Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of NO

  • endogenous no
  • exhaled no
  • exogenous no
  • nasal no

  • Terms modified by NO

  • no availability
  • no bioactivity
  • no bioavailability
  • no biosynthesis
  • no bond
  • no change
  • no child
  • no concentration
  • no difference
  • no donor
  • no donor sodium nitroprusside
  • no effects
  • no evidence
  • no flux
  • no formation
  • no generation
  • no inhibition
  • no level
  • no measurement
  • no metabolism
  • no metabolite
  • no molecule
  • no output
  • no overproduction
  • no oxidation
  • no pathway
  • no production
  • no ratio
  • no reduction
  • no release
  • no scavenger
  • no signal
  • no signaling
  • no significant difference
  • no synthase
  • no synthase activity
  • no synthase expression
  • no synthase inhibitor
  • no synthase inhibitor ng
  • no synthesis
  • no system
  • no treatment

  • Selected Abstracts

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

    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 (37°C) 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]

    Role of intracellular Ca2+ and calmodulin/MAP kinase kinase/extracellular signal-regulated protein kinase signalling pathway in the mitogenic and antimitogenic effect of nitric oxide in glia- and neurone-derived cell lines

    Antonella Meini
    Abstract To elucidate the mechanism of cell growth regulation by nitric oxide (NO) and the role played in it by Ca2+, we studied the relationship among intracellular Ca2+ concentration ([Ca2+]i), mitogen-activated protein kinases [extracellular signal-regulated protein kinase (ERK)] and proliferation in cell lines exposed to different levels of NO. Data showed that NO released by low [(z)-1-[2-aminiethyl]-N-[2-ammonioethyl]amino]diazen-1-ium-1,2diolate (DETA/NO) concentrations (10 µm) determined a gradual, moderate elevation in [Ca2+]i (46.8 ± 7.2% over controls) which paralleled activation of ERK and potentiation of cell division. Functionally blocking Ca2+ or inhibiting calmodulin or MAP kinase kinase activities prevented ERK activation and antagonized the mitogenic effect of NO. Experimental conditions favouring Ca2+ entry into cells led to increased [Ca2+]i (189.5 ± 4.8%), ERK activation and cell division. NO potentiated the Ca2+ elevation (358 ± 16.8%) and ERK activation leading to expression of p21Cip1 and inhibition of cell proliferation. Furthermore, functionally blocking Ca2+ down-regulated ERK activation and reversed the antiproliferative effect of NO. Both the mitogenic and antimitogenic responses induced by NO were mimicked by a cGMP analogue whereas they were completely antagonized by selective cGMP inhibitors. These results demonstrate for the first time that regulation of cell proliferation by low NO levels is cGMP dependent and occurs via the Ca2+/calmodulin/MAP kinase kinase/ERK pathway. In this effect the amplitude of Ca2+ signalling determines the specificity of the proliferative response to NO possibly by modulating the strength of ERK activation. In contrast to the low level, the high levels (50,300 µm) of DETA/NO negatively regulated cell proliferation via a Ca2+ -independent mechanism. [source]

    Downregulation of oxytocin receptors in right ventricle of rats with monocrotaline-induced pulmonary hypertension

    ACTA PHYSIOLOGICA, Issue 2 2010
    T. L. Broderick
    Abstract Aim:, Pulmonary hypertension (PH) in the rat leads to right ventricular (RV) hypertrophy, inflammation and increased natriuretic peptide (NP) levels in plasma and RV. Because the release of nitric oxide (NO) and atrial natriuretic peptide (ANP) is a function of the oxytocin receptor (OTR), we examined the effect of PH on gene and protein expression of OTR, NP (A, atrial; B, brain) and receptors (NPRs), nitric oxide synthases (NOS), interleukin (IL)-1,, IL-6 and tumour necrosis factor-, in the hypertrophied RV in a model of PH. Methods:, RV hypertrophy was induced in male Sprague,Dawley rats with monocrotaline (MCT; 60 mg kg,1) and was confirmed by the presence of an increased RV weight and RV-to-[left ventricle (LV) and septum] ratio. Results:, In the RV of MCT-treated rats, a ,40% reduction in OTR mRNA and protein was observed compared with the RV of control rats. This reduction was associated with increased transcripts of ANP and BNP in both ventricles and a corresponding increase in NP receptor mRNA expression for receptors A, B and C. Protein expression of inducible NOS was increased in the RV, whereas endothelial NOS transcripts were increased only in the LV of MCT-treated rats. In the RV of MCT-treated rats, downregulation of OTR was also associated with increased mRNA expression of IL-1, and IL-6. Conclusion:, Our results show that downregulation of the OTR in the RV of MCT-treated rats is associated with increased expression of NP and their receptors as well as IL-1, and IL-6. This reduction in OTR in RV myocardium may have an impact on cardiac function in the MCT-induced model of PH. [source]

    Nitric oxide bioavailability modulates the dynamics of microvascular oxygen exchange during recovery from contractions

    ACTA PHYSIOLOGICA, Issue 2 2010
    D. M. Hirai
    Abstract Aim:, Lowered microvascular PO2 (PO2mv) during the exercise off-transient likely impairs muscle metabolic recovery and limits the capacity to perform repetitive tasks. The current investigation explored the impact of altered nitric oxide (NO) bioavailability on PO2mv during recovery from contractions in healthy skeletal muscle. We hypothesized that increased NO bioavailability (sodium nitroprusside: SNP) would enhance PO2mv and speed its recovery kinetics while decreased NO bioavailability (l -nitro arginine methyl ester: l -NAME) would reduce PO2mv and slow its recovery kinetics. Methods:,PO2mv was measured by phosphorescence quenching during transitions (rest,1 Hz twitch-contractions for 3 min,recovery) in the spinotrapezius muscle of Sprague,Dawley rats under SNP (300 ,m), Krebs-Henseleit (Control) and l -NAME (1.5 mm) superfusion conditions. Results:, Relative to recovery in Control, SNP resulted in greater overall microvascular oxygenation as assessed by the area under the PO2mv curve (PO2 AREA; Control: 3471 ± 292 mmHg s; SNP: 4307 ± 282 mmHg s; P < 0.05) and faster off-kinetics as evidenced by the mean response time (MRToff; Control: 60.2 ± 6.9 s; SNP: 34.8 ± 5.7 s; P < 0.05), whereas l -NAME produced lower PO2 AREA (2339 ± 444 mmHg s; P < 0.05) and slower MRToff (86.6 ± 14.5 s; P < 0.05). Conclusion:, NO bioavailability plays a key role in determining the matching of O2 delivery-to-O2 uptake and thus the upstream O2 pressure driving capillary-myocyte O2 flux (i.e. PO2mv) following cessation of contractions in healthy skeletal muscle. Additionally, these data support a mechanistic link between reduced NO bioavailability and prolonged muscle metabolic recovery commonly observed in ageing and diseased populations. [source]

