NO Donor (no + donor)

Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by NO Donor

  • no donor sodium nitroprusside

  • Selected Abstracts


    Sydnonimines as Exogenous NO Donors

    CHEMINFORM, Issue 46 2005
    E. Yu.
    Abstract For Abstract see ChemInform Abstract in Full Text. [source]


    ChemInform Abstract: N-Hydroxyl Derivatives of Guanidine Based Drugs as Enzymatic NO Donors.

    CHEMINFORM, Issue 52 2001
    Ming Xian
    Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]


    The nitric oxide/cyclic guanosine monophosphate pathway modulates the inspiratory-related activity of hypoglossal motoneurons in the adult rat

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2008
    Fernando Montero
    Abstract Motoneurons integrate interneuronal activity into commands for skeletal muscle contraction and relaxation to perform motor actions. Hypoglossal motoneurons (HMNs) are involved in essential motor functions such as breathing, mastication, swallowing and phonation. We have investigated the role of the gaseous molecule nitric oxide (NO) in the regulation of the inspiratory-related activity of HMNs in order to further understand how neural activity is transformed into motor activity. In adult rats, we observed nitrergic fibers and bouton-like structures in close proximity to motoneurons, which normally lack the molecular machinery to synthesize NO. In addition, immunohistochemistry studies demonstrated that perfusion of animals with a NO donor resulted in an increase in the levels of cyclic guanosine monophosphate (cGMP) in motoneurons, which express the soluble guanylyl cyclase (sGC) in the hypoglossal nucleus. Modulators of the NO/cGMP pathway were micro-iontophoretically applied while performing single-unit extracellular recordings in the adult decerebrated rat. Application of a NO synthase inhibitor or a sGC inhibitor induced a statistically significant reduction in the inspiratory-related activity of HMNs. However, excitatory effects were observed by ejection of a NO donor or a cell-permeable analogue of cGMP. In slice preparations, application to the bath of a NO donor evoked membrane depolarization and a decrease in rheobase, which were prevented by co-addition to the bath of a sGC inhibitor. These effects were not prevented by reduction of the spontaneous synaptic activity. We conclude that NO from afferent fibers anterogradely modulates the inspiratory-related activity of HMNs by a cGMP-dependent mechanism in physiological conditions. [source]


    Aerobic exercise acutely improves insulin- and insulin-like growth factor-1-mediated vasorelaxation in hypertensive rats

    EXPERIMENTAL PHYSIOLOGY, Issue 5 2010
    Ai-Lun Yang
    Limited information is available concerning the effects of aerobic exercise on vasorelaxation in hypertension. The aim of this study was to investigate the effects of a single bout of aerobic exercise on insulin- and insulin-like growth factor-1 (IGF-1)-induced vasorelaxation in hypertensive rats. Four-month-old spontaneously hypertensive rats were randomly divided into a sedentary group (SHR) and an exercise group (SHR+Ex) subjected to a single bout of aerobic exercise conducted by treadmill running at 21 m min,1 for 1 h. Age-matched Wistar,Kyoto rats were used as a normotensive control group (WKY). Insulin- and IGF-1-induced vasorelaxant responses in the three groups were evaluated by using isolated aortic rings, with or without endothelial denudation, in organ baths. Possible roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS) involved in the NO-dependent vasorelaxation were examined by adding selective inhibitors. The role of superoxide was also clarified by adding superoxide dismutase (SOD). In addition, the endothelium-independent vascular responses to sodium nitroprusside (SNP), a NO donor, were examined. The insulin- and IGF-1-induced vasorelaxation was significantly (P < 0.05) decreased in the SHR group compared with the WKY group. This decreased response in SHR was improved by exercise. These vasorelaxant responses among the three groups became similar after endothelial denudation and pretreatment with the PI3K inhibitor, NOS inhibitor or SOD. Also, no difference among groups was found in the SNP-induced vasorelaxation. We concluded that a single bout of aerobic exercise acutely improves insulin- and IGF-1-mediated vasorelaxation in an endothelium-dependent manner in hypertensive rats. [source]


    Central nitric oxide blocks vasopressin, oxytocin and atrial natriuretic peptide release and antidiuretic and natriuretic responses induced by central angiotensin II in conscious rats

    EXPERIMENTAL PHYSIOLOGY, Issue 5 2007
    Wagner Luis Reis
    The presence of nitric oxide synthase (NOS), the enzyme that catalyses the formation of nitric oxide (NO), in the circumventricular organs and magnocellular neurones suggests an important role of NO in the modulation of vasopressin (AVP) and oxytocin (OT) release. Intracerebroventricular (i.c.v.) injection of angiotensin II (Ang II) stimulates the release of AVP, OT and atrial natriuretic peptide (ANP), with the resultant antidiuretic and natriuretic effects. This study investigated the interaction between nitrergic and angiotensinergic pathways on the release of AVP, OT and ANP and on urinary volume and sodium excretion in water-loaded rats. Unanaesthetized, freely moving, male Wistar rats received two water loads followed by an injection into the lateral ventricle of an inhibitor of NOS (l -NAME), a NO donor [3-morpholinylsydnoneimine chloride (SIN-1) or S -nitroso- N -acetyl penicillamine (SNAP)] or vehicle (isotonic saline) and, 20 min after, they received a second i.c.v. injection of Ang II or vehicle. Injections of l -NAME or Ang II produced an increase in plasma levels of AVP, OT and ANP, a reduction in urinary volume and an increase in sodium excretion. Pretreatment with l -NAME enhanced the Ang II-induced increase in AVP, OT and ANP release, as well as the antidiuresis and natriuresis. Injection of SIN-1 or SNAP did not modify hormonal plasma levels and urinary parameters. In contrast SNAP blocked the AVP, OT and ANP release, as well as antidiuretic and natriuretic responses induced by ANG-II. Thus, the central nitrergic system can act to inhibit AVP, OT and ANP secretion and the antidiuretic and natriuretic effects in response to Ang II. [source]


    Differential regulation of the nitric oxide,cGMP pathway exacerbates postischaemic heart injury in stroke-prone hypertensive rats

