Endogenous NO (endogenous + no)

Distribution by Scientific Domains

Terms modified by Endogenous NO

  • endogenous no production

  • Selected Abstracts

    The in vitro effects of melatonin on human sperm function and its scavenging activities on NO and ROS

    ANDROLOGIA, Issue 2 2010
    S. S. Du Plessis
    Summary Various systems of antioxidants exist endogenously in the body to help protect it against free radical damage by scavenging excessive ROS and RNS. Melatonin, a hormone secreted by the pineal gland, and responsible for controlling the circadian rhythm, is one such endogenous antioxidant. Melatonin has been reported to be present in human seminal fluid, but its antioxidant activities in semen are rather contradictory. This study aimed at establishing the effects of melatonin treatment on human spermatozoa. Spermatozoa were incubated with 2 mm melatonin (120 min, 37 C, 5% CO2) after which motility parameters were measured by computer aided motility analysis, while cell viability (PI), intracellular NO (DAF-2/DA) and ROS (DCFH-DA) were assessed using flow cytometry. In vitro melatonin treated samples (n = 12) showed a significantly higher percentage of motile, progressive motile and rapid cells, while simultaneously reducing the number of nonviable spermatozoa when compared with the control. Endogenous NO was significantly decreased, but no effect was observed on ROS levels. From these results, it can be concluded that melatonin was able to directly or indirectly scavenge NO, as indicated by the reduction in 4,5-diaminofluorescein-2/diacetate fluorescence. Future studies will indicate whether melatonin treatment during sperm preparation techniques could protect spermatozoa from excessive NO production. [source]

    Electrochemical Nitric Oxide Sensors for Biological Samples , Principle, Selected Examples and Applications

    ELECTROANALYSIS, Issue 1 2003
    Fethi Bedioui
    Abstract The discoveries made in the 1980s that NO could be synthesized by mammalian cells and could act as physiological messenger and cytotoxic agent had elevated the importance of its detection. The numerous properties of NO, that enable it to carry out its diverse functions, also present considerable problems when attempting its detection and quantification in biological systems. Indeed, its total free concentration in physiological conditions has been established to be in nanomolar range. Thus, detection of nitric oxide remains a challenge, pointing out the difficult dual requirements for specificity and sensitivity. Exception made for the electrochemical techniques, most of the approaches (namely UV-visible spectroscopy, fluorescence, electron paramagnetic resonance spectroscopy) use indirect methods for estimating endogenous NO, relying on measurements of secondary species such as nitrite and nitrate or NO-adducts. They also suffer from allowing only ex situ measurements. So, the only strategies that allow a direct and in vivo detection of NO are those based on the use of ultramicroelectrodes. The reality is that surface electrode modification is needed to make the ultramicroelectrode material selective for NO. Therefore, the design of modified electrode surfaces using organized layers is very attractive and provides the ideal strategy. This review addresses a global description of the various approaches that have involved chemically modified microelectrodes specially designed for the electrochemical detection of NO in biological media. Selected significant examples of applications in biological tissues are also reported in order to highlight the importance of this approach in having new insights into the modulatory role of NO in physiology and pathophysiology. [source]

    A 4-trifluoromethyl derivative of salicylate, triflusal, stimulates nitric oxide production by human neutrophils: role in platelet function

    De Miguel
    Background The thrombotic process is a multicellular phenomenon in which not only platelets but also neutrophils are involved. Recent in vitro studies performed in our laboratory have demonstrated that triflusal, a 4-trifluoromethyl derivative of salicylate, reduced platelet aggregation not only by inhibiting thromboxane A2 production but also by stimulating nitric oxide (NO) generation by neutrophils. The aim of the present study was to evaluate whether oral treatment of healthy volunteers with triflusal could modify the ability of their neutrophils to produce NO and to test the role of the NO released by neutrophils in the modulation of ADP-induced platelet aggregation and ,-granule secretion. Methods The study was performed in 12 healthy volunteers who were orally treated with triflusal (600 mg day,1) for 5 days. Flow cytometric detection of platelet surface expression of P-selectin was used as a measure of the ability of platelets to release the contents of their ,-granules. Results After treatment with triflusal, there was an increase in NO production by neutrophils and an increase in endothelial nitric oxide synthase (eNOS) protein expression in neutrophils. A potentiation of the inhibition of platelet aggregation by neutrophils was reversed by incubating neutrophils with both an l -arginine antagonist, NG -nitro- l -arginine methyl ester ( l -NAME) and an NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline 1-oxyl 3-oxide (C-PTIO). A slight decrease in P-selectin surface expression on platelets was found which was not modified by the presence of neutrophils and therefore by the neutrophil-derived NO. Exogenous NO released by sodium nitroprusside dose-dependently inhibited both ADP-stimulated ,-granule secretion and platelet aggregation. Therefore, platelet aggregation showed a greater sensitivity to be inhibited by exogenous NO than P-selectin expression. Conclusion Oral treatment of healthy volunteers with triflusal stimulated NO production and eNOS protein expression in their neutrophils. After triflusal treatment, the neutrophils demonstrated a higher ability to prevent ADP-induced platelet aggregation. However, the neutrophils and the endogenous NO generated by them failed to modify P-selectin expression in ADP-activated platelets. [source]