    Assessment of endothelial function and blood metabolite status following acute ingestion of a fructose-containing beverage

    ACTA PHYSIOLOGICA, Issue 1 2010
    A. J. Bidwell
    Abstract Aim:, Fructose intake has increased concurrent with sugar intake and this increase has been implicated in contributing to the development of metabolic syndrome risk factors. Recent evidence suggests a role for uric acid (UA) as a potential mediator via suppression of nitric oxide (NO) bioavailability. The aim of this study was to explore this hypothesis by measuring changes in UA concentration and systemic NO bioavailability as well as endothelial function in response to acute ingestion of a glucose-fructose beverage. Methods:, Ten young (26.80 ± 4.80 years), non-obese (body mass index: 25.1 ± 2.55 kg m,2; percent body fat: 13.5 ± 6.9%) male subjects ingested either a glucose (100 g dextrose in 300 mL) or isocaloric glucose-fructose (glucose : fructose; 45 : 55 g in 300 mL) beverage. Blood was sampled pre- and every 15-min post-ingestion per 90 min and assayed for glucose, lactate, fructose, total nitrate/nitrate, UA and blood lipids. Forearm blood flow and pulse-wave velocity were recorded prior to and at 30 and 45 min time intervals post-ingestion, respectively, while heart rate, systolic and diastolic blood pressure were recorded every 15 min. Results:, The glucose-fructose ingestion was associated with a significant (P < 0.05) increase in plasma lactate concentration and altered free fatty acid levels when compared with glucose-only ingestion. However, UA was not significantly different (P = 0.08) between conditions (AUC: ,1018 ± 1675 vs. 2171 ± 1270 ,mol L,1 per 90 min for glucose and glucose-fructose conditions respectively). Consequently, no significant (P < 0.05) difference in endothelial function or systemic NO bioavailability was observed. Conclusion:, Acute consumption of a fructose-containing beverage was not associated with significantly altered UA concentration, endothelial function or systemic NO bioavailability. [source]

    Combined effect of IL-17 and blockade of nitric oxide biosynthesis on haematopoiesis in mice

    ACTA PHYSIOLOGICA, Issue 1 2010
    A. Krsti
    Abstract Aim:, The study was undertaken to extend our investigation concerning both the in vivo activity of interleukin (IL)-17 and the specific role of nitric oxide (NO) in IL-17-induced effects in the process of haematopoiesis. Methods:, CBA mice were simultaneously treated with IL-17 and/or nitric oxide synthase (NOS) inhibitor, l -NAME, for 5 days and changes within various haematopoietic cell lineages in bone marrow, spleen and peripheral blood were analysed. Results:, Findings showed that administration of both IL-17 and l -NAME stimulated increase in net haematopoiesis in normal mice. IL-17-enhanced myelopoiesis was characterized by stimulation of both femoral and splenic haematopoietic progenitor cells and morphologically recognizable granulocytes. Additionally, IL-17 induced alterations in the frequency of erythroid progenitor cells in both bone marrow and spleen, accompanied with their mobilization to the peripheral blood. As a consequence of these changes in the erythroid cell compartments, significant reticulocytosis was observed, which evidenced that in IL-17-treated mice effective erythropoiesis occurred. Exposure of mice to NOS inhibitor also increased the number of both granulocyte-macrophage and erythroid progenitors in bone marrow and spleens, and these alterations were followed by the mobilization of erythroid progenitors and elevated content of reticulocytes in peripheral blood. The specific role of NO in IL-17-induced haematopoiesis was demonstrated only in the IL-17-reducing effect on bone marrow late stage erythroid progenitors, CFU-E. Conclusion:, The results demonstrated the involvement of both IL-17 and NO in the regulation of haematopoietic cell activity in various haematopoietic compartments. They further suggest that IL-17 effects are differentially mediated depending on the haematopoietic microenvironments. [source]

    Endothelin attenuates endothelium-dependent platelet inhibition in man

    ACTA PHYSIOLOGICA, Issue 4 2010
    R. E. Malmström
    Abstract Aim:, The vascular endothelium produces several substances, including nitric oxide (NO) and endothelin-1 (ET-1), which participate in the regulation of vascular tone in humans. Both these substances may exert other actions of importance for cardiovascular disease, e.g. effects on vascular smooth muscle cell proliferation and inflammation, and NO inhibits platelet function. Experiments were designed to investigate the effect of ET-1 on endothelium-dependent vasodilatation and attenuation of platelet activation. Methods:, In 25 healthy male subjects (25 ± 1 years), forearm blood flow was measured by venous occlusion plethysmography, and platelet activity was assessed by whole blood flow cytometry (platelet fibrinogen binding and P-selectin expression) in unstimulated and adenosine diphosphate (ADP)-stimulated samples during administration of ET-1, the endothelium-dependent vasodilator acetylcholine and the NO synthase inhibitor l -NMMA. Results:, Acetylcholine increased forearm blood flow and significantly inhibited platelet activation in both unstimulated and ADP-stimulated samples. In samples stimulated with 0.3 ,m ADP, fibrinogen binding decreased from 41 ± 4% to 31 ± 3% (P < 0.01, n = 11) after acetylcholine administration. The vasodilator response to acetylcholine was significantly impaired during infusions of ET-1 and l -NMMA. ET-1 did not affect platelet activity per se, whereas l -NMMA increased platelet P-selectin expression. Both ET-1 and l -NMMA attenuated the acetylcholine-induced inhibition of platelet activity. Conclusions:, Our study indicates that, further to inhibiting endothelium-dependent vasodilatation, ET-1 may also attenuate endothelium-dependent inhibition of platelet activation induced by acetylcholine. An enhanced ET-1 activity, as suggested in endothelial dysfunction, may affect endothelium-dependent platelet modulation and thereby have pathophysiological implications. [source]

