scholarly journals Superoxide dismutase restores the influence of nitric oxide on renal arterioles in diabetes mellitus.

1995 ◽  
Vol 5 (8) ◽  
pp. 1559-1566
Author(s):  
K Ohishi ◽  
P K Carmines
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Superoxide Dismutase ◽  
Early Stage ◽  
Dependent Manner ◽  
Superoxide Anions ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Concentration Dependent Manner ◽  
Arteriolar Diameter

Experiments were performed to determine the influence of endogenous nitric oxide (NO) on basal arteriolar diameter in kidneys from diabetic rats and to evaluate the role of superoxide anions as modulators of NO activity under these conditions. Male Sprague-Dawley rats were injected with streptozotocin (STZ, 65 mg/kg i.v.) and received insulin via ip osmotic minipumps (3 U/kg per day). Sham rats received vehicle treatments. Videomicroscopy was used, in conjunction with the in vitro blood-perfused juxtamedullary nephron technique, to visualize renal afferent and efferent arterioles 2 wk after the onset of diabetes. Baseline afferent arteriolar inside diameter was greater in STZ (32 +/- 2 microns) than in sham rats (24 +/- 2 microns). Efferent arteriolar diameter did not differ between STZ (24 +/- 2 microns) and sham rats (21 +/- 1 microns). In kidneys from sham rats, N omega-nitro-L-arginine (L-NNA, an NO synthase inhibitor) decreased arteriolar diameters in a concentration-dependent manner, with 100 microM L-NNA significantly reducing both afferent (13 +/- 2%) and efferent (11 +/- 1%) diameters. In kidneys from STZ rats, 100 microM L-NNA reduced afferent and efferent diameters by only 3 +/- 1 and 4 +/- 1%, respectively, indicating a suppressed arteriolar influence of NO. In STZ kidneys treated with superoxide dismutase (SOD, 150 U/mL), afferent and efferent arteriolar L-NNA responses were restored to levels comparable to those of SOD-treated and untreated sham kidneys. These observations suggest that suppressed SOD activity reduces the tonic influence of NO on renal arterioles during the early stage of diabetes mellitus, perhaps through allowing the accumulation of NO-scavenging superoxide anions.

Endothelium-derived microparticles impair endothelial function in vitro

2004 ◽  
Vol 286 (5) ◽  
pp. H1910-H1915 ◽  
Author(s):  
Sergey V. Brodsky ◽  
Fan Zhang ◽  
Alberto Nasjletti ◽  
Michael S. Goligorsky
Keyword(s):  
Nitric Oxide ◽  
Surrogate Marker ◽  
Common Denominator ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Concentration Dependent Manner ◽  
Endothelial Microparticles ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor

Endothelial cell dysfunction (ECD) is emerging as the common denominator for diverse and highly prevalent cardiovascular diseases. Recently, an increased number of procoagulant circulating endothelial microparticles (EMPs) has been identified in patients with acute myocardial ischemia, preeclampsia, and diabetes, which suggests that these particles represent a surrogate marker of ECD. Our previous studies showed procoagulant potential of endothelial microparticles and mobilization of microparticles by PAI-1. The aim of this study was to test the effects of isolated EMPs on the vascular endothelium. EMPs impaired ACh-induced vasorelaxation and nitric oxide production by aortic rings obtained from Sprague-Dawley rats in a concentration-dependent manner. This effect was accompanied by increased superoxide production by aortic rings and cultured endothelial cells that were coincubated with EMPs and was inhibited by a SOD mimetic and blunted by an endothelial nitric oxide synthase inhibitor. Superoxide was also produced by isolated EMP. In addition, p22(phox) subunit of NADPH-oxidase was detected in EMP. Our data strongly suggest that circulating EMPs directly affect the endothelium and thus not only act as a marker for ECD but also aggravate preexisting ECD.