    Exogenous nitric oxide causes potentiation of hippocampal synaptic transmission during low-frequency stimulation via the endogenous nitric oxide,cGMP pathway

    Christelle L. M. Bon
    Abstract Nitric oxide (NO) is a putative participant in synaptic plasticity and demonstrations that exogenous NO can elicit the same plastic changes have been taken to support such a role. The experiments, carried out on the CA1 region of rat hippocampal slices, were aimed at testing this interpretation. A major component of tetanus-induced long-term potentiation (LTP) was lost in response to l -nitroarginine, which inhibits NO synthase, and 1H -[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ), which inhibits NO-sensitive soluble guanylyl cyclase (sGC). At 0.2 Hz afferent fibre stimulation, exogenous NO produced, concentration-dependently, a synaptic depression that reverted on washout to a persistent potentiation that occluded tetanus-induced LTP. The NO concentrations necessary (estimated in the 100-nm range), however, were mostly supramaximal for stimulating hippocampal slice sGC activity. Nevertheless the potentiation, but not the preceding depression, was blocked by ODQ. l -nitroarginine and an NMDA antagonist were similarly effective, indicating mediation by the endogenous NMDA receptor,NO synthase,sGC pathway. At a concentration normally too low to affect synaptic transmission but sufficient to stimulate sGC (estimated to be 50 nm), exogenous NO reversed the effect of l -nitroarginine and caused a potentiation which was blocked by ODQ. At a concentration inducing the depression/potentiation sequence, NO partially inhibited hippocampal slice oxygen consumption. It is concluded that, at physiological levels, exogenous NO can directly elicit a potentiation of synaptic transmission through sGC, provided that the synapses are suitably primed. At higher concentrations, NO inhibits mitochondrial respiration, which can result in an enduring synaptic potentiation due to secondary activation of the endogenous NO,cGMP pathway. [source]

    Detrimental role of endogenous nitric oxide in host defence against Sporothrix schenckii

    IMMUNOLOGY, Issue 4 2008
    Karla Simone S. Fernandes
    Summary We earlier demonstrated that nitric oxide (NO) is a fungicidal molecule against Sporothrix schenckii in vitro. In the present study we used mice deficient in inducible nitric oxide synthase (iNOS,/,) and C57BL/6 wild-type (WT) mice treated with N,-nitro-arginine (Nitro-Arg-treated mice), an NOS inhibitor, both defective in the production of reactive nitrogen intermediates, to investigate the role of endogenous NO during systemic sporotrichosis. When inoculated with yeast cells of S. schenckii, WT mice presented T-cell suppression and high tissue fungal dissemination, succumbing to infection. Furthermore, susceptibility of mice seems to be related to apoptosis and high interleukin-10 and tumour necrosis factor-, production by spleen cells. In addition, fungicidal activity and NO production by interferon-, (IFN-,) and lipopolysaccharide-activated macrophages from WT mice were abolished after fungal infection. Strikingly, iNOS,/, and Nitro-Arg-treated mice presented fungal resistance, controlling fungal load in tissues and restoring T-cell activity, as well as producing high amounts of IFN-, Interestingly, macrophages from these groups of mice presented fungicidal activity after in vitro stimulation with higher doses of IFN-,. Herein, these results suggest that although NO was an essential mediator to the in vitro killing of S. schenckii by macrophages, the activation of NO system in vivo contributes to the immunosuppression and cytokine balance during early phases of infection with S. schenckii. [source]

    Nitric oxide regulates BDNF release from nodose ganglion neurons in a pattern-dependent and cGMP-independent manner