    EXPERIMENTAL PHYSIOLOGY, Issue 1 2007
    Tetsuji Itoh
    Using a working perfused heart model, we investigated the hypothesis that alterations in the NO,cGMP pathway may exacerbate postischaemic mechanical dysfunction in the hypertrophied heart. Ischaemia for 25 min followed by reperfusion for 30 min produced marked cardiac mechanical dysfunction in both stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY). Exogenous treatment with S -nitroso- N -acetyl- dl -penicillamine (SNAP), a NO donor, had beneficial effects on the cardiac dysfunction induced by ischaemia,reperfusion (I/R) in the WKY heart, but the cardioprotective effect of SNAP was eliminated by guanylyl cyclase inhibitor. Cardiac cGMP levels were increased by SNAP or ischaemia in WKY. In contrast, in SHRSP hearts, SNAP could not alleviate the cardiac dysfunction caused by I/R. Pre-ischaemia, the cardiac cGMP level was significantly higher in SHRSP than in WKY; however, no significant difference was found after SNAP and ischaemia. The myocardial Ca2+ -dependent NO synthase (NOS) activity increased at the end of ischaemia in WKY. Conversely, the Ca2+ -independent NOS activity and protein levels were upregulated by I/R in the SHRSP myocardium. In the SHRSP hearts, non-selective NOS and selective Ca2+ -independent NOS inhibitors or antioxidant treatment alleviated cardiac dysfunction caused by I/R. Moreover, mRNA expression and Western blotting analysis of cGMP-dependent protein kinase type I showed more deterioration of SHRSP hearts compared with WKY. These results suggest that: (1) the NO-dependent cardioprotective effect is depressed; and (2) overproduction of NO derived from Ca2+ -independent NOS contributes to postischaemic heart injury in the hypertrophied heart of hypertensive status. [source]


    Nuclear factor-kappaB as a molecular target for migraine therapy.

    HEADACHE, Issue 4 2003
    U Reuter
    Ann Neurol. 2002;51:507-516. Nitric oxide (NO) generated from inducible NO synthase (iNOS) participates in immune and inflammatory responses in many tissues. The NO donor glyceryl trinitrate (GTN) provokes delayed migraine attacks when infused into migraineurs and also causes iNOS expression and delayed inflammation within rodent dura mater. Sodium nitroprusside, an NO donor as well, also increases iNOS expression. Because inflammation and iNOS are potential therapeutic targets, we examined transcriptional regulation of iNOS following GTN infusion and the consequences of its inhibition within dura mater. We show that intravenous GTN increases NO production within macrophages. L-N(6)-(1-iminoethyl)lysine, a selective iNOS inhibitor, attenuates the NO signal, emphasizing the importance of enzymatic activity to delayed NO production. iNOS expression is preceded by significant nuclear factor kappa B (NF-kappaB) activity, as reflected by a reduction in the inhibitory protein-kappa-Balpha (IkappaBalpha) and activation of NF-kappaB after GTN infusion. IkappaBalpha degradation, NF-kappaB activation, and iNOS expression were attenuated by parthenolide (3mg/kg), the active constituent of feverfew, an anti-inflammatory drug used for migraine treatment. These findings suggest that GTN promotes NF-kappaB activity and inflammation with a time course consistent with migraine attacks in susceptible individuals. We conclude, based on results with this animal model, that blockade of NF-kappaB activity provides a novel transcriptional target for the development of anti-migraine drugs. Comment: This paper suggesting the localization of NO production in dural macrophages as part of delayed inflammation may indicate proliferation and or recruitment of these cells in migraine. Could this also be a target for drug treatment? Specifically, is the genetic transcription that leads to nitric oxide generation such a target? To amend slightly the old advertising slogan, "when Michael Moskowitz talks, we all listen." DSM and SJT [source]


    Decreased hepatic nitric oxide production contributes to the development of rat sinusoidal obstruction syndrome

    HEPATOLOGY, Issue 4 2003
    Laurie D. Deleve M.D., Ph.D.
    This study examined the role of decreased nitric oxide (NO) in the microcirculatory obstruction of hepatic sinusoidal obstruction syndrome (SOS). SOS was induced in rats with monocrotaline. Monocrotaline caused hepatic vein NO to decrease by 30% at 24 hours and by 70% at 72 hours; this decrease persisted throughout late SOS. NG -nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, exacerbated monocrotaline toxicity, whereas V-PYRRO/NO, a liver-selective NO donor prodrug, restored NO levels, preserved sinusoidal endothelial cell (SEC) integrity and sinusoidal perfusion as assessed by in vivo microscopy and electron microscopy, and prevented clinical and histologic evidence of SOS. NO production in vitro by SEC and Kupffer cells, the 2 major liver cell sources of NO, decreases largely in parallel with loss of cell viability after exposure to monocrotaline. Increased matrix metalloproteinase (MMP) activity increases early on in SOS and this increase in activity has been implicated in initiating SOS. Infusion of V-PYRRO-NO prevented the monocrotaline-induced increase in MMP-9. In conclusion, decreased hepatic NO production contributes to the development of SOS. Infusion of an NO donor preserves SEC integrity and prevents development of SOS. These findings show that a decrease in NO contributes to SOS by allowing up-regulation of MMP activity, loss of sinusoidal integrity, and subsequent disruption of sinusoidal perfusion. (Hepatology 2003;38:900,908). [source]


    Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosis

    HEPATOLOGY, Issue 2 2003
    Lia Bellis
    Postprandial hyperemia is associated with a significant increase in portal pressure in cirrhosis, which may contribute to progressive dilation and rupture of gastroesophageal varices. In cirrhosis, an insufficient hepatic production of nitric oxide (NO) may impair the expected hepatic vasodilatory response to increased blood flow, further exaggerating the postprandial increase in portal pressure. This study was aimed at investigating whether low doses of an oral NO donor might counteract the postprandial peak in portal pressure. Twenty-three portal hypertensive cirrhotics, 8 of them under propranolol therapy, were randomized to receive orally 5-isosorbide mononitrate (ISMN; 10 mg; n = 11) or placebo (n = 12) and a standard liquid meal 15 minutes later. Hepatic venous pressure gradient (HVPG), mean arterial pressure (MAP), and hepatic blood flow (HBF) were measured at baseline and 15, 30, and 45 minutes after a meal. ISMN significantly attenuated the postprandial increase in portal pressure as compared with placebo (peak HVPG increase: 2.4 1.4 mm Hg vs. 5.2 2.1 mm Hg, P = .002). Percentual increases in HBF were similar in both groups. MAP decreased slightly in ISMN group (,7.5% .5%; P < .01 vs. baseline). These effects were also observed in patients on chronic propranolol therapy. In conclusion, hepatic NO supplementation by low doses of ISMN effectively reduces the postprandial increase of portal pressure in cirrhosis, with only a mild effect on arterial pressure. The same was observed in patients receiving propranolol. Our results suggest that therapeutic strategies based on selective hepatic NO delivery may improve the treatment of portal hypertension. [source]