    Systemic nitric oxide clamping in normal humans guided by total peripheral resistance

    ACTA PHYSIOLOGICA, Issue 2 2010
    J. A. Simonsen
    Abstract Aim:, We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels. Methods:, Normal volunteers (23,28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor NG -nitro- l -arginine methyl ester (l -NAME) at 0.5 mg kg,1 h,1. One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l -NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography. Results:,l -NAME increased MABP and total peripheral resistance (TPR, 1.02 ± 0.05 to 1.36 ± 0.07 mmHg s mL,1, mean ± SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 ± 0.05 mmHg s mL,1, P < 0.05). CO decreased with l -NAME (5.8 ± 0.3 to 4.7 ± 0.3 L min,1, P < 0.01) and returned to control when SNP was added (6.0 ± 0.3 L min,1). A decrease in plasma noradrenaline (42%, P < 0.01) during l -NAME administration was completely reversed by SNP. Plasma renin activity decreased during l -NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l -NAME and remained elevated. Conclusions:, Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation. [source]

    Enhanced pulmonary expression of the TrkB neurotrophin receptor in hypoxic rats is associated with increased acetylcholine-induced airway contractility

    ACTA PHYSIOLOGICA, Issue 3 2009
    L. K. Sciesielski
    Abstract Aim:, We have recently reported that hypoxia stimulates transcription of the TrkB neurotrophin receptor in cultured cells via stabilization of hypoxia-inducible factor-1,. Here we investigated whether the expression of TrkB and other neurotrophin receptors is oxygen-sensitive also in vivo, and explored the functional consequences of an oxygen-regulated TrkB expression. Methods:, Rats were exposed either to 21% O2 or 8% O2 for 6 h and TrkB was analysed by reverse transcription real-time PCR, in situ mRNA hybridization, and immunological techniques. The importance of the brain-derived neurotrophic factor (BDNF)-TrkB pathway in the control of mechanical airway function was assessed on isolated tracheal segments from normoxic and hypoxic rats. Results:,TrkB transcripts were increased approx. 15-fold in the lungs of hypoxic rats, and the respiratory epithelium was identified as the site of enhanced TrkB expression in hypoxia. The TrkB ligand, BDNF, significantly increased the contractile response to acetylcholine (ACh) of isolated tracheal segments from hypoxic but not from normoxic rats. This effect of BDNF was prevented by pre-incubation of the tissue specimens with the tyrosine kinase inhibitor K252a and by mechanical removal of the TrkB containing airway epithelium. Likewise, the nitric oxide (NO) synthase inhibitor l -NAME abrogated the influence of BDNF on ACh-induced contractions of isolated tracheal segments from hypoxic rats. Conclusion:, These results demonstrate that systemic hypoxia stimulates expression of the TrkB neurotrophin receptor in the airway epithelium. Furthermore, activation of TrkB signalling by BDNF in hypoxia enhances mechanical airway contractility to ACh through a mechanism that requires NO. [source]

    Role of shear stress on nitrite and NOS protein content in different size conduit arteries of swine

    ACTA PHYSIOLOGICA, Issue 2 2009
    X. Guo
    Abstract Aim:, Inherent fundamental difference exists among arteries of different sizes. The purpose of this study was to evaluate the relation between regional difference of wall shear stress (WSS) in various sizes arteries and contents of nitrite and NO synthase (NOS) isoforms. Methods:, Five different conduit arteries in a wide range of diameter (1,8 mm) were examined in the hind limbs of 13 pigs. Blood flow rate and outer diameter were measured in vivo to determine WSS. Arterial tissues were harvested for the measurement of nitrite and NOS protein contents. The concentration of nitrite, a product of NO synthesis, was determined by high-performance liquid chromatography method. Western blot analysis was used to assess the protein contents of endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS). Results:, Our data show that WSS increases with a decrease in artery diameter. Nitrite level increases with increasing WSS and hence decreases with artery diameter. The eNOS protein contents decrease with an increase in diameter. No significant difference for iNOS and nNOS protein contents was found with different artery diameter. A significant positive correlation between tissue nitrite and eNOS protein contents was also observed. Finally, the WSS-normalized eNOS is not significantly different in various size vessels. Conclusion:, Regional difference in blood flow has no effect on iNOS and nNOS protein contents in these conduit arteries. Regional difference in eNOS expression and nitrite contents may be related to the WSS-induced NO by the endothelium under normal physiological conditions. [source]

    Adenosine infusion attenuates soluble RAGE in endotoxin-induced inflammation in human volunteers

    ACTA PHYSIOLOGICA, Issue 1 2009
    A. Soop
    Abstract Aim:, To evaluate possible anti-inflammatory effects of pre-treatment with adenosine in a human experimental inflammatory model. Methods:, The study design was double-blind, crossover, placebo-controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.5 h with infusions of adenosine 40 ,g kg,1 min,1 or placebo. Thirty minutes after the start of adenosine or placebo, 2 ng kg,1E-Coli endotoxin was administered. Heart rate, body temperature, blood pressure, plasma cytokines (TNF-,, IL-6 and IL-10), soluble RAGE and resistin, exhaled nitric oxide and nitrite/nitrate in urine were determined. Results:, Endotoxin elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever) and led to prominent release of the cytokines studied (P < 0.001). Resistin in plasma increased after endotoxin (P < 0.001). After placebo treatment, soluble RAGE (sRAGE) in plasma increased 5 h after the endotoxin challenge (P < 0.001) but not after adenosine. After placebo, orally exhaled NO increased with a peak at 4 h (P < 0.001), although there was no statistically significant difference between the two treatments. Nitrite/nitrate in urine (n = 11) did not differ between adenosine and placebo treatments. Conclusion:, In conclusion, adenosine infusion starting before endotoxin challenge in humans attenuated sRAGE significantly but otherwise had no clear anti-inflammatory effect. Adenosine as a potential anti-inflammatory treatment in humans needs further study, including use of higher doses. The mechanism underlying the effect of adenosines on sRAGE remains unknown. [source]

