cyclase ◽  
Oxidase Inhibitor ◽  
No Production ◽  
Dependent Manner ◽  
Glomerular Filtration Barrier ◽  
No Donor ◽  
Filtration Barrier ◽  
Cgmp Analog

Chronic kidney disease (CKD) is associated with decreased renal nitric oxide (NO) production and increased plasma levels of methylarginines. The naturally occurring guanidino-methylated arginines N-monomethyl-l-arginine (l-NMMA) and asymmetric dimethyl-l-arginine (ADMA) inhibit NO synthase activity. We hypothesized that ADMA and l-NMMA compromise the integrity of the glomerular filtration barrier via NO depletion. We studied the effect of ADMA on albumin permeability (Palb) in isolated glomeruli and examined whether this effect involves NO- and superoxide (O2•−)-dependent mechanisms. ADMA at concentrations found in circulation of patients with CKD decreased cGMP and increased Palb in a dose-dependent manner. A similar increase in Palb was caused by l-NMMA but at a concentration two orders of magnitude higher than that of ADMA. NO donor DETA-NONOate or cGMP analog abrogated the effect of ADMA on Palb. The SOD mimetic tempol or the NAD(P)H oxidase inhibitor apocynin also prevented the ADMA-induced increase in Palb. The NO-independent soluble guanylyl cyclase (sGC) activator BAY 41–2272, at concentrations that increased glomerular cGMP production, attenuated the ADMA-induced increase in Palb. Furthermore, sGC incapacitation by the heme site-selective inhibitor ODQ increased Palb. We conclude that ADMA compromises the integrity of the filtration barrier by altering the bioavailability of NO and O2•− and that NO-independent activation of sGC preserves the integrity of this barrier under conditions of NO depletion. NO-independent activation of sGS may be a useful pharmacotherapeutic approach for preservation of glomerular function in CKD thereby reducing the risk for cardiovascular events.

Evidence suggesting that nitric oxide mediates iron-induced toxicity in cultured proximal tubule cells

1998 ◽  
Vol 274 (1) ◽  
pp. F18-F25 ◽  
Author(s):  
Liguang Chen ◽  
Bao-Hong Zhang ◽  
David C. H. Harris
Keyword(s):  
Nitric Oxide ◽  
Lipid Peroxidation ◽  
Proximal Tubule ◽  
Cell Damage ◽  
No Production ◽  
Dependent Manner ◽  
No Donor ◽  
Variable Effect ◽  
Proximal Tubule Cells ◽  
Tubule Cells

The potential role of nitric oxide (NO) in iron-induced toxicity was studied in proximal tubule cells in primary culture. NO production ([Formula: see text]/[Formula: see text]) was significantly increased in iron-treated compared with control cells (3.43 ± 0.08 vs. 1.56 ± 0.08 nmol/dish, P < 0.01). NO synthase (NOS) activity was also induced by iron treatment (16.2 ± 2.0 vs. 0.4 ± 0.2 nmol of [Formula: see text]citrulline/mg protein, P < 0.01).l-Arginine, a substrate for NOS, augmented iron-induced NO production and cell damage [lactate dehydrogenase (LDH) leakage], whereas aminoguanidine, an inhibitor of NOS, reduced iron-induced NO production and LDH leakage. Sodium nitroprusside, an exogenous NO donor, induced LDH leakage in a dose-dependent manner, but no effect on lipid peroxidation {malondialdehyde bis[dimethyl acetal] (MDA) production} was observed. Superoxide dismutase and catalase decreased iron-induced MDA production but did not affect LDH leakage or NO production. Dimethylpyrroline N-oxide and desferal prevented MDA production, LDH leakage, and NO production. We concluded that NO is one of the mediators of iron-induced toxicity in proximal tubule cells. NO-induced toxicity is not dependent on lipid peroxidation. This may explain the variable effect of different antioxidants on cell damage and lipid peroxidation in iron-induced cytotoxicity.

scholarly journals Nitric Oxide is Produced by Cowdria ruminantium-Infected Bovine Pulmonary Endothelial Cells In Vitro and Is Stimulated by Gamma Interferon