The Response of Antioxidant Enzyme and ATPase in Bacteria Exposed to 1,2-dichlorobenzene

2013 ◽  
Vol 807-809 ◽  
pp. 680-683 ◽  
Author(s):  
Hui Xing Liang ◽  
Ai Hui Chen ◽  
Cheng Ding ◽  
Zhao Xia Li
Keyword(s):  
Oxidative Stress ◽  
Escherichia Coli ◽  
Superoxide Dismutase ◽  
Dependent Manner ◽  
Bacterial Strains ◽  
Sod Activity ◽  
Concentration Dependent Manner ◽  
E Coli ◽  
Short Period ◽  
Stimulation Of

The activity response of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), ATP enzyme activities of Escherichia coli Q8, Bacillus subtilis L11, and Bacillus cereus OL-1 following exposure to 1,2-dichlorobenzene (1,2-DCB) was investigated. The bacterial strains were treated with the different concentrations of 1,2-DCB. Results obtained indicated that SOD and CAT activities in the tested bacteria increased significantly in a concentration-dependent manner after different concentrations of 1,2-DCB were applied. The activity of SOD in B. subtilis was stimulated and reached the highest level after treatment with 10 mg/L 1,2-DCB for 3 h. For B.cereus OL-1, there was another stimulation of SOD activity after 1,2-DCB application for about 5 h The stimulation by 1,2-DCB showed a relative lag for E. coli. 1,2-DCB had an evident influence on ATPase activity in the three bacteria within a relatively short period. 1,2-DCB would have caused a certain oxidative stress on the three bacteria which may not only elevate SOD and CAT activities but also generate new SOD isozymes to antagonize oxidative stress. All indirectly reflect the existence of poisonous and harmful material in the environment , and can indicate the influence of pollution sensitivily. Therefore SOD, CAT and ATP enzyme activity in microbial body can be regarded as a molecular index of polluting ,which is feasible.

Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes

1998 ◽  
Vol 274 (1) ◽  
pp. C245-C252 ◽  
Author(s):  
Junsuke Igarashi ◽  
Masashi Nishida ◽  
Shiro Hoshida ◽  
Nobushige Yamashita ◽  
Hiroaki Kosaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiac Myocytes ◽  
Myocardial Injury ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
No Donor ◽  
Oxide Synthase ◽  
Gpx Activity

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined. Interleukin-1β induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS,l-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso- N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2(0.1 mM, 1 h). Inhibition of iNOS with Nω-nitro-l-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

scholarly journals Curcumin Decreased Oxidative Stress, Inhibited NF-κB Activation, and Improved Liver Pathology in Ethanol-Induced Liver Injury in Rats

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Suchittra Samuhasaneeto ◽  
Duangporn Thong-Ngam ◽  
Onanong Kulaputana ◽  
Doungsamon Suyasunanont ◽  
Naruemon Klaikeaw
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Early Stage ◽  
Control Group ◽  
Liver Pathology ◽  
Sprague Dawley ◽  
Hepatocyte Apoptosis ◽  
Sod Activity ◽  
Ethanol Group ◽  
Liver Histopathology

To study the mechanism of curcumin-attenuated inflammation and liver pathology in early stage of alcoholic liver disease, female Sprague-Dawley rats were divided into four groups and treated with ethanol or curcumin via an intragastric tube for 4 weeks. A control group treated with distilled water, and an ethanol group was treated with ethanol (7.5 g/kg bw). Treatment groups were fed with ethanol supplemented with curcumin (400 or 1 200 mg/kg bw). The liver histopathology in ethanol group revealed mild-to-moderate steatosis and mild necroinflammation. Hepatic MDA, hepatocyte apoptosis, and NF-κB activation increased significantly in ethanol-treated group when compared with control. Curcumin treatments resulted in improving of liver pathology, decreasing the elevation of hepatic MDA, and inhibition of NF-κB activation. The 400 mg/kg bw of curcumin treatment revealed only a trend of decreased hepatocyte apoptosis. However, the results of SOD activity, PPARγprotein expression showed no difference among the groups. In conclusion, curcumin improved liver histopathology in early stage of ethanol-induced liver injury by reduction of oxidative stress and inhibition of NF-κB activation.