    B2 kinin receptors mediate the Indian red scorpion venom-induced augmentation of visceral reflexes via the nitric oxide cyclic guanosine monophosphate pathway

    ACTA PHYSIOLOGICA, Issue 4 2009
    S. Kanoo
    Abstract Aim:, This study was performed to delineate the kinin (receptor)-dependent pathways in the Indian red scorpion (Mesobuthus tamulus; MBT) venom-induced pulmonary oedema as well as the augmentation of cardio-pulmonary reflexes evoked by phenyldiguanide (PDG). Methods:, In urethane-anaesthetized adult rats, the effect of venom on the PDG reflex responses (blood pressure, heart rate and respiration rate) and the pulmonary water content was ascertained using various antagonists(des- Arg, B1 receptor antagonist; Hoe 140, B2 receptor antagonist; N, -nitro- l -arginine methyl ester (l -NAME), nitric oxide (NO) synthase inhibitor; methylene blue, soluble guanylate cyclase inhibitor; and glibenclamide, K+ATP channel blocker). The effect of phosphodiesterase V inhibitor (sildenafil citrate) on the reflex response and the pulmonary water content was also examined and compared with venom-induced responses. Results:, Intravenous injection of PDG (10 ,g kg,1) evoked apnoea, bradycardia and hypotension lasting >60 s. Exposure to MBT venom (100 ,g kg,1) for 30 min augmented the PDG reflex responses by two times and increased the pulmonary water content, significantly. Hoe 140 blocked the venom-induced responses (augmentation of PDG reflex and increased pulmonary water content) whereas des-Arg did not. l -NAME, methylene blue or glibenclamide also blocked the venom-induced responses. Furthermore, sildenafil citrate (that increases cGMP levels) produced augmentation of PDG reflex response and increased the pulmonary water content as seen with venom. Conclusion:, The results indicate that venom-induced responses involve B2 kinin receptors via the NO-dependent guanylate cyclase-cGMP pathway involving K+ATP channels. [source]

    Imidazoline-induced amplification of glucose- and carbachol-stimulated insulin release includes a marked suppression of islet nitric oxide generation in the mouse

    ACTA PHYSIOLOGICA, Issue 3 2009
    S. Meidute-Abaraviciene
    Abstract Aim:, The role of islet nitric oxide (NO) production in insulin-releasing mechanisms is unclear. We examined whether the beneficial effects of the imidazoline derivative RX 871024 (RX) on ,-cell function might be related to perturbations of islet NO production. Methods:, Experiments were performed with isolated islets or intact mice challenged with glucose or carbachol with or without RX treatment. Insulin was determined with radioimmunoassay, NO generation with high-performance liquid chromatography and expression of inducible NO synthase (iNOS) with confocal microscopy. Results:, RX treatment, in doses lacking effects on basal insulin, greatly amplified insulin release stimulated by the NO-generating secretagogues glucose and carbachol both in vitro and in vivo. RX also improved the glucose tolerance curve. Islets incubated at high glucose levels (20 mmol L,1) displayed increased NO production derived from both neuronal constitutive NO synthase (ncNOS) and iNOS. RX abrogated this glucose-induced NO production concomitant with amplification of insulin release. Confocal microscopy revealed abundant iNOS expression in , cells after incubation of islets at high but not low glucose levels. This was abolished after RX treatment. Similarly, islets cultured for 24 h at high glucose levels showed intense iNOS expression in , cells. This was abrogated with RX and followed by an amplified glucose-induced insulin release. Conclusion:, RX effectively counteracts the negative impact of ,-cell NO generation on insulin release stimulated by glucose and carbachol suggesting imidazoline compounds by virtue of NOS inhibitory properties being of potential therapeutic value for treatment of ,-cell dysfunction in hyperglycaemia and type 2 diabetes. [source]

    EndothelinA (ETA) and ETB receptor-mediated regulation of nitric oxide synthase 1 (NOS1) and NOS3 isoforms in the renal inner medulla

    ACTA PHYSIOLOGICA, Issue 4 2007
    J. C. Sullivan
    Abstract Aim:, Our laboratory and others have shown that endothelin (ET)-1 directly stimulates nitric oxide (NO) production in inner medullary collecting duct (IMCD) cells. The goal of this study was to determine which NO synthase (NOS) isoforms in IMCD are sensitive to ET-1, and the role of ETA and ETB receptor activation in vivo and in vitro. Methods:, NOS enzymatic activity and NOS isoform protein expression were examined in cultured IMCD-3 cells and isolated renal inner medulla. ETB receptor-deficient homozygous rats (sl/sl) have elevated levels of circulating ET-1 and lack a functional ETB signalling pathway in kidneys, and furthermore provides a unique model to study ETA receptor signalling in the renal inner medulla in vivo. Results:, Incubation of IMCD-3 cells with exogenous ET-1 (50 nm) resulted in ETA -dependent increased NOS1 protein expression in IMCD-3 cells with no effect on NOS2 or NOS3 expression. ETB receptor antagonism has no effect on NOS expression in IMCD-3 cells. Consistent with in vitro results, cytosolic NOS1 protein expression was significantly greater in the renal inner medulla of sl/sl rats compared with heterozygous (sl/+) controls, with no alteration in NOS3 expression. In contrast to protein expression data, NOS1- and NOS3-specific enzymatic activities decreased in the cytosolic fraction from the renal inner medulla of sl/sl compared with sl/+. Conclusion:, These results provide evidence that both ETA and ETB receptors regulate NOS isoform activity in the renal inner medulla and specifically support the hypothesis that ETA receptor activation increases NOS1 expression. [source]

    Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L -arginine and antioxidants

    ACTA PHYSIOLOGICA, Issue 4 2007
    M. P. Koeners
    Abstract Aim:, Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. Methods:, Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. N, -nitro- l -arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). Results:, Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 ± 4 vs. 33 ± 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 ± 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. Conclusion:, Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation. [source]

    Nitric oxide counteracts angiotensin II induced contraction in efferent arterioles in mice