1998 ◽  
Vol 66 (5) ◽  
pp. 2115-2121 ◽  
Author(s):  
Mbithe Mutunga ◽  
Patricia M. Preston ◽  
Keith J. Sumption
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
No Synthase ◽  
No Production ◽  
Dependent Manner ◽  
Donor Molecule ◽  
No Donor ◽  
Pulmonary Endothelial Cells ◽  
Cowdria Ruminantium ◽  
Dose Dependent

ABSTRACT Nitric oxide (NO) is a labile inorganic free radical produced by NO synthase from the substrate l-arginine in various cells and tissues including endothelial cells. A substantial elevation of nitrite levels indicative of NO production occurred in cultures ofCowdria ruminantium-infected bovine pulmonary endothelial cells (BPEC) incubated in medium alone. Exposure of the infected cultures to recombinant bovine gamma interferon (BorIFN-γ) resulted in more rapid production of NO, reduced viability of C. ruminantium, and induction of endothelial cell death. Significant inhibition of NO production was noted after addition of the NO synthase inhibitor N-monomethyl-l-arginine (l-NMMA), indicating that the increase in production occurred via the inducible NO synthase pathway. Reduction in the infectivity of C. ruminantium elementary bodies (EBs) occurred in a dose-dependent manner after incubation with the NO donor moleculeS-nitroso-N-acetyl-dl-penicillamine (SNAP) prior to infection of endothelial cells. The level of infection in cultures maintained in SNAP was reduced in a dose-dependent manner with significant negative correlation between the final level of infection on day 7 and the level of SNAP (r = −0.96). It was established that pretreatment and cultivation of C. ruminantium EBs with the NO donor molecule SNAP reduced infectivity to cultures and viability of EBs with the implication that release of NO in vivo following infection of endothelial cells may have an effect upon the multiplication of the agent in the host animal and may be involved in the pathogenesis of heartwater through the effect of this molecule upon circulation.

AVP inhibits LPS- and IL-1β-stimulated NO and cGMP via V1 receptor in cultured rat mesangial cells

1999 ◽  
Vol 276 (3) ◽  
pp. F433-F441 ◽  
Author(s):  
Tetsuo Umino ◽  
Eiji Kusano ◽  
Shigeaki Muto ◽  
Tetsu Akimoto ◽  
Satoru Yanagiba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mesangial Cells ◽  
Nuclear Factor Κb ◽  
Inos Mrna ◽  
No Production ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Inos Protein ◽  
Nitrite Production ◽  
Inhibitor Of Protein Synthesis

The present study examined how arginine vasopressin (AVP) affects nitric oxide (NO) metabolism in cultured rat glomerular mesangial cells (GMC). GMC were incubated with test agents and nitrite, and intracellular cGMP content, inducible nitric oxide synthase (iNOS) mRNA, and iNOS protein were analyzed by the Griess method, enzyme immunoassay, and Northern and Western blotting, respectively. AVP inhibited lipopolysaccharide (LPS)- and interleukin-1β (IL-1β)-induced nitrite production in a dose- and time-dependent manner, with concomitant changes in cGMP content, iNOS mRNA, and iNOS protein. This inhibition by AVP was reversed by V1- but not by oxytocin-receptor antagonist. Inhibition by AVP was also reproduced on LPS and interferon-γ (IFN-γ). Protein kinase C (PKC) inhibitors reversed AVP inhibition, whereas PKC activator inhibited nitrite production. Although dexamethasone and pyrrolidinedithiocarbamate (PDTC), inhibitors of nuclear factor-κB, inhibited nitrite production, further inhibition by AVP was not observed. AVP did not show further inhibition of nitrite production with actinomycin D, an inhibitor of transcription, or cycloheximide, an inhibitor of protein synthesis. In conclusion, AVP inhibits LPS- and IL-1β-induced NO production through a V1 receptor. The inhibitory action of AVP involves both the activation of PKC and the transcription of iNOS mRNA in cultured rat GMC.