Changes in [Ca2+]i induced by several glucose transport-enhancing stimuli in rat epitrochlearis muscle

2003 ◽  
Vol 94 (5) ◽  
pp. 1813-1820 ◽  
Author(s):  
Shin Terada ◽  
Isao Muraoka ◽  
Izumi Tabata
Keyword(s):  
Glucose Transport ◽  
Quantitative Information ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Concentration Dependent Manner ◽  
Fura 2 ◽  
Sprague Dawley Rats ◽  
Intracellular Ca ◽  
Resting Muscle ◽  
Krebs Henseleit Buffer

The purpose of the present investigation was to establish a method for estimating intracellular Ca2+ concentrations ([Ca2+]i) in isolated rat epitrochlearis muscles. Epitrochlearis muscles excised from 4-wk-old male Sprague-Dawley rats were loaded with a fluorescent Ca2+indicator, fura 2-AM, for 60–90 min at 35°C in oxygenated Krebs-Henseleit buffer. After fura 2 loading and subsequent 20-min incubation, the intensities of 500-nm fluorescence, induced by 340- and 380-nm excitation lights (Ftotal340 and Ftotal380), were measured. The fluorescences specific to fura-2 (Ffura 2340 and Ffura 2380) were calculated by subtracting the non-fura 2-specific component from Ftotal340 and Ftotal380, respectively. The ratio of Ffura 2340 to Ffura 2380 was calculated as R, and the change in the ratio from the baseline value (ΔR) was used as an index of the change in [Ca2+]i. In resting muscle, ΔR was stable for 60 min. Incubation for 20 min with caffeine (3–10 mM) significantly increased ΔR in a concentration-dependent manner. Incubation with hypoxic Krebs-Henseleit buffer for 10–60 min significantly elevated ΔR, depending on the duration of the incubation. Incubation with 50 μM N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide for 20 min significantly elevated ΔR ( P < 0.05). No significant increases in ΔR were observed during incubation for 20 min with 2 mM 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside or with 2 mU/ml insulin. These results demonstrated that, by using the fura 2-AM fluorescence method, the changes in [Ca2+]i can be monitored in the rat epitrochlearis muscle and suggest that the method can be utilized to observe quantitative information regarding [Ca2+]i that may be involved in contraction- and hypoxia-stimulated glucose transport activity in skeletal muscle.

Dipyridamole Potentiates the Endothelium-Dependent and -Independent Vasomotion in Isolated Human Small Arteries

1996 ◽  
Vol 1 (3) ◽  
pp. 203-209 ◽  
Author(s):  
Roberto Pedrinelli
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Adenosine Receptor ◽  
Guanosine Monophosphate ◽  
Muscarinic Agonist ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adenosine Receptor Agonist ◽  
Synthase Inhibitor

Background To investigate the effects of dipyridamole, a drug with phosphodiesterase-, adenosine reuptake-inhibiting, and prostacyclin-stimulating activity on the biological actions of nitric oxide, 30 norepinephrine-precontracted subcutaneous arterioles were prepared from specimens removed during surgery. Methods and Results Specimens were mounted on a myograph and relaxed through either acetylcholine, a muscarinic agonist that stimulates endothelial nitric oxide production, or sodium nitroprusside, an endothelium-independent vasodilator. Studies were performed under control conditions and after dipyridamole which potentiated in a concentration-dependent manner the vasorelaxation induced both by acetylcholine and sodium nitroprusside, indicating an endothelium-independent mechanism of action. The contribution of nitric oxide to the relaxation produced by acetylcholine was confirmed by N-monomethyl-L-arginine, a nitric oxide synthase inhibitor. In contrast, indomethacin, a cyclo-oxygenase inhibitor, was ineffective, indicating that prostacyclin stimulation could not explain the effect of dipyridamole. CGS 21680 C, an A2-selective adenosine receptor agonist insensitive to tissue deaminase, did not influence the relaxations induced by acetylcholine, suggesting that interference with adenosine metabolism was not implicated in the potentiating action of dipyridamole. Conclusion Dipyridamole potentiated the vasorelaxing effect of acetylcholine and sodium nitroprusside in human subcutaneous arterioles; neither prostacyclin stimulation nor A2 adenosine receptor stimulation could explain this effect. The data are consistent with an increase in intracellular cyclic 3’ 5'-guanosine monophosphate levels secondary to the phosphodiesterase-inhibiting properties of the drug.