    ACTA PHYSIOLOGICA, Issue 4 2004
    A. Patzak
    Abstract Aim:, Efferent arterioles (Ef) are one of the final control elements in glomerular haemodynamics. The influence of nitric oxide (NO) on Ef remains ambiguous. Methods:, To test the hypothesis that endothelial NO plays an important role in this context, afferent arterioles (Af) and Ef of wild-type mice (WT), and Ef of mice lacking the endothelial NO synthetase [eNOS(,/,)] were perfused. Perfusion was performed in Ef via Af (orthograde) as well as from the distal end of Ef (retrograde), which provides an estimate for the importance of substances derived from the glomerulus. Angiotensin II (Ang II) was added in doses ranging from 10,12 to 10,6 mol L,1 to the bath solution. Results:, Ang II reduced the luminal diameter of Af to 68 ± 7 and in Ef to 55 ± 8% during orthograde, and to 35 ± 6% during retrograde perfusion (10,6 mol L,1 Ang II) in WT. Pre-treatment with NG -Nitro- l -arginine-methylester (l -NAME) (10,4 mol L,1) increased the Ang II sensitivity in retrograde (17 ± 9%) and orthograde perfused Ef (19 ± 9%). The Ang II sensitivity was enhanced in eNOS(,/,) mice compared with WT, too. Already at a dose of Ang II 10,9 mol L,1, luminal diameters diminished to 8 ± 7 and 7 ± 4%. Conclusion:, The increased Ang II sensitivity during l -NAME pre-treatment and in eNOS(,/,) mice indicates a strong counteraction of endothelial derived NO on Ang II induced contraction in Ef. Moreover, Ef are similarly sensitive to Ang II during either retrograde or orthograde perfusion in the absence of NO effects, suggesting that NO mediates, at least in part, the action of potential vasodilatory substances from the glomerulus. [source]

    Responses of the bronchial and pulmonary circulations to short-term nitric oxide inhalation before and after endotoxaemia in the pig

    ACTA PHYSIOLOGICA, Issue 1 2002
    R. J. M. Middelveld
    ABSTRACT The physiological responses of the bronchial circulation to acute lung injury and endotoxin shock are largely unexplored territory. This study was carried out to study the responsiveness of the bronchial circulation to nitric oxide (NO) inhalation before and after endotoxaemia, in comparison with the pulmonary circulation, as well as to study changes in bronchial blood flow during endotoxaemia. Six anaesthetized pigs (pre-treated with the cortisol-synthesis inhibitor metyrapone) received an infusion of 10 µg/kg endotoxin during 2 h. Absolute bronchial blood flow was measured via an ultrasonic flow probe around the bronchial artery. The pigs received increasing doses of inhaled NO over 5 min each (0, 0.2, 2 and 20 ppm) before and after 4 h of endotoxaemia. The increase in bronchial vascular conductance during 5 min of inhalation of 20 ppm NO before endotoxin shock was significantly higher (area under curve (AUC) 474.2 ± 84.5% change) than after endotoxin shock (AUC 118.2 ± 40.4%, P < 0.05 Mann,Whitney U -test). The reduction of the pulmonary arterial pressure by 20 ppm NO was not different. A short rebound effect of the pulmonary arterial pressure occurred after discontinuation of inhaled NO before endotoxaemia (AUC values above baseline 54.4 ± 19.7% change), and was virtually abolished after endotoxaemia (AUC 6.1 ± 4.0%, P = 0.052, Mann,Whitney U -test). Our results indicate that the responsiveness of the bronchial circulation to inhalation of increasing doses of inhaled NO during endotoxin shock clearly differ from the responsiveness of the pulmonary circulation. The reduced responsiveness of the bronchial circulation is probably related to decreased driving pressure for the bronchial blood flow. The absence of the short rebound effect on pulmonary arterial pressure (PAP) after induction of shock could be related to maximum constriction of the pulmonary vessels at 4 h. [source]

    Nerve growth factor increases airway responses and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea-pig model

    ACTA PHYSIOLOGICA, Issue 2 2001
    S. G. Friberg
    There is a growing body of evidence supporting the idea that nerve growth factor (NGF) may be involved in the development of asthma-associated symptoms, such as airway hyper-responsiveness. Increased levels of NGF have recently been described in serum and in the airways of asthmatics. We have examined whether exhaled nitric oxide (NO) levels might be altered during the increased airway responses upon NGF treatment in guinea-pigs in vivo. Intravenous (i.v.) administration of histamine normally elicits a rapid peak in insufflation pressure (IP) and in exhaled NO, followed by a period of decreased concentrations of exhaled NO. Anaesthetized guinea-pigs were pre-treated intravenously with either saline, 4 or 80 ng kg,1 NGF 30 min before i.v. challenge with 16 ,g kg,1 histamine. At 80 ng kg,1 NGF significantly enhanced the airway obstruction caused by histamine, whereas the peak acute increase in exhaled NO was not enhanced. Following the increase, came a rapid drop, an effect enforced in the NGF treated animals. Subsequently, the time to return to 90% of resting exhaled NO was increased, from 12 min in saline-treated animals to 48 min in NGF-treated animals. Our data confirm that NGF can enhance airway responses to histamine. Moreover, our study shows a decrease in exhaled NO following a histamine challenge, an effect enhanced by NGF. A reduced ability to release exhaled NO may be a mechanism for increased airway responses during elevated NGF levels. The interaction between NGF and airway NO formation, and its relation to airway responses, merit further investigation. [source]

    Expression of zebrafish nos2b surrounds oral cavity

    Kar-Lai Poon
    Abstract Inducible nitric oxide synthase (NOS2) catalyzes the production of nitric oxide (NO), and is one of the factors establishing innate immunity. In zebrafish, Nos2 is represented by nos2a and nos2b. Here, we report the cloning and expression pattern of the zebrafish nos2b gene, which does not seem to participate in induced immune response. nos2b was mapped to zebrafish linkage group 15. The spatial and temporal expression pattern of nos2b in embryonic zebrafish was analyzed by whole-mount in situ hybridization. nos2b is expressed constitutively in two primordia located along the ventral midline. The first group of cells contributes to the neurohypophysis. Initially at the level of the ventral hindbrain, the second group of cells migrates closely with the thyroid primordium to its final position at the basihyal by 3 dpf. Thus, the analysis of expression pattern of nos2b reveals complex morphogenetic movements resulting in its expression surrounding the oral cavity. Developmental Dynamics 237:1662,1667, 2008. © 2008 Wiley-Liss, Inc. [source]