    Hui-ya Hsieh
    Abstract Activity of arterial baroreceptors is modulated by neurohumoral factors, including nitric oxide (NO), released from endothelial cells. Baroreceptor reflex responses can also be modulated by NO signaling in the brainstem nucleus tractus solitarius (NTS), the primary central target of cardiovascular afferents. Our recent studies indicate that brain-derived neurotrophic factor (BDNF) is abundantly expressed by developing and adult baroreceptor afferents in vivo, and released from cultured nodose ganglion (NG) neurons by patterns of baroreceptor activity. Using electrical field stimulation and ELISA in situ, we show that exogenous NO nearly abolishes BDNF release from newborn rat NG neurons in vitro stimulated with single pulses delivered at 6 Hz, but not 2-pulse bursts delivered at the same 6-Hz frequency, that corresponds to a rat heart rate. Application of L-NAME, a specific inhibitor of endogenous NO synthases, does not have any significant effect on activity-dependent BDNF release, but leads to upregulation of BDNF expression in an activity-dependent manner. The latter effect suggests a novel mechanism of homeostatic regulation of activity-dependent BDNF expression with endogenous NO as a key player. The exogenous NO-mediated effect does not involve the cGMP-protein kinase G (PKG) pathway, but is largely inhibited by N-ethylmaleimide and TEMPOL that are known to prevent S-nitrosylation. Together, our current data identify previously unknown mechanisms regulating BDNF availability, and point to NO as a likely regulator of BDNF at baroafferent synapses in the NTS. 2009 Wiley-Liss, Inc. [source]

    Nitric oxide signalling in salivary glands

    Dagnia Looms
    Abstract Nitric oxide (NO) plays multiple roles in both intracellular and extracellular signalling mechanisms with implications for health and disease. This review focuses on the role of NO signalling in salivary secretion. Attention will be paid primarily to endogenous NO production in acinar cells resulting from specific receptor stimulation and to NO-regulated Ca2+ homeostasis. Due to the fact that NO readily crosses membranes by simple diffusion, endogenous NO may play a physiological role in processes as diverse as modifying the secretory output, controlling blood supply to the gland, modulating transmitter output from nerve endings, participating in the host defence barrier, and affecting growth and differentiation of surrounding tissue. Furthermore, the role of NO in the pathogenesis of human oral diseases will be considered. [source]

    ORIGINAL RESEARCH,BASIC SCIENCE: A Nitric Oxide-Releasing PDE5 Inhibitor Relaxes Human Corpus Cavernosum in the Absence of Endogenous Nitric Oxide

    Jasjit S. Kalsi BSc, MRCS
    ABSTRACT Introduction., In conditions with severe deficiency of endogenous nitric oxide (NO), such as long-term diabetes and cavernosal nerve injury, phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in the treatment of erectile dysfunction. NO-releasing PDE5 inhibitors could be an alternative therapeutic approach in such cases. Aim., We therefore aimed to compare sildenafil and NO-releasing sildenafil (NCX-911) in relaxing human corpus cavernosum in the absence or presence of endogenous NO. Methods., The two compounds were compared in reducing the phenylephrine-induced tone of human corpus cavernosum in the presence or absence of an inhibitor of NO synthase (L-NAME; 500 M) or an inhibitor of soluble guanylate cyclase (ODQ, 10 M). Results., NCX-911 was as potent as sildenafil in control conditions (EC50 = 733.1 94.4 nM and 800.7 155.8 nM, respectively). The potency of NCX-911 was not altered but that of sildenafil decreased significantly in the presence of L-NAME (EC50 = 980.4 106.7 nM and 2446.7 256.8 nM, respectively; P < 0.001 for sildenafil vs. control). Both compounds below 1 M failed to induce relaxation in the presence of ODQ (EC50 = 6578 1150 nM and 6488 938 nM for NCX-911 and sildenafil, respectively). Conclusion., These results show that the potency of NCX-911 was maintained unlike sildenafil in the absence of endogenous NO confirming the potential use of NO-releasing PDE5 inhibitors in NO-deficient conditions. [source]

    Platelet aggregation responses are critically regulated in vivo by endogenous nitric oxide but not by endothelial nitric oxide synthase

    C Tymvios
    Background and purpose:, Although exogenous nitric oxide (NO) clearly modifies platelet function, the role and the source of endogenous NO in vivo remain undefined. In addition, endothelial NO synthase (NOS-3) critically regulates vessel tone but its role in modulating platelet function is unclear. In this paper we have investigated the roles of endogenous NO and NOS-3 in regulating platelet function in vivo and determined the functional contribution made by platelet-derived NO. Experimental approach:, We used a mouse model for directly assessing platelet functional responses in situ in the presence of an intact vascular endothelium with supporting in vitro and molecular studies. Key results:, Acute NOS inhibition by N, -nitro-L-arginine methyl ester hydrochloride (L-NAME) enhanced platelet aggregatory responses to thrombin and platelets were shown to be regulated primarily by NO sources external to the platelet. Elevation of endogenous NOS inhibitors to mimic effects reported in patients with cardiovascular diseases did not enhance platelet responses. Platelet responsiveness following agonist stimulation was not modified in male or female NOS-3,/, mice but responses in NOS-3,/, mice were enhanced by L-NAME. Conclusions and implications:, Platelets are regulated by endogenous NO in vivo, primarily by NO originating from the environment external to the platelet with a negligible or undetectable role of platelet-derived NO. Raised levels of endogenous NOS inhibitors, as reported in a range of diseases were not, in isolation, sufficient to enhance platelet activity and NOS-3 is not essential for normal platelet function in vivo due to the presence of bioactive NO following deletion of NOS-3. [source]