    Inhibition of heme oxygenase-1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice

    INTERNATIONAL JOURNAL OF CANCER, Issue 3 2007
    Kaeko Hirai
    Abstract Heme oxygenase (HO)-1 is a key player reducing cytotoxicity and enhancing protumoral effects of nitric oxide (NO). We examined zinc protoporphyrin (ZnPP) IX, an HO-1 inhibitor, to affect tumor growth of LL/2 mouse lung cancer cells. ZnPPIX reduced HO-1 expression and HO activity in LL/2 cells, whereas cobalt PPIX (CoPPIX), an HO-1 activator, increased both. LL/2 cells treated with sodium nitropurusside, an NO donor, showed growth inhibition dose-dependently, which was enhanced by ZnPPIX cotreatment, but was reduced by CoPPIX. In mice tumors, ZnPPIX decreased HO-1 expression. LL/2-tumors were found in 88% (7/8) vehicle-treated mice, whereas tumors were found in 38% (3/8) and 25% (2/8) mice treated with 5 and 20 ,g/mouse ZnPPIX, respectively (p = 0.0302). Tumor growth was inhibited dose-dependently by ZnPPIX. Vascular endothealial growth factor concentration in tumors was reduced by ZnPPIX (p = 0.0341). Microvessel density (MVD) in ZnPPIX-treated tumors was lower than that in vehicle-treated tumors (p = 0.0362). Apoptotic cell count in ZnPPIX-treated tumors was higher than that in vehicle-treated tumors (p = 0.0003). In contrast, CoPPIX treatment increased HO-1 expression, enhanced tumorigenicity and MVD and reduced apoptosis. From these findings, inhibition of HO-1 by ZnPPIX provides relevant antitumoral effects. 2006 Wiley-Liss, Inc. [source]


    The effect of nitric oxide on cyclooxygenase-2 (COX-2) overexpression in head and neck cancer cell lines

    INTERNATIONAL JOURNAL OF CANCER, Issue 5 2003
    Seok-Woo Park
    Abstract The overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) has been previously reported in head and neck squamous cell carcinoma (HNSCC), as well as in many cancers. We hypothesized that endogenous nitric oxide (NO) might increase the expression of COX-2 in cancer cells. Therefore, we investigated the cross-talk between NO and the prostaglandin (PG) pathways in HNSCC cell lines. We found that COX-2 and iNOS expressions were elevated simultaneously. On adding the NO donor, SNAP, the PGE2 level was increased 2,20 times due to increased COX-2 expression. This increase of COX-2 expression by SNAP or PMA (potent inducer of both iNOS and COX-2) was blocked to various degrees by NO scavengers and NOS inhibitors (L-NAME and 1400W). Also, the expression of COX-2 in resting cells was inhibited by NOS inhibitors. Moreover, COX-2 expression, induced by SNAP, was inhibited by ODQ, a soluble guanylate cyclase (sGC) inhibitor. The effect of dibutyryl-cGMP on COX-2 expression was similar to that of SNAP. These results imply that endogenous or exogenous NO activates sGC and that the resulting increase of cGMP induces a signaling that upregulates the expression of COX-2 in HNSCC cell lines. We also observed that NO increased COX-2 expression in different cancer cell lines, including cervic and gastric cancer cell lines. These findings further support the notion that NO can be associated with carcinogenesis through the upregulation of COX-2, and that NOS inhibitor may be also useful for cancer prevention. 2003 Wiley-Liss, Inc. [source]


    DROUGHT STRESS: Comparative Time Course Action of the Foliar Applied Glycinebetaine, Salicylic Acid, Nitrous Oxide, Brassinosteroids and Spermine in Improving Drought Resistance of Rice

    JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 5 2010
    M. Farooq
    Abstract Worldwide rice productivity is being threatened by increased endeavours of drought stress. Among the visible symptoms of drought stress, hampered water relations and disrupted cellular membrane functions are the most important. Exogenous use of polyamines (PAs), salicylic acid (SA), brassinosteroids (BRs), glycinebetaine (GB) and nitrous oxide (NO) can induce abiotic stresses tolerance in many crops. In this time course study, we appraised the comparative role of all these substances to improve the drought tolerance in rice (Oryza sativa L.) cultivar Super-Basmati. Plants were subjected to drought stress at four leaf stage (4 weeks after emergence) by maintaining soil moisture at 50 % of field capacity. Pre-optimized concentrations of GB (150 mg l,1), SA (100 mg l,1), NO (100 ,mol l,1 sodium nitroprusside as NO donor), BR (0.01 ,m 24-epibrassinolide) and spermine (Spm; 10 ,m) were foliar sprayed at five-leaf stage (5 weeks after emergence). There were two controls both receiving no foliar spray, viz. well watered (CK1) and drought stressed (CK2). There was substantial reduction in allometric response of rice, gas exchange and water relation attributes by drought stress. While drought stress enhanced the H2O2, malondialdehyde (MDA) and relative membrane permeability, foliar spray of all the chemicals improved growth possibly because of the improved carbon assimilation, enhanced synthesis of metabolites and maintenance of tissue water status. Simultaneous reduction in H2O2 and MDA production was also noted in the plants treated with these substances. Drought tolerance was sturdily associated with the greater tissue water potential, increased synthesis of metabolites and enhanced capacity of antioxidant system. Of all the chemicals, foliar spray with Spm was the most effective followed by BR. [source]


    Exogenously Applied Nitric Oxide Enhances the Drought Tolerance in Fine Grain Aromatic Rice (Oryza sativa L.)

    JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 4 2009
    M. Farooq
    Abstract Drought stress is a severe threat to the sustainable rice production, which causes oxidative damage and disturbs plant water relations, while exogenously applied nitric oxide (NO) may have the potential to alleviate these effects in rice plants. In this study, the role of NO to improve drought tolerance in fine grain aromatic rice (Oryza sativa L. cv. Basmati 2000) was evaluated. Sodium nitroprusside, a NO donor, was used at 50, 100 and 150 ,mol l,1 both as seed priming and foliar spray. To prime, the seeds were soaked in aerated NO solution of respective solution for 48 h and dried back to original weight. Primed and non-primed seeds were sown in plastic pots with normal irrigation in a greenhouse. At four leaf stage, plants were subjected to drought stress except the controls, which were kept at full field capacity. Drought was maintained at 50 % of field capacity by watering when needed. Two controls were maintained; both receiving no NO treatments as foliar application or seed treatment, one under drought conditions and the other under well-watered conditions. Drought stress seriously reduced the rice growth, but both methods of NO application alleviated the stress effects. Drought tolerance in rice was strongly related to the maintenance of tissue water potential and enhanced capacity of antioxidants, improved stability of cellular membranes and enhanced photosynthetic capacity, plausibly by signalling action of NO. Foliar treatments proved more effective than the seed treatments. Among NO treatment, 100 ,mol l,1 foliar spray was more effective. [source]


    Insulin restores glucose inhibition of adenosine transport by increasing the expression and activity of the equilibrative nucleoside transporter 2 in human umbilical vein endothelium

    JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006
    Gonzalo Muoz
    L -Arginine transport and nitric oxide (NO) synthesis (L -arginine/NO pathway) are stimulated by insulin, adenosine or elevated extracellular D -glucose in human umbilical vein endothelial cells (HUVEC). Adenosine uptake via the human equilibrative nucleoside transporters 1 (hENT1) and 2 (hENT2) has been proposed as a mechanism regulating adenosine plasma concentration, and therefore its vascular effects in human umbilical veins. Thus, altered expression and/or activity of hENT1 or hENT2 could lead to abnormal physiological plasma adenosine level. We have characterized insulin effect on adenosine transport in HUVEC cultured in normal (5 mM) or high (25 mM) D -glucose. Insulin (1 nM) increased overall adenosine transport associated with higher hENT2-, but lower hENT1-mediated transport in normal D -glucose. Insulin increased hENT2 protein abundance in normal or high D -glucose, but reduced hENT1 protein abundance in normal D -glucose. Insulin did not alter the reduced hENT1 protein abundance, but blocked the reduced hENT1 and hENT2 mRNA expression induced by high D -glucose. Insulin effect on hENT1 mRNA expression in normal D -glucose was blocked by NG -nitro- L -arginine methyl ester (L-NAME, NO synthase inhibitor) and mimicked by S -nitroso- N -acetyl- L,D -penicillamine (SNAP, NO donor). L-NAME did not block insulin effect on hENT2 expression. In conclusion, insulin stimulation of overall adenosine transport results from increased hENT2 expression and activity via a NO-independent mechanism. These findings could be important in hyperglycemia-associated pathological pregnancies, such as gestational diabetes, where plasma adenosine removal by the endothelium is reduced, a condition that could alter the blood flow from the placenta to the fetus affecting fetus growth and development. J. Cell. Physiol. 209: 826,835, 2006. 2006 Wiley-Liss, Inc. [source]


    Non-specific immune response of turbot, Scophthalmus maximus (L.), experimentally infected with a pathogenic Vibrio pelagius

    JOURNAL OF FISH DISEASES, Issue 6 2003
    L Villamil
    Abstract The effect of a pathogenic Vibrio pelagius, isolated during a mass mortality of turbot larvae, on the non-specific immune response of turbot, Scophthalmus maximus (L.), macrophages was studied both in vitro and in vivo. The in vitro treatment of head kidney (HK) macrophages with viable V. pelagius caused a significant inhibition of the chemiluminescence (CL) response in comparison with untreated macrophages, while incubation with heat-killed bacteria did not affect this response. In vivo, the intraperitoneal injection of V. pelagius resulted in a significant inhibition of the CL response in infected fish at days 1 and 4 post-infection compared with the control fish response. The HK macrophage nitric oxide (NO) production was enhanced by in vitro incubation with intermediate doses of viable V. pelagius (5 103 and 5 104 bacteria mL,1) and higher doses of the heat-killed bacteria (5 104,5 106 bacteria mL,1). In both cases, the NO inhibitorN- , -nitro-L-arginine was capable of down-regulating the specific NO induction caused by incubation with the bacterial treatments. In contrast, incubation with ECPs at higher doses caused a reduction in NO production. In vivo, a significant enhancement in NO production was also observed in macrophage supernatants at day 10 post-infection. Lysozyme concentration in the serum was also significantly increased in the experimentally infected fish at days 4 and 10 post-injection. In addition, viable V. pelagius and its ECPs significantly reduced HK macrophage viability in vitro, whereas no significant differences in viability were observed during the incubation with heat-killed bacteria. As NO production was enhanced in the experimentally infected fish, the inhibitory effect of the NO donor, S-nitroso-acetyl-penicillamine (SNAP), was tested in vitro in a cell-free assay. The results showed that growth of V. pelagius was significantly inhibited using SNAP at a high concentration (1 mm). [source]


    NMDA-induced acetylcholine release in mouse striatum: role of NO synthase isoforms

    JOURNAL OF NEUROCHEMISTRY, Issue 6 2002
    Marie-Luise Buchholzer
    Abstract Striatal cholinergic interneurons are stimulated by glutamatergic inputs from thalamus and cortex via NMDA receptors. The present microdialysis study was designed to characterize the role of nitric oxide (NO) in this process and to identify the NO synthase (NOS) isoform responsible for this effect. For this purpose, we studied the effects of NMDA and 3-morpholino sydnonimine (SIN-1) perfusions on the release of acetylcholine (ACh) in mouse striatum. In wild-type C57/Bl6 mice, perfusion of NMDA (100 m) induced a two-fold stimulation of ACh release. This effect was attenuated in mice lacking endothelial NOS but was completely absent in mice lacking neuronal NOS. Local perfusion of SIN-1 (300 m), an NO donor, increased ACh release by more than two-fold in all three mouse lines. We conclude that NO synthesized by neuronal NOS provides a nitrergic link in the glutamatergic stimulation of striatal cholinergic interneurons. [source]


    Influence of progesterone on myometrial contractility in pregnant mice treated with lipopolysaccharide

    JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2007
    Hiroshi Anbe
    Abstract Aim:, To evaluate the effect of progesterone on interleukin (IL)-6, prostaglandin (PG) E2 and nitric oxide (NO) metabolite (NOx) production and contractile activity by NO in pregnant mice treated with lipopolysaccharide (LPS). Methods:, Pregnant C57BL mice on day 14 of gestation were killed 6 h after i.p. injection of LPS (400 ,g/kg) or vehicle. Progesterone (2 mg) was subcutaneously injected 2 h before LPS treatment. Uterine rings were equilibrated in Krebs-Henseleit solution (37C) bubbled with 20% O2 and 5% CO2 (pH 7.4) for sampling and isometric tension recording. IL-6, PGE2 and NOx productions were measured from the bathing solution. Changes in spontaneous contractile activity in response to cumulative concentrations of l -arginine, diethylamine/nitric oxide (DEA/NO, the NO donor), and 8-bromo-cGMP (8-br-cGMP) were compared. Integral contractile activity over 10 min after each concentration was calculated and expressed as percentage change from basal activity. Statistical analyses were performed using one-way anova followed by Dunnett's test (significance was defined as P < 0.05). Results:, Interleukin-6 (34.7 6.0 pg/g tissue), PGE2 (66.8 6.7 pg/g tissue) and NOx (51.0 5.4 pmol/2 mL/g wet tissue) production were significantly stimulated by LPS treatment (138.2 23.2, 147.0 29.0, 98.6 16.2, respectively; P < 0.05). l -arginine, DEA/NO and 8-br-cGMP concentration-dependently inhibited spontaneous contractions in uterine rings both in LPS-treated and -untreated animals. Treatment with LPS significantly attenuated the maximal inhibition induced by l -arginine, DEA/NO and 8-br-cGMP in uterine rings from pregnant mice. Progesterone significantly decreased the levels of IL-6 production (74.9 12.1, P < 0.05), but not PGE2 and NOx production, and contractile responses by l -arginine, DEA/NO and 8-br-cGMP. Conclusions:, The administration of LPS is associated with increases in IL-6, PGE2 and NO, and these increases may or may not have a role to play in LPS-induced preterm labor. Progesterone reduced the LPS-induced increase in IL-6 production and this may be one of the ways that progesterone reduces the risk of preterm labor. [source]


    In-vitro anti-inflammatory effect of Eucalyptus globulus and Thymus vulgaris: nitric oxide inhibition in J774A.1 murine macrophages

    JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2004
    E. Vigo
    ABSTRACT It is well known that nitric oxide (NO) plays an important role in the pathogenesis of inflammatory diseases. Eucalyptus globulus Labill. and Thymus vulgaris L. have been used in traditional medicine in the treatment of bronchitis, asthma and other respiratory diseases. The present study focuses on the effects of these two extracts on NO production induced by lipopolysaccharide (LPS) and interferon-, (IFN-,) in the murine macrophage cell line J774A.1. In addition, cell viability, scavenging activity and inducible nitric oxide synthase (iNOS) mRNA expression were evaluated. E. globulus and T. vulgaris extracts significantly inhibited the enhanced production of NO induced by LPS and IFN-, in a dose-dependent manner. Treatment with these two extracts did not reduce cell viability at any dose used. Both plant extracts showed significant scavenging of NO radicals released by an NO donor, PAPANONOate. Results also show that pre-treatment with E. globulus and T. vulgaris extracts significantly inhibits iNOS mRNA expression. This study thus suggests that the inhibition of net NO production by these two extracts may be due to their NO scavenging activity and/or their inhibitory effects on iNOS gene expression. [source]


    Alcohol Up-Regulates TLR2 Through a NO/cGMP Dependent Pathway

    ALCOHOLISM, Issue 1 2010
    Kristina L Bailey
    Background:, Heavy alcohol consumption is associated with severe bronchitis. This is likely related to increased inflammation in the airways of alcohol abusers. Toll-like receptor 2 (TLR2) is an important mediator of inflammation in the airway epithelium. TLR2 initiates an inflammatory cascade in response to gram-positive bacteria. We have previously shown that alcohol up-regulates TLR2 in the airway epithelium. However, the mechanism of alcohol-mediated up-regulation of TLR2 has not been identified. Methods:, A human airway epithelial cell line, 16HBE14o,, was exposed to biologically relevant concentrations of alcohol (100 mM) in the presence and absence of N, -Nitro- l -arginine methyl ester hydrochloride, a nitric oxide (NO) synthase inhibitor; and Rp-8-Br-cGMP-S, an antagonist analogue of cGMP. TLR2 was measured using real-time PCR and Western blots. In addition, 16HBE14o, cells were incubated with sodium nitroprusside (SNP), an NO donor, and 8-Br-cGMP, a cGMP analogue. TLR2 was measured using real-time PCR. Results:,N, -Nitro- l -arginine methyl ester hydrochloride blocked the alcohol-mediated up-regulation of TLR2. This indicates that NO plays a key role in alcohol's up-regulation of TLR2. SNP, a NO donor, up-regulated TLR2. Rp-8-Br-CGMP-S attenuated alcohol's up-regulation of TLR2, suggesting that NO was working through cGMP/PKG. 8-Br-cGMP up-regulated TLR2, also demonstrating the importance of cGMP/PKG. Conclusions:, Alcohol up-regulates TLR2 through a NO/cGMP/PKG dependent pathway in the airway epithelium. This is an important observation in the understanding how alcohol modulates airway inflammation. In addition, this is the first time that cyclic nucleotides have been shown to play a role in the regulation of TLR2. [source]


    Role of inducible nitric oxide synthase in dextran sulphate sodium-induced colitis

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2000
    Y. Yoshida
    Summary Background: Different authors have postulated both toxic and protective effects for nitric oxide (NO) in the pathophysiology of active inflammation. Aim: To examine the role of NO, especially that produced by the inducible form of nitric oxide synthase (iNOS), by investigating the effects of NOS inhibitors and NO donors on inflammation in experimental acute colitis. Methods: Acute colitis was induced in rats by dextran sulphate sodium (DSS). White blood cell counts and levels of thiobarbituric acid reactants in the portal blood were determined, as were histological changes in the colonic mucosa. We then evaluated the effects of NG -nitro- l -arginine methyl ester ( l -NAME), aminoguanidine (AG) and an NO donor on DSS-induced changes in these inflammatory parameters. Results and Conclusions: Inhibition of NO production by either l -NAME or AG worsened DSS-induced inflammation, suggesting a protective role for NO in acute colitis. On the other hand, a NO donor also exaggerated DSS-induced inflammatory parameters, suggesting that acute colitis may be aggravated by either too much or too little NO. These results suggest that medical treatment of ulcerative colitis must aim for maintenance of appropriate NO levels in the intestinal mucosa. [source]