    Nitric oxide regulates axonal regeneration in an insect embryonic CNS

    Michael Stern
    Abstract In higher vertebrates, the central nervous system (CNS) is unable to regenerate after injury, at least partially because of growth-inhibiting factors. Invertebrates lack many of these negative regulators, allowing us to study the positive factors in isolation. One possible molecular player in neuronal regeneration is the nitric oxide (NO),cyclic guanosine-monophosphate (cGMP) transduction pathway which is known to regulate axonal growth and neural migration. Here, we present an experimental model in which we study the effect of NO on CNS regeneration in flat-fillet locust embryo preparations in culture after crushing the connectives between abdominal ganglia. Using whole-mount immunofluorescence, we examine the morphology of identified serotonergic neurons, which send a total of four axons through these connectives. After injury, these axons grow out again and reach the neighboring ganglion within 4 days in culture. We quantify the number of regenerating axons within this period and test the effect of drugs that interfere with NO action. Application of exogenous NO or cGMP promotes axonal regeneration, whereas scavenging NO or inhibition of soluble guanylyl cyclase delays regeneration, an effect that can be rescued by application of external cGMP. NO-induced cGMP immunostaining confirms the serotonergic neurons as direct targets for NO. Putative sources of NO are resolved using the NADPH-diaphorase technique. We conclude that NO/cGMP promotes outgrowth of regenerating axons in an insect embryo, and that such embryo-culture systems are useful tools for studying CNS regeneration. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source]

    Endothelially Derived Nitric Oxide Affects the Severity of Early Acetaminophen-induced Hepatic Injury in Mice

    Steven D. Salhanick MD
    Abstract Objectives: The precise mechanism of hepatocellular toxicity following acetaminophen (APAP) poisoning remains unclear. Nitric oxide is implicated in APAP toxicity as an inflammatory signaling molecule and as a precursor to the free radical peroxynitrate. The effects of inducible nitric oxide synthase (iNOS)-derived NO in APAP toxicity are known; however, the role of endothelial nitric oxide synthase (eNOS)-derived NO is unknown. The authors sought to evaluate the effect of eNOS-derived NO during APAP toxicity. Methods: C57BL6/J mice deficient in eNOS (eNOS KO) or iNOS (iNOS KO) and wild-type mice (WT) were treated with 300 mg/kg APAP. Alanine aminotransferase levels and plasma nitrate and nitrite levels were measured. Hypoxia inducible factor (HIF)-1, and Glucose Transporter 1 (Glut-1) levels were determined by Western blot. Results: Alanine aminotransferase levels were significantly elevated in all treated animals. Alanine aminotransferase levels were significantly lower in eNOS KO and iNOS KO than in treated WT animals. Plasma nitrate/nitrite levels were significantly higher in WT animals than in iNOS KO and eNOS KO animals. HIF-1, expression was increased in WT mice and decreased in iNOS KO mice. Glut-1 is a downstream, indirect marker of HIF function. Glut-1 expression was increased in WT and eNOS KO mice. Conclusions: Deficiency of either iNOS or eNOS results in decreased NO production and is associated with reduced hepatocellular injury following APAP poisoning. HIF-1, and Glut-1 levels are increased following APAP poisoning, implying that HIF-1, is functional during the pathogenic response to APAP poisoning. [source]

    The effects of lipid-lowering drug therapy on cardiovascular responsiveness in type 2 diabetic patients

    Laurence Guy HowesArticle first published online: 18 MAR 200
    Type 2 diabetes is associated with a high prevalence of dyslipidaemia and a high incidence of cardiovascular disease. Lipid lowering therapy with HMG Co-A reductase inhibitors (statins) reduce the risk of cardiovascular events in type 2 diabetic and non-diabetic patients, effects which are believed to be partly due to improvements in vascular function. The aetiology of abnormal vascular function in type 2 diabetics is likely to be multifactorial and the pattern of vascular dysfunction in type 2 diabetes may differ from that which occurs in non-diabetic patients with dyslipidaemia. Abnormalities in endothelium derived hyperpolarising factor (EDHF) mediated vasodilation in resistance vessels may be more prominent in both type 1 and type 2 diabetes than in non-diabetic patients with endothelial dysfunction. The effects of lipid lowering therapy on vascular responsiveness may differ in type 2 diabetic patients from those found in non-diabetic patients. Statin therapy does not appear to improve responses to endothelial dependent vasodilators in type 2 diabetics, but may alter the ratio between nitric oxide (NO) and EDHF mediated responses. Fibrate therapy improves flow mediated dilation of brachial arteries in type 2 diabetic patients, but only appears to improve endothelium dependant vasodilator responses in resistance vessels when given in conjunction with co-enzyme Q. [source]

    Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases

    Eugenio Cersosimo
    Abstract Cardiovascular disease affects approximately 60% of the adult population over the age of 65 and represents the number one cause of death in the United States. Coronary atherosclerosis is responsible for the vast majority of the cardiovascular events, and a number of cardiovascular risk factors have been identified. In recent years, it has become clear that insulin resistance and endothelial dysfunction play a central role in the pathogenesis of atherosclerosis. Much evidence supports the presence of insulin resistance as the fundamental pathophysiologic disturbance responsible for the cluster of metabolic and cardiovascular disorders, known collectively as the metabolic syndrome. Endothelial dysfunction is an important component of the metabolic or insulin resistance syndrome and this is demonstrated by inadequate vasodilation and/or paradoxical vasoconstriction in coronary and peripheral arteries in response to stimuli that release nitric oxide (NO). Deficiency of endothelial-derived NO is believed to be the primary defect that links insulin resistance and endothelial dysfunction. NO deficiency results from decreased synthesis and/or release, in combination with exaggerated consumption in tissues by high levels of reactive oxygen (ROS) and nitrogen (RNS) species, which are produced by cellular disturbances in glucose and lipid metabolism. Endothelial dysfunction contributes to impaired insulin action, by altering the transcapillary passage of insulin to target tissues. Reduced expansion of the capillary network, with attenuation of microcirculatory blood flow to metabolically active tissues, contributes to the impairment of insulin-stimulated glucose and lipid metabolism. This establishes a reverberating negative feedback cycle in which progressive endothelial dysfunction and disturbances in glucose and lipid metabolism develop secondary to the insulin resistance. Vascular damage, which results from lipid deposition and oxidative stress to the vessel wall, triggers an inflammatory reaction, and the release of chemoattractants and cytokines worsens the insulin resistance and endothelial dysfunction. From the clinical standpoint, much experimental evidence supports the concept that therapies that improve insulin resistance and endothelial dysfunction reduce cardiovascular morbidity and mortality. Moreover, interventional strategies that reduce insulin resistance ameliorate endothelial dysfunction, while interventions that improve tissue sensitivity to insulin enhance vascular endothelial function. There is general agreement that aggressive therapy aimed simultaneously at improving insulin-mediated glucose/lipid metabolism and endothelial dysfunction represents an important strategy in preventing/delaying the appearance of atherosclerosis. Interventions that 1 correct carbohydrate and lipid metabolism, 2 improve insulin resistance, 3 reduce blood pressure and restore vascular reactivity, and 4 attenuate procoagulant and inflammatory responses in adults with a high risk of developing cardiovascular disease reduce cardiovascular morbidity and mortality. Whether these benefits hold when the same prevention strategies are applied to younger, high-risk individuals remains to be determined. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    Beneficial effects of aminoguanidine on the cardiovascular system of diabetic rats

    Krisztián Stadler
    Abstract Background The study focused on investigating the effect of aminoguanidine on cardiovascular damages in diabetes and the possible mechanisms of its action. Methods Aminoguanidine (AMNG) was used to treat streptozotocin-induced diabetic rats, and the effects were compared to those obtained under insulin treatment. Blood metabolic parameters, ,NO and ONOO, as well as protein carbonyl levels and cardiac hypertrophy were determined. Results Diabetic animals showed increased ,NO levels and markedly increased ONOO, generation in the aorta, along with a significant hypertrophy and protein carbonylation in the cardiac tissue. Both AMNG and insulin treatment suppressed the levels of overproduced ,NO or ONOO, in the vasculature, but only AMNG was able to prevent hypertrophic alterations and reduce protein carbonylation in the cardiac tissue. Conclusions Oxidative protein modification, together with cardiac hypertrophy and high generation of ,NO and ONOO,, are important early events in the development of cardiovascular complications in diabetes. Aminoguanidine could prevent hypertrophy through inhibition of production of nonenzymatic glycation products rather than via inhibition of ,NO production. Copyright © 2004 John Wiley & Sons, Ltd. [source]

    Adrenomedullin and diabetes mellitus

    Eva Ruzicska
    Abstract Adrenomedullin (AM) is a novel 52 amino acid peptide hormone, originally isolated from human pheochromocytoma. AM acts as a local autocrine and/or paracrine vasoactive hormone and has vasodilator and blood pressure lowering properties. AM as a vasodilative molecule protects the vascular wall but its exact role is still uncertain. AM is considered to play an important endocrine role in various tissues in maintaining electrolyte and fluid homeostasis. Its plasma concentration in healthy conditions is low. In hypertension, chronic renal failure and congestive heart failure its plasma concentration increases in a parallel manner with the severity of the disease. It is assumed that this peptide plays an important role in physiological and pathological conditions compensating the effects of vasoconstrictive molecules. Investigations have proven that in diabetic angiopathies the levels and production of vasoconstrictive factors and AM are increased, while other relaxing substances such as nitric oxide (NO) are decreased. It is still uncertain whether the increased release of AM is a compensatory mechanism or a coincidental event. Although the precise role of AM in the pathogenesis of diabetic complications is still to be elucidated, the altered concentration of AM in diabetes could indicate a certain interaction between AM induction and vascular function. Hence, the induction of vascular AM can be a new target of therapeutic approach to diabetic complications. Copyright © 2001 John Wiley & Sons, Ltd. [source]

    Effects of diabetes on plasma nitrotyrosine levels

    DIABETIC MEDICINE, Issue 6 2004
    X. L. Wang
    Abstract Background Oxidative stress plays a major role in disease processes such as atherosclerosis and diabetes. Peroxynitrite is a reaction product of nitric oxide (NO) and superoxide and a potent oxidant. The peroxynitrite-mediated tyrosine nitration, which forms nitrotyrosine (NT), is associated with several pathological conditions. Methods We measured plasma NT levels using the HPLC method in 40 Mexican Americans with diabetes, but not taking medications, and 40 age- and sex-matched euglycaemic controls. Results Plasma-free NT levels were not different between subjects with diabetes (11.0 ± 1.7 nmol/l, n = 40) and with non-diabetes (10.4 ± 1.5 nmol/l, n = 40). There was also no association with levels of fasting glucose (r = ,0.049, P = 0.663) or 2-h glucose (r = ,0.099, P = 0.390). However, females had significantly lower free NT level (7.6 ± 1.4 nmol/l, n = 40) than males (13.8 ± 1.7 nmol/l, n = 40, P = 0.005), which were not affected by age, smoking status, BMI and glucose levels. Conclusions In contrast to some earlier reports, our study shows that diabetes has no effect on plasma NT levels in Mexican Americans. We have also demonstrated lower free NT levels in females than males, which may partly explain the lower risk profile to vascular disease in women. [source]

    Gestational diabetes affects platelet behaviour through modified oxidative radical metabolism