    Nitric oxide (NO) modulation of PAF-induced cardiopulmonary action: interaction between NO synthase and cyclo-oxygenase-2 pathways

    Fulvia Fabi
    To further investigate into the mechanisms of PAF-induced cardiopulmonary actions, we examined the effects of the nitric oxide synthase (NOS) inhibitor L -N, -nitro- L -arginine (L -NNA), of the specific cyclooxygenase-2 (COX-2) inhibitor NS 398, and of the combined presence of both COX and NOS inhibitors on the PAF responses in the heart lung preparation of guinea-pig (HLP). In HLPs perfused with homologous blood, dose-response curves for the haemodynamic and bronchial effects of PAF (1 , 32 ng) were carried out in the absence or presence of L -NNA (200 ,M). L -NNA caused an increase in the resting pulmonary arterial pressure (PAP) without affecting the other basal values, and strongly potentiated the bronchoconstriction and pulmonary hypertension elicited by PAF. An enhancement of the PAF-induced actions on right atrial pressure (RAP) and cardiac output (CO) was also observed. All the effects of L -NNA were antagonized by L -arginine (2 mM). The presence of L -NNA in the perfusing blood of HLPs failed to affect the pulmonary hypertensive and bronchoconstrictor responses induced by the thromboxane A2 mimetic U46619 (0.05 , 1.6 ,g), 5-hydroxytryptamine (0.1 , 1.6 ,g), and histamine (0.1 , 1.6 ,g), thus suggesting that these PAF secondary mediators are not responsible for the hyper-responsiveness to PAF induced by L -NNA. Blocking COX-2 pathway with NS 398 (15 , 30 ,M) did not alter the cardiopulmonary resting variables. However, a reduction of the PAF-mediated pulmonary hypertension, but not of bronchoconstriction, was observed. When L -NNA was added to the perfusing medium of HLPs pre-treated with NS 398 or with indomethacin (15 ,M), the basal PAP values were enhanced. However, in the combined presence of COX and NOS inhibitors, only a slight increase in the hypertensive responses to the highest doses of PAF was observed, whereas the PAF mediated actions at bronchial and cardiac level were unaffected. This study indicates that (i) the cardiopulmonary actions induced by PAF are specifically modulated by endogenous NO through the NOS pathway, and (ii) COX-2 isoform is involved in the pulmonary hypertensive, but not bronchoconstrictor, effects of PAF. Furthermore, an interaction between PAF stimulated COX, particularly COX-2, and NOS pathways appears to take a functional role at both bronchial and cardiovascular level. British Journal of Pharmacology (2001) 134, 777,788; doi:10.1038/sj.bjp.0704311 [source]

    Introduction on the multifaceted roles of nitric oxide in the retina

    Multifaceted roles of nitric oxide in the retina. N.N. Osborne. Nuffield Lab of Ophthalmology, University of Oxford, Oxford, United Kingdom Nitric oxide (NO), a free radical gas with a half-life of a few seconds is implicated in various physiological and pathophysiological roles associated with the retina and its vasculature. Generated by a family of nitric oxide synthetases (NOS), NO has been shown to bind to soluble guanylyl cyclase and to mitochondrial cytochrome c oxidase to activate defined signalling cascades. Different types of NOS exist and can be activated by calcium dependent (NOS1 and NOS3) or independent (NOS2) mechanisms. Generally, NOS1 is located to neurones while NOS2 and NOS3 are in glial and endothelial cells, respectively. NO is involved in communication between different neurones, glial cells and neurones, and in the interactions of endothelial cells with pericytes and neurones. As a consequence, a reduction in the generation of endogenous NO in the healthy retina can result in vasoconstriction; the consequences of such an affect on the retina and alterations in visual processing may alter the photoreceptor transduction mechanism and communication between retinal cells. The binding of NO to mitochondrial cytochrome c oxidase to effectively compete with oxygen has been suggested be involved in a number of processes. NO-elicited events act as triggers by which mitochondrial signal transduction cascades become involved in the induction of cellular defence mechanisms and adaptive responses. Moreover, the effect of NO on the electron transport chain might lead to mitochondrial dysfunction and pathology. NO clearly has a multifaceted role in the healthy and unhealthy retina. [source]