    Nitric oxide modulation of low-density mononuclear cell transendothelial migration

    MICROSURGERY, Issue 5 2005
    J.S. Isenberg M.D., M.P.H.
    The blood-endothelial cell interface is a region of significant importance in many physiologic and pathologic processes. Blood-borne macromolecules and cells gain access to the subendothelial space and extravascular tissues by traversing the endothelium. Yet the various factors responsible for modulation of this process remain only partially elucidated. Several agents were found to be involved in this process, including nitric oxide (NO) and vascular endothelial growth factor (VEGF). It is known that under stress conditions (e.g., inflammation), NO can modulate the permeability of endothelial-cell monolayers to low-density mononuclear cells (LDMNCs). However, it is not known if NO can modulate such effects in the absence of inflammatory stimulation. In the present study, we utilized a Transwell chamber model to examine endothelial-cell monolayer permeability to LDMNCs in the absence of inflammatory stimuli. We noted that NO donor and L-arginine increased transendothelial-cell migration, whereas nitric oxide synthase (NOS) inhibition decreased migration. These effects were not significantly abrogated by VEGF antibody, suggesting that they were not VEGF-dependent. 2005 Wiley-Liss, Inc. Microsurgery 25:452,456, 2005. [source]


    Microinjection of glutamate into dorsal motor nucleus of the vagus excites gallbladder motility through NMDA receptor , nitric oxide , cGMP pathway

    NEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2004
    C. Y. Liu
    Abstract, We have reported that both glutamate and nitric oxide (NO) participated in the regulation of gallbladder motility in dorsal motor nucleus of the vagus (DMV). The aim of this study is to investigate the type of receptor in DMV that mediates the excitatory effect of glutamate on gallbladder motility and the correlation between the glutamate and NO. A frog bladder connected with a force transducer was inserted into the gallbladder to record the change of gallbladder pressure. Glutamate (65 mmol L,1, 100 nL) microinjected into DMV significantly increased the strength of gallbladder phasic contraction. This effect was abolished by ketamine (180 mmol L,1, 100 nL), the specific N -methyl- d -aspartic acid (NMDA) receptor antagonist, but was not influenced by 6-cyaon-7-nitroquinoxaline-2,3-(1H,4H)-dione (CNQX) (180 mmol L,1, 100 nL), the non-NMDA ionotropic receptor antagonist. NG -nitro- l -arginine-emthyl (l -NAME) (1 mol L,1, 100 nL), the nitric oxide synthase (NOS) inhibitor, reversed the excitatory effect of glutamate on gallbladder motility. Microinjection of sodium nitroprusside (SNP), the NO donor, into DMV enhanced the gallbladder motility, and this effect was not modulated by ketamine. Microinjection of NMDA (5 mmol L,1, 100 nL) increased the strength of gallbladder phasic contraction, and this effect was attenuated by methylene blue (100 mmol L,1, 100 nL), the soluble guanylate cyclase inhibitor. These results suggest that glutamate regulate the gallbladder motility through the NMDA receptor , NO , cGMP pathway in DMV. [source]


    Prostaglandin F2, Stimulates Endothelial Nitric Oxide Synthase Depending on the Existence of Bovine Granulosa Cells: Analysis by Co-culture System of Endothelial Cells, Smooth Muscle Cells and Granulosa Cells

    REPRODUCTION IN DOMESTIC ANIMALS, Issue 5 2008
    K Shirasuna
    Contents Prostaglandin F2, (PGF2,) induces luteolysis in the mid but not in the early luteal phase; despite this, both the early and the mid corpus luteum (CL) have PGF2, receptor (FPr). We previously indicated that the luteal blood flow surrounding the CL drastically increases prior to a decrease of progesterone (P) in the cows, suggesting that an acute increase of luteal blood flow may be an early sign of luteolysis in response to PGF2, and that this may be induced by a vasorelaxant nitric oxide (NO). The aim of this study was to investigate the luteal stage-dependent and the site-restricted effect of PGF2, and NO on the mRNA expressions and P secretion. To mimic the local luteal region both of peripheral and central areas of the CL, we utilized co-cultures using bovine aorta endothelial cells (EC), smooth muscle cells (SMC) and luteinizing granulosa cells (GC) or fully-luteinized GC. PGF2, stimulated the expression of endothelial NO synthase (eNOS) mRNA at 0.5 h in mix-cultures of EC and SMC with fully-luteinized GC but not with luteinizing GC. The expression of eNOS mRNA in EC was increased by PGF2, at 1 h only when EC was cultured together with fully-luteinized GC but not with luteinizing GC. In all co-cultures, PGF2, did not affect the mRNA expression of FPr. Treatment of NO donor inhibited P secretion at 0.5 h. In conclusion, the present study suggests that the coexistence of the mature luteal cells (fully-luteinized GC) with EC/SMC may be crucial for acquiring functional NO synthesis induced by PGF2,. [source]


    Development of nitrergic neurons in the nervous system of the locust embryo

    THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 8 2010
    Michael Stern
    We followed the development of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) system during locust embryogenesis in whole mount nervous systems and brain sections by using various cytochemical techniques. We visualized NO-sensitive neurons by cGMP immunofluorescence after incubation with an NO donor in the presence of the soluble guanylyl cyclase (sGC) activator YC-1 and the phosphodiesterase-inhibitor isobutyl-methyl-xanthine (IBMX). Central nervous system (CNS) cells respond to NO as early as 38% embryogenesis. By using the NADPH-diaphorase technique, we identified somata and neurites of possible NO-synthesizing cells in the CNS. The first NADPH-diaphorase-positive cell bodies appear around 40% embryogenesis in the brain and at 47% in the ventral nerve cord. The number of positive cells reaches the full complement of adult cells at 80%. In the brain, some structures, e.g., the mushroom bodies acquire NADPH-diaphorase staining only postembryonically. Immunolocalization of L-citrulline confirmed the presence of NOS in NADPH-diaphorase-stained neurons and, in addition, indicated enzymatic activity in vivo. In whole mount ventral nerve cords, citrulline immunolabeling was present in varying subsets of NADPH-diaphorase-positive cells, but staining was very variable and often weak. However, in a regeneration paradigm in which one of the two connectives between ganglia had been crushed, strong, reliable staining was observed as early as 60% embryogenesis. Thus, citrulline immunolabeling appears to reflect specific activity of NOS. However, in younger embryos, NOS may not always be constitutively active or may be so at a very low level, below the citrulline antibody detection threshold. For the CNS, histochemical markers for NOS do not provide conclusive evidence for a developmental role of this enzyme. J. Comp. Neurol. 518:1157,1175, 2010. 2010 Wiley-Liss, Inc. [source]