    DIABETIC MEDICINE, Issue 1 2004
    L. Mazzanti
    Abstract Aims Patients with Type 1 and Type 2 diabetes mellitus show altered platelet function including decreased nitric oxide synthase (NOS) activity and increased peroxynitrite production. Gestational diabetes mellitus (GDM) is a clinical condition which is ideal for evaluating short-term effects of impaired glucose metabolism, ruling out the possibility that the platelet abnormalities are a consequence of diabetic complications. The aim of the present work was to study NO metabolism in platelets from pregnant women with GDM. The production of peroxides was also studied as it is strongly involved in peroxynitrite formation. Methods Platelet NOS activity and peroxynitrite production, levels of hydroperoxides and thiobarbituric acid reactive substances (TBARS) in platelet membranes in the basal state and after in vitro peroxidative stress with phenylhydrazine were determined in 40 pregnant women with GDM, 40 healthy pregnant women (pregnant controls) of comparable age and gestational age, and 15 healthy non-pregnant women (controls). Results NOS activity was significantly increased in both groups of pregnant women compared with non-pregnant ones, and in GDM women compared with pregnant controls. Production of peroxynitrite was higher in GDM women than in pregnant controls, who also had significantly reduced production compared with non-pregnant women. Basal levels of peroxidation of the platelet membranes evaluated either by hydroperoxide content and TBARS levels or the susceptibility to peroxidation were increased in GDM patients in comparison with both control groups. Conclusions We have shown a modification in platelet NO and peroxynitrite production and an increase in platelet indicators of oxidative stress in GDM women compared with healthy pregnant women which might be at the basis of a cellular dysfunction. [source]

    Evidence for a widespread involvement of NO in control of photogenesis in bioluminescent fish

    ACTA ZOOLOGICA, Issue 4 2010
    Jenny Krönström
    Abstract Krönström, J. and Mallefet, J. 2009. Evidence for a widespread involvement of NO in control of photogenesis in bioluminescent fish. ,Acta Zoologica (Stockholm) 91: 474,483. The presence of nitric oxide synthase (NOS) and nerve fibres in the photophores of seven bioluminescent fish species (Hygophum benoiti, Myctophum punctatum, Electrona risso, Cyclothone braueri, Vinciguerria attenuata, Maurolicus muelleri and Porichthys notatus) with endogenous photocytes, were investigated. Antibodies directed against neuronal and inducible NOS (n and iNOS respectively) and NADPH-diaphorase activity were used to reveal the locations of NOS, while antibodies directed against acetylated tubulin were used to visualize nerve fibres. The nNOS antibody labelled structures in all investigated photophores except in the organs from P. notatus. The photocytes of P. notatus showed NADPH-diaphorase activity. In the myctophid species, NOS-like immunoreactivity was found in small intracellular structures of the photocytes and in nerve fibres reaching the photocytes. nNOS-positive fibres were also found among lens/filter cells in V. attenuata, and in M. muelleri the cytoplasm of lens/filter cells contained NOS-like material. In C. braueri, a cell type located at a collecting chamber for luminous products in the photophore contained NOS-like material. All photophores received an innervation reaching the photocytes, as well as other components including lens/filter areas. The results of this study comply with an involvement of nitric oxide in the control of bioluminescence in several fish species. [source]

    Effects of a new 1,3,4-thiadiazolium mesoionic compound, MI-D, on the acute inflammatory response

    Júlio C. Cardoso
    Abstract A new mesoionic compound, 4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine (MI-D), is described along with some of its biological properties. Its effects on hepatic metabolism, on O and nitric oxide (NO) production, and in in vivo models for potential antinociceptive, antipyretic, and antiinflammatory activities were determined. In perfused rat liver, MI-D (25 µM) stimulated glycogenolysis (95%), and inhibited oxygen uptake (37%) with affecting glycolysis. In phorbol 12-myristate 13-acetate-stimulated macrophages, O generation was reduced (95%) by MI-D (15 µM), whereas the production of NO was unaffected. MI-D (2 mg/kg) inhibited (55%) the number of abdominal writhings induced by acetic acid. At 1 mg/kg, MI-D inhibited the febrile response (5 h) induced by lipopolysaccharide (LPS) and was also effective against a preexisting febrile response. Treatment with MI-D (1 mg/kg) reduced by 67% prostaglandin (PGE2) levels in the cerebrospinal fluid of LPS-exposed mice, and at a higher dose (8 mg/kg) MI-D inhibited paw edema formation (2 h) induced by carrageenan. MI-D has a spectrum of activities similar to other nonsteroidal antiinflammatory drugs, qualifying it as a potential anti-inflammatory drug. Drug Dev. Res. 61:207,217, 2004. © 2004 Wiley-Liss, Inc. [source]

    Thaliporphine protects ischemic and ischemic-reperfused rat hearts via an NO-dependent mechanism

    Li-Man Hung
    Abstract In ischemia or ischemia-reperfusion (I/R), nitric oxide (NO) can potentially exert several beneficial effects. Thaliporphine, a natural alkaloid with Ca2+ channel-activating and Na+/K+ channel-blocking activities, increased NO levels and exerted cardioprotective action in ischemic or I/R rats. The role of NO in the cardioprotective actions of thaliporphine was assessed. The severity of rhythm disturbances and mortality in anesthetized rats with either coronary artery occlusion for 30 min, or 5 min followed by 30-min reperfusion, were monitored and compared in thaliporphine- vs. placebo-treated groups. Thaliporphine treatment significantly increased NO and decreased lactate dehydrogenase (LDH) levels in the blood during the end period of ischemia or I/R. These changes in NO and LDH levels by thaliporphine were associated with a reduction in the incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during ischemic or I/R period. The mortality of animals was also completely prevented by 1 × 10,8 moles/kg of thaliporphine. In animals subjected to 4 h of left coronary artery occlusion, 1 × 10,7 moles/kg of thaliporphine dramatic reduced cardiac infarct zone from 46 ± 6% to 7.1 ± 1.9%. Inhibition of NO synthesis with 3.7 × 10,6 moles/kg of N, -nitro-L-arginine methyl ester (L-NAME) abolished the beneficial effects of thaliporphine during 30 min or 4 h myocardial ischemia. However, the antiarrhythmic activity and mortality reduction efficacy of thaliporphine during reperfusion after 5 min of ischemia was only partially antagonized by L-NAME. These results showed that thaliporphine efficiently exerted the cardioprotections either in acute or prolonged coronary artery occlusion or occlusion-reperfusion situations. The fact that thaliporphine induced cardioprotective effects were abrogated by L-NAME indicates that NO is an important mediator for the cardioprotective effects of thaliporphine in acute or prolonged ischemia, whereas antioxidant activities may contribute to the protection of I/R injury. Drug Dev. Res. 52:446,453, 2001. © 2001 Wiley-Liss, Inc. [source]