Activation of endothelin ETB receptors increases glomerular cGMP via an L-arginine-dependent pathway

1992 ◽  
Vol 263 (6) ◽  
pp. F1020-F1025 ◽  
Author(s):  
R. M. Edwards ◽  
M. Pullen ◽  
P. Nambi
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Binding Sites ◽  
Soluble Guanylate Cyclase ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
High Affinity ◽  
Dependent Pathway ◽  
Stimulation Of

The effects of endothelins (ET) on guanosine 3',5'-cyclic monophosphate (cGMP) levels in intact rat glomeruli were examined. ET-3 produced a rapid approximately fivefold increase in cGMP levels with the maximum effect occurring at 1 min. The ET-3-induced increase in cGMP accumulation occurred in the absence and presence of 3-isobutyl-1-methylxanthine. ET-1, ET-2, ET-3, and the structurally related toxin, sarafotoxin S6c, all increased glomerular cGMP levels in a concentration-dependent manner and with similar potencies (EC50 approximately 15-30 nM). The L-arginine analogue, N omega-nitro-L-arginine (L-NNA), reduced basal levels of cGMP and also totally inhibited ET-induced increases in cGMP as did methylene blue, an inhibitor of soluble guanylate cyclase. The effect of L-NNA was attenuated by L-arginine but not by D-arginine. The stimulation of cGMP accumulation by ET-3 was dependent on extracellular Ca2+ and was additive to atriopeptin III but not to acetylcholine. The ETA-selective antagonist, BQ 123, had no effect on ET-3-induced formation of cGMP. Glomerular membranes displayed high-affinity (Kd = 130-150 pM) and high-density (approximately 2.0 pmol/mg) binding sites for 125I-ET-1 and 125I-ET-3. ET-1, ET-3, and sarafotoxin S6c displaced 125I-ET-1 binding to glomerular membranes with similar affinities. BQ 123 had no effect on 125I-ET-1 binding. We conclude that ET increases cGMP levels in glomeruli by stimulating the formation of a nitric oxide-like factor that activates soluble guanylate cyclase. This effect of ET appears to be mediated by activation of ETB receptors and may serve to modulate the contractile effects of ET.

Fire Ant Venom Alkaloid, Isosolenopsin A, a Potent and Selective Inhibitor of Neuronal Nitric Oxide Synthase

2003 ◽  
Vol 22 (2) ◽  
pp. 81-86 ◽  
Author(s):  
G. B. Yi ◽  
D. Mc Clendon ◽  
D. Desaiah ◽  
J. Goddard ◽  
A. Lister ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inhibitory Activity ◽  
Systemic Toxicity ◽  
Fire Ant ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Nos Inhibitors ◽  
Oxide Synthase ◽  
Nos Isoforms

Massive, multiple fire ant, Solenopsis invicta, stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown. To assess a possible pharmacological basis for systemic toxicity, an alkaloid-rich, protein-free methanol extract of the venom from whole ants was assayed for inhibitory activity on the following nitric oxide synthase (NOS) isoforms, rat cerebellar neuronal (n NOS), bovine recombinant endothelial (e NOS), and murine recombinant immunologic (i NOS). Cytosolic NOS activity was determined by measuring the conversion of [3H]arginine to [3H]citrulline in vitro. Rat n NOS activity was inhibited significantly and in a concentration-dependent manner by the alkaloid-rich venom extract. For n NOS, enzyme activity was inhibited by approximately 50% with 0.33 ± 0.06 μgg of this venom extract, and over 95% inhibition of the three isoforms, n NOS, e NOS, and i NOS, was found with doses of 60 μg in 60-μl reaction mixture. These results indicate that the alkaloid components of S. invicta venom can produce potent inhibition of all three major NOS isoforms. Isosolenopsin A ( cis-2-methyl-6-undecylpiperidine), a naturally occurring fire ant piperidine alkaloid, was synthesized and tested for inhibitory activity against the three NOS isoforms. Enzyme activities for n NOS and e NOS were over 95% inhibited with 1000 μM of isosolenopsin A, whereas the activity of i NOS was inhibited by only about 20% at the same concentration. The IC50 for each of three NOS isoforms was approximately 18 ± 3.9 μM for n NOS, 156 ± 10 μM for e NOS, and >1000 μM for i NOS, respectively. Kinetic studies showed isosolenopsin A inhibition to be noncompetitive with L-arginine ( Ki = 19 ± 2 μM). The potency of isosolenopsin A as an inhibitor of n NOS compares favorably with the inhibitory potency of widely used n NOS inhibitors. Inhibition of NOS isoforms by isosolenopsin A and structurally similar compounds may have toxicological significance with respect to adverse reactions to fire ant stings.