    Development of nitrergic neurons in the nervous system of the locust embryo

    THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 8 2010
    Michael Stern
    Abstract We followed the development of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) system during locust embryogenesis in whole mount nervous systems and brain sections by using various cytochemical techniques. We visualized NO-sensitive neurons by cGMP immunofluorescence after incubation with an NO donor in the presence of the soluble guanylyl cyclase (sGC) activator YC-1 and the phosphodiesterase-inhibitor isobutyl-methyl-xanthine (IBMX). Central nervous system (CNS) cells respond to NO as early as 38% embryogenesis. By using the NADPH-diaphorase technique, we identified somata and neurites of possible NO-synthesizing cells in the CNS. The first NADPH-diaphorase-positive cell bodies appear around 40% embryogenesis in the brain and at 47% in the ventral nerve cord. The number of positive cells reaches the full complement of adult cells at 80%. In the brain, some structures, e.g., the mushroom bodies acquire NADPH-diaphorase staining only postembryonically. Immunolocalization of L-citrulline confirmed the presence of NOS in NADPH-diaphorase-stained neurons and, in addition, indicated enzymatic activity in vivo. In whole mount ventral nerve cords, citrulline immunolabeling was present in varying subsets of NADPH-diaphorase-positive cells, but staining was very variable and often weak. However, in a regeneration paradigm in which one of the two connectives between ganglia had been crushed, strong, reliable staining was observed as early as 60% embryogenesis. Thus, citrulline immunolabeling appears to reflect specific activity of NOS. However, in younger embryos, NOS may not always be constitutively active or may be so at a very low level, below the citrulline antibody detection threshold. For the CNS, histochemical markers for NOS do not provide conclusive evidence for a developmental role of this enzyme. J. Comp. Neurol. 518:1157,1175, 2010. 2009 Wiley-Liss, Inc. [source]


    Acute physical exercise reverses S -nitrosation of the insulin receptor, insulin receptor substrate 1 and protein kinase B/Akt in diet-induced obese Wistar rats

    THE JOURNAL OF PHYSIOLOGY, Issue 2 2008
    Jos R. Pauli
    Early evidence demonstrates that exogenous nitric oxide (NO) and the NO produced by inducible nitric oxide synthase (iNOS) can induce insulin resistance. Here, we investigated whether this insulin resistance, mediated by S -nitrosation of proteins involved in early steps of the insulin signal transduction pathway, could be reversed by acute physical exercise. Rats on a high-fat diet were subjected to swimming for two 3 h-long bouts, separated by a 45 min rest period. Two or 16 h after the exercise protocol the rats were killed and proteins from the insulin signalling pathway were analysed by immunoprecipitation and immunoblotting. We demonstrated that a high-fat diet led to an increase in the iNOS protein level and S -nitrosation of insulin receptor , (IR,), insulin receptor substrate 1 (IRS1) and Akt. Interestingly, an acute bout of exercise reduced iNOS expression and S -nitrosation of proteins involved in the early steps of insulin action, and improved insulin sensitivity in diet-induced obesity rats. Furthermore, administration of GSNO (NO donor) prevents this improvement in insulin action and the use of an inhibitor of iNOS (l- N6 -(1-iminoethyl)lysine; l -NIL) simulates the effects of exercise on insulin action, insulin signalling and S -nitrosation of IR,, IRS1 and Akt. In summary, a single bout of exercise reverses insulin sensitivity in diet-induced obese rats by improving the insulin signalling pathway, in parallel with a decrease in iNOS expression and in the S -nitrosation of IR/IRS1/Akt. The decrease in iNOS protein expression in the muscle of diet-induced obese rats after an acute bout of exercise was accompanied by an increase in AMP-activated protein kinase (AMPK) activity. These results provide new insights into the mechanism by which exercise restores insulin sensitivity. [source]


    Real-time measurement of nitric oxide in single mature mouse skeletal muscle fibres during contractions

    THE JOURNAL OF PHYSIOLOGY, Issue 1 2007
    Deborah Pye
    Nitric oxide (NO) is thought to play multiple roles in skeletal muscle including regulation of some adaptations to contractile activity, but appropriate methods for the analysis of intracellular NO activity are lacking. In this study we have examined the intracellular generation of NO in isolated single mature mouse skeletal muscle fibres at rest and following a period of contractile activity. Muscle fibres were isolated from the flexor digitorum brevis muscle of mice and intracellular NO production was visualized in real-time using the fluorescent NO probe 4-amino-5-methylamino-2,,7,-difluorofluorescein diacetate (DAF-FM DA). Some leakage of DAF-FM was apparent from fibres loaded with the probe, but they retained sufficient probe to respond to changes in intracellular NO following addition of the NO donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)- N -methyl-1-propanamine (NOC-7) up to 30 min after loading. Electrically stimulated contractions in isolated fibres increased the rate of change in DAF-FM fluorescence by ,48% compared to non-stimulated fibres (P < 0.05) and the rate of change in DAF-FM fluorescence in the stimulated fibres returned to control values by 5 min after contractions. Treatment of isolated fibres with the NO synthase inhibitors NG -nitro- l -arginine methyl ester hydrochloride (l -NAME) or NG -monomethyl- l -arginine (l -NMMA) reduced the increase in DAF-FM fluorescence observed in response to contractions of untreated fibres. Treatment of fibres with the cell-permeable superoxide scavenger 4,5-dihydroxy-1,3-benzenedisulphonic acid (Tiron) also reduced the increase in fluorescence observed during contractions suggesting that superoxide, or more probably peroxynitrite, contributes to the fluorescence observed. Thus this technique can be used to examine NO generation in quiescent and contracting skeletal muscle fibres in real time, although peroxynitrite and other reactive nitrogen species may potentially contribute to the fluorescence values observed. [source]