Pulmonary surfactant inhibits LPS-induced nitric oxide production by alveolar macrophages

1999 ◽  
Vol 276 (1) ◽  
pp. L186-L196 ◽  
Author(s):  
P. R. Miles ◽  
L. Bowman ◽  
K. M. K. Rao ◽  
J. E. Baatz ◽  
L. Huffman
Keyword(s):  
Nitric Oxide ◽  
Alveolar Macrophages ◽  
Pulmonary Surfactant ◽  
Radical Scavenger ◽  
Inos Mrna ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Inos Protein ◽  
No Formation

The objectives of this investigation were 1) to report that pulmonary surfactant inhibits lipopolysaccharide (LPS)-induced nitric oxide (⋅ NO) production by rat alveolar macrophages, 2) to study possible mechanisms for this effect, and 3) to determine which surfactant component(s) is responsible. ⋅ NO produced by the cells in response to LPS is due to an inducible ⋅ NO synthase (iNOS). Surfactant inhibits LPS-induced ⋅ NO formation in a concentration-dependent manner; ⋅ NO production is inhibited by ∼50 and ∼75% at surfactant levels of 100 and 200 μg phospholipid/ml, respectively. The inhibition is not due to surfactant interference with the interaction of LPS with the cells or to disruption of the formation of iNOS mRNA. Also, surfactant does not seem to reduce ⋅ NO formation by directly affecting iNOS activity or by acting as an antioxidant or radical scavenger. However, in the presence of surfactant, there is an ∼80% reduction in the amount of LPS-induced iNOS protein in the cells. LPS-induced ⋅ NO production is inhibited by Survanta, a surfactant preparation used in replacement therapy, as well as by natural surfactant. ⋅ NO formation is not affected by the major lipid components of surfactant or by two surfactant-associated proteins, surfactant protein (SP) A or SP-C. However, the hydrophobic SP-B inhibits ⋅ NO formation in a concentration-dependent manner; ⋅ NO production is inhibited by ∼50 and ∼90% at SP-B levels of 1–2 and 10 μg/ml, respectively. These results show that lung surfactant inhibits LPS-induced ⋅ NO production by alveolar macrophages, that the effect is due to a reduction in iNOS protein levels, and that the surfactant component responsible for the reduction is SP-B.

Expression, localization, and regulation of NOS in human mast cell lines: effects on leukotriene production

Blood ◽  
2004 ◽  
Vol 104 (2) ◽  
pp. 462-469 ◽  
Author(s):  
Mark Gilchrist ◽  
Scott D. McCauley ◽  
A. Dean Befus
Keyword(s):  
Nitric Oxide ◽  
Protein Localization ◽  
Human Mast Cell ◽  
No Production ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
No Donor ◽  
No Formation ◽  
Health And Disease ◽  
Oxide Synthase

Abstract Nitric oxide (NO) is a potent radical produced by nitric oxide synthase (NOS) and has pleiotrophic activities in health and disease. As mast cells (MCs) play a central role in both homeostasis and pathology, we investigated NOS expression and NO production in human MC populations. Endothelial NOS (eNOS) was ubiquitously expressed in both human MC lines and skin-derived MCs, while neuronal NOS (nNOS) was variably expressed in the MC populations studied. The inducible (iNOS) isoform was not detected in human MCs. Both growth factor-independent (HMC-1) and -dependent (LAD 2) MC lines showed predominant nuclear eNOS protein localization, with weaker cytoplasmic expression. nNOS showed exclusive cytoplasmic localization in HMC-1. Activation with Ca2+ ionophore (A23187) or IgE-anti-IgE induced eNOS phosphorylation and translocation to the nucleus and nuclear and cytoplasmic NO formation. eNOS colocalizes with the leukotriene (LT)-initiating enzyme 5-lipoxygenase (5-LO) in the MC nucleus. The NO donor, S-nitrosoglutathione (SNOG), inhibited, whereas the NOS inhibitor, NG-nitro-l-arginine methyl ester (L-NAME), potentiated LT release in a dose-dependent manner. Thus, human MC lines produce NO in both cytoplasmic and nuclear compartments, and endogenously produced NO can regulate LT production by MCs. (Blood. 2004;104: 462-469)

scholarly journals JAK Inhibitors AG-490 and WHI-P154 Decrease IFN-γ-Induced iNOS Expression and NO Production in Macrophages