scholarly journals Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial V̇o2 during exercise

2012 ◽  
Vol 303 (1) ◽  
pp. R94-R100 ◽  
Author(s):  
Robert Boushel ◽  
Teresa Fuentes ◽  
Ylva Hellsten ◽  
Bengt Saltin
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Ex Vivo ◽  
Knee Extension ◽  
Physiological Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Nitric oxide (NO) and prostaglandins (PG) together play a role in regulating blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome- c oxidase. Indomethacin uncouples and inhibits the electron transport chain in a concentration-dependent manner, and thus, inhibition of NO and PG synthesis may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG synthesis blockade (l-NMMA and indomethacin, respectively) on mitochondrial respiration in human muscle following knee extension exercise (KEE). Specifically, this study examined the physiological effect of NO, and the pharmacological effect of indomethacin, on muscle mitochondrial function. Consistent with their mechanism of action, we hypothesized that inhibition of nitric oxide synthase (NOS) and PG synthesis would have opposite effects on muscle mitochondrial respiration. Mitochondrial respiration was measured ex vivo by high-resolution respirometry in saponin-permeabilized fibers following 6 min KEE in control (CON; n = 8), arterial infusion of NG-monomethyl-l-arginine (l-NMMA; n = 4) and Indo ( n = 4) followed by combined inhibition of NOS and PG synthesis (l-NMMA + Indo, n = 8). ADP-stimulated state 3 respiration (OXPHOS) with substrates for complex I (glutamate, malate) was reduced 50% by Indo. State 3 O2 flux with complex I and II substrates was reduced less with both Indo (20%) and l-NMMA + Indo (15%) compared with CON. The results indicate that indomethacin reduces state 3 mitochondrial respiration primarily at complex I of the respiratory chain, while blockade of NOS by l-NMMA counteracts the inhibition by Indo. This effect on muscle mitochondria, in concert with a reduction of blood flow accounts for in vivo changes in muscle O2 consumption during combined blockade of NOS and PG synthesis.

scholarly journals Extracellular ATP inhibits transport in medullary thick ascending limbs: role of P2X receptors

2009 ◽  
Vol 297 (5) ◽  
pp. F1168-F1173 ◽  
Author(s):  
Guillermo B. Silva ◽  
Jeffrey L. Garvin
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Receptor Antagonist ◽  
P2x Receptors ◽  
Extracellular Atp ◽  
Thick Ascending Limb ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Nitric Oxide Synthase Inhibitor

Absorption of NaCl by the thick ascending limb (TAL) involves active transport and therefore depends on oxidative phosphorylation. Extracellular ATP has pleiotropic effects, including both stimulation and inhibition of transport and inhibition of oxidative phosphorylation. However, it is unclear whether ATP alters TAL transport and how this occurs. We hypothesized that ATP inhibits TAL Na absorption by reducing Na entry. We measured oxygen consumption in TAL suspensions. ATP reduced oxygen consumption in a concentration-dependent manner. The purinergic (P2) receptor antagonist suramin (300 μM) blocked the effect of ATP on TAL oxygen consumption (147 ± 15 vs. 146 ± 16 nmol O2·min−1·mg protein−1). In contrast, the adenosine receptor antagonist theophylline did not block the effect of ATP on oxygen consumption. When Na-K-2Cl cotransport and Na/H exchange were blocked with furosemide (100 μM) plus dimethyl amiloride (100 μM), ATP did not inhibit TAL oxygen consumption (from 78 ± 13 to 98 ± 5 nmol O2·min−1·mg protein−1). The Na ionophore nystatin (200 U/ml) increased TAL oxygen consumption to a similar extent in both ATP- and vehicle-treated samples (368 ± 41 vs. 397 ± 47 nmol O2·min−1·mg protein−1). The nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (3 mM) blocked the ATP effects on TAL oxygen consumption (157 ± 10 vs. 165 ± 15 nmol O2·min−1·mg protein−1). The P2X-selective receptor antagonist NF023 blocked the effect of ATP on oxygen consumption, whereas the P2X-selective agonist β-γ-Me-ATP reduced oxygen consumption in a concentration-dependent manner. We conclude that ATP inhibits Na transport-related oxygen consumption in TALs by reducing Na entry and P2X receptors and nitric oxide mediate this effect.

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