    Spontaneous Ca2+ Waves in Rabbit Corpus Cavernosum: Modulation by Nitric Oxide and cGMP

    THE JOURNAL OF SEXUAL MEDICINE, Issue 4 2009
    Gerard P. Sergeant PhD
    ABSTRACT Introduction., Detumescent tone and subsequent relaxation by nitric oxide (NO) are essential processes that determine the erectile state of the penis. Despite this, the mechanisms involved are incompletely understood. It is often assumed that the tone is associated with a sustained high cytosolic Ca2+ level in the corpus cavernosum smooth muscle cells, however, an alternative possibility is that oscillatory Ca2+ signals regulate tone, and erection occurs as a result of inhibition of Ca2+ oscillations by NO. Aims., The aim of this study is to determine if smooth muscle cells displayed spontaneous Ca2+ oscillations and, if so, whether these were regulated by NO. Methods., Male New Zealand white rabbits were euthanized and smooth muscle cells were isolated by enzymatic dispersal for confocal imaging of intracellular Ca2+ (using fluo-4AM) and patch clamp recording of spontaneous membrane currents. Thin tissue slices were also loaded with fluo-4AM for live imaging of Ca2+. Main Outcome Measure., Cytosolic Ca2+ was measured in isolated smooth muscle cells and tissue slices. Results., Isolated rabbit corpus cavernosum smooth muscle cells developed spontaneous Ca2+ waves that spread at a mean velocity of 65 m/s. Dual voltage clamp/confocal recordings revealed that each of the Ca2+ waves was associated with an inward current typical of the Ca2+ -activated Cl - currents developed by these cells. The waves depended on an intact sarcoplasmic reticulum Ca2+ store, as they were blocked by cyclopiazonic acid (Calbiochem, San Diego, CA, USA) and agents that interfere with ryanodine receptors and IP3 -mediated Ca2+ release. The waves were also inhibited by an NO donor (diethylamine NO; Tocris Bioscience, Bristol, Avon, UK), 3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole (YC-1) (Alexis Biochemicals, Bingham, Notts, UK), 8-bromo-cyclic guanosine mono-phosphate (Tocris), and sildenafil (Viagra, Pfizer, Sandwich, Kent, UK). Regular Ca2+ oscillations were also observed in whole tissue slices where they were clearly seen to precede contraction. This activity was also markedly inhibited by sildenafil, suggesting that it was under NO regulation. Conclusions., These results provide a new basis for understanding detumescent tone in the corpus cavernosum and its inhibition by NO. Sergeant GP, Craven M, Hollywood MA, McHale NG, and Thornbury KD. Spontaneous Ca2+ waves in rabbit corpus cavernosum: Modulation by nitric oxide and cGMP. J Sex Med **;**:**,**. [source]


    Opposite effects of endogenous nitric oxide and prostaglandin F2, in the rat mesenteric bed

    AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2003
    H. A. Peredo
    Summary 1 The relationship between the effects of endogenous nitric oxide (NO) and prostanoids on the noradrenaline (NA)-induced contractions and the mechanisms involved were investigated in the rat perfused mesenteric bed, using NG -nitro- l -arginine methyl ester (l -NAME), a NO synthase inhibitor and sodium nitroprusside (SNP), a NO donor. 2 The constrictor responses to NA were reduced to 50% by the cyclooxygenase inhibitor 10 ,m indomethacin as well as by 1 ,m SNP. When indomethacin and SNP were perfused simultaneously the contractions were further reduced. 3 The NA-induced contractions were increased by the addition of 400 ,ml -NAME and the addition of either indomethacin or SNP abolished such increases. The simultaneous perfusion of both agents further reduced the contractions. 4 Removal of the endothelium increased NA-induced contractions to a similar extent as l -NAME and this increase was abolished by indomethacin as well as by SNP. 5 The perfusion of 10 ,m NA augmented the release of prostaglandin (PG) F2, by the mesenteric bed without modifications in any other prostanoid. In the presence of l -NAME, this effect was further increased. However, SNP abolished the NA-induced stimulation of PGF2, release. 6 In de-endothelialized preparations NA also stimulated PGF2, production as observed in intact preparations. This effect was more marked in the presence of l -NAME; in contrast, SNP abolished the stimulation. 7 In conclusion, the present results suggest an opposite action between NO and PGF2, on the NA-induced contractions in the rat mesenteric bed. [source]


    Effect of intermittent and continuous exposure to electromagnetic fields on cultured hippocampal cells

    BIOELECTROMAGNETICS, Issue 2 2002
    A. Boland
    Abstract This study was designed to assess the effect of 50 Hz electromagnetic fields (EMFs) on hippocampal cell cultures in the presence or absence of either sodium nitroprusside (SNP, a NO donor) or Fe2+ induced oxidative stress. One week old cultured rat hippocampal cells were exposed to either intermittent EMFs (IEMFs, 50 Hz, 0,5 mT, 1 min ON/OFF cycles, repeated 10 times every 2 h, 6 times/day during 48 h) or continuous EMFs (CEMFs, 50 Hz, 0,5 mT for 48 h). In a second set of experiments, the effect on such EMFs applied in combination with oxidative stress induced by 0.5 ,M Fe2+ or SNP was estimated. At the end of both sets of experiments, cell mortality was assessed by lactate dehydrogenase measurements (LDH). Neither type of exposure to EMFs was observed to modify the basal rate of cell mortality. The exposure to CEMFs in presence of either NO or Fe2+ did not induce any significant increase in cell death. However, when cells were exposed to EMFs in the presence of NO, we observed a significant increase in cell death of 11 and 23% (P<0.001) at 2.5 and 5 mT, respectively. This effect had some specificity because IEMFs did not modify the effect of Fe2+ on cell mortality. Although the effects of IEMFs reported in this study were only observed at very high intensities, our model may prove valuable in trying to identify one cellular target of EMFs. Bioelectromagnetics 23:97,105, 2002. 2002 Wiley-Liss, Inc. [source]