2006 ◽  
Vol 2006 ◽  
pp. 1-7 ◽  
Author(s):  
Outi Sareila ◽  
Riku Korhonen ◽  
Outi Kärpänniemi ◽  
Riina Nieminen ◽  
Hannu Kankaanranta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inos Expression ◽  
Janus Kinase ◽  
Inos Mrna ◽  
No Production ◽  
Dependent Manner ◽  
Jak Inhibitors ◽  
Concentration Dependent Manner ◽  
Inflammatory Processes ◽  
Nuclear Levels

In inflammation, inducible nitric oxide synthase (iNOS) produces nitric oxide (NO), which modulates inflammatory processes. We investigated the effects of Janus kinase (JAK) inhibitors, AG-490 and WHI-P154, on iNOS expression and NO production in J774 murine macrophages stimulated with interferon-γ(IFN-γ). JAK inhibitors AG-490 and WHI-P154 decreased IFN-γ-induced nuclear levels of signal transducer and activator of transcription 1α(STAT1α). JAK inhibitors AG-490 and WHI-P154 decreased also iNOS protein and mRNA expression and NO production in a concentration-dependent manner. Neither of the JAK inhibitors affected the decay of iNOS mRNA when determined by actinomycin D assay. Our results suggest that the inhibition of JAK-STAT1-pathway by AG-490 or WHI-P154 leads to the attenuation of iNOS expression and NO production in IFN-γ-stimulated macrophages.

Abstract 2305: Endothelin-1 Alters Nitric Oxide-Dependent Cerebrovascular Responses by Modulating The Phosphorylation State of eNOS via Rho Kinase

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Giuseppe Faraco ◽  
Joseph Anrather ◽  
Costantino Iadecola
Keyword(s):  
Nitric Oxide ◽  
Rho Kinase ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Rock Inhibitor ◽  
No Donor ◽  
Doppler Flowmetry ◽  
Phosphorylation State ◽  
Endothelin 1 ◽  
Cranial Window

Hypertension (HTN) alters vital homeostatic mechanisms regulating cerebral blood flow (CBF) and increases the risk of stroke and dementia. HTN exerts some of its damaging effects by counteracting the beneficial vascular actions of nitric oxide (NO). The potent vasoconstrictor endothelin-1 (ET1) has been implicated in the pathogenesis of HTN, but its role in the cerebrovascular effects of HTN is unknown. We examined whether ET1 disrupts CBF regulation. CBF (laser-Doppler flowmetry) was assessed in the somatosensory cortex in anesthetized male C57Bl/6 mice (n=5/group) equipped with a cranial window. ET1 (35 pmol/kg/min; i.v. for 45 min) increased mean arterial pressure from 72±4 to 99±6 mmHg (p<0.05), without reducing resting CBF (p>0.05). However, ET1 attenuated the CBF increase produced by neocortical application of the endothelium-dependent vasodilator acetylcholine (ACh; -37±1%; p<0.05) and by whisker stimulation (-31±1%; p<0.05), responses dependent on NO. The CBF response to adenosine was intact (p>0.05) indicating that ET1 did not act by compromising smooth muscle relaxation. The effects of ET1 were prevented by the ET type A (ET A ) receptor antagonist BQ123 (1µM; p<0.05), by the Rho kinase (ROCK) inhibitor Y27632 (1 µM; p<0.05), but not by the ET B antagonist BQ788 (100nM; p>0.05). ET-1 did not affect the CBF increase produced by the NO donor SNAP and did not increase free radicals, suggesting that ET-1 did not act by reducing NO vasoactivity or bioavailability. However, in brain endothelial cell cultures ET1 (10-100nM) attenuated the NO production induced by ACh (-49±4% at 50nM; p<0.05), an effect blocked by BQ123 and Y27632. ET1 increased eNOS phosphorylation at Thr495, which inhibits eNOS, and reduced phosphorylation at Ser1177, which activates eNOS, effects blocked by Y27632. These findings, collectively, suggest that ET1 alters key regulatory mechanisms of the cerebral circulation by modulating the phosphorylation state of eNOS via ROCK. The resulting downregulation of eNOS activity is responsible for the neurovascular dysregulation induced by ET1. ET A receptors may be a valuable target to counteract the deleterious cerebrovascular actions of HTN.

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