Effects of modulation of nitric oxide on rat diaphragm isotonic contractility during hypoxia

2003 ◽  
Vol 94 (2) ◽  
pp. 612-620 ◽  
Author(s):  
Xiaoping Zhu ◽  
Leo M. A. Heunks ◽  
Herwin A. Machiels ◽  
Leo Ennen ◽  
P. N. Richard Dekhuijzen
Keyword(s):  
Nitric Oxide ◽  
Power Generation ◽  
Muscle Contraction ◽  
Fatigue Properties ◽  
Rat Diaphragm ◽  
Shortening Velocity ◽  
No Donor ◽  
Diaphragm In Vitro ◽  
Spermine Nonoate

Nitric oxide (NO) is essential for optimal myofilament function of the rat diaphragm in vitro during active shortening. Little is known about the role of NO in muscle contraction under hypoxic conditions. Hypoxia might increase the NO synthase (NOS) activity within the rat diaphragm. We hypothesized that NO plays a protective role in isotonic contractile and fatigue properties during hypoxia in vitro. The effects of the NOS inhibitor N G-monomethyl-l-arginine (l-NMMA), the NO scavenger hemoglobin, and the NO donor spermine NONOate on shortening velocity, power generation, and isotonic fatigability during hypoxia were evaluated (Po 2 ∼ 7 kPa). l-NMMA and hemoglobin slowed the shortening velocity, depressed power generation, and increased isotonic fatigability during hypoxia. The effects ofl-NMMA were prevented by coadministration with the NOS substrate l-arginine. Spermine NONOate did not alter isotonic contractile and fatigue properties during hypoxia. These results indicate that endogenous NO is needed for optimal muscle contraction of the rat diaphragm in vitro during hypoxia.

Nitric oxide enhances hydrogen peroxide-mediated endothelial permeability in vitro

1997 ◽  
Vol 273 (5) ◽  
pp. C1581-C1587 ◽  
Author(s):  
Naotsuka Okayama ◽  
Christopher G. Kevil ◽  
Loisann Correia ◽  
David Jourd’Heuil ◽  
Makoto Itoh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Permeability ◽  
Reactive Oxygen ◽  
Iron Chelator ◽  
Reactive Oxygen Metabolites ◽  
No Donor ◽  
Spermine Nonoate ◽  
Oxygen Metabolites

The objective of this study was to evaluate the effects of nitric oxide (NO) on H2O2-mediated endothelial permeability. H2O2(0.1 mM) increased permeability at 90 min to 298% of baseline. Spermine NONOate (SNO), an NO donor, at 0.1 or 1 mM did not alter permeability. However, 0.1 mM H2O2+ 1 mM SNO increased permeability to 764%, twice that of 0.1 mM H2O2alone. These treatments were not directly toxic to endothelial cells. This NO effect was concentration dependent, inasmuch as 0.1 mM SNO did not significantly change H2O2-mediated permeability. The NO-enhanced, H2O2-dependent permeability required the simultaneous presence of NO and H2O2, inasmuch as preincubation with SNO for 30 min followed by 0.1 mM H2O2did not alter permeability. Staining of endothelial junctions showed widening of the intercellular space only in junctions of cells exposed to H2O2(0.1 mM) + SNO (1 mM). Furthermore, NO did not affect H2O2metabolism by endothelial cells but significantly depleted intracellular glutathione. This reduction of cell glutathione produced by NO exposure recovered 15–30 min after removal of the NO donor. NO-enhanced permeability was completely blocked by methionine (1 mM), a scavenger of reactive oxygen species, and by the iron chelator desferrioxamine (0.1 mM). These results suggest that NO may exacerbate the effects of H2O2-dependent increase in endothelial monolayer permeability via the iron-catalyzed formation of reactive oxygen metabolites.

Nitric oxide effects on shortening velocity and power production in the rat diaphragm

1996 ◽  
Vol 80 (3) ◽  
pp. 1065-1069 ◽  
Author(s):  
R. J. Morrison ◽  
C. C. Miller ◽  
M. B. Reid
Keyword(s):  
Nitric Oxide ◽  
Isometric Force ◽  
Maximum Velocity ◽  
Power Production ◽  
Ringer Solution ◽  
Fiber Bundles ◽  
Rat Diaphragm ◽  
Shortening Velocity ◽  
No Donor ◽  
Velocity Of Shortening

The present experiments tested nitric oxide (NO) effects on shortening velocity and power production in maximally activated rat diaphragm. Diaphragm fiber bundles (n = 10/group) were incubated at 37 degrees C in Krebs-Ringer solution containing no added drug (control), the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA; 10 mM), the NO donor sodium nitroprusside (SNP; 1 mM), or a combination (L-NNA + SNP) Loaded shortening velocity was measured via the load-clamp technique over a range of afterloads. Force-velocity data were fitted to the Hill equation to determine maximum velocity of shortening (Vmax). Unloaded shortening velocity was measured in control and L-NNA-treated bundles (n = 12/group) by using the slack test. Maximal isometric force and unloaded shortening velocity were not altered by L-NNA. In contrast, L-NNA decreased maximum velocity of shortening (P < 0.05), loaded shortening velocity (P < 0.0001), and power production (P < 0.0001). All L-NNA effects were prevented by coincubating fiber bundles with L-NNA + SNP. SNP alone had no effect on any variable. These data indicate that endogenous NO is essential for optimal myofilament function during active shortening.

Endogenous nitric oxide inhibits chloride transport in the thick ascending limb

1999 ◽  
Vol 276 (1) ◽  
pp. F159-F163 ◽  
Author(s):  
Craig F. Plato ◽  
Barbara A. Stoos ◽  
Ding Wang ◽  
Jeffrey L. Garvin
Keyword(s):  
Nitric Oxide ◽  
Chloride Transport ◽  
Thick Ascending Limb ◽  
Chloride Flux ◽  
Nacl Transport ◽  
No Donor ◽  
Endogenous Nitric Oxide ◽  
Spermine Nonoate

Nitric oxide (NO) inhibits transport in various nephron segments, and the thick ascending limb of the loop of Henle (TALH) expresses NO synthase (NOS). However, the effects of NO on TALH transport have not been extensively studied. We hypothesized that endogenously produced NO directly decreases NaCl transport by the TALH. We first determined the effect of exogenously added NO on net chloride flux ( J Cl). The NO donor spermine NONOate (SPM; 10 μM) decreased J Cl from 101.2 ± 9.6 to 65.0 ± 7.7 pmol ⋅ mm−1 ⋅ min−1, a reduction of 35.5 ± 6.4%, whereas controls did not decrease over time. To determine whether endogenous NO affects cortical TALH transport, we measured the effect of adding the NOS inhibitor N G-nitro-l-arginine methyl ester (l-NAME), the substratel-arginine (l-Arg), or its enantiomerd-arginine (d-Arg) on J Cl.l-NAME andd-Arg did not alter J Cl; in contrast, addition of 0.5 mM l-Arg decreased J Cl by 40.2 ± 10.4% from control. The inhibition of chloride flux by 0.5 mM l-Arg was abolished by pretreatment with l-NAME, indicating that cortical TALH NOS is active, but production of NO is substrate-limited in our preparation. Furthermore, cortical TALH chloride flux increased following removal of 0.5 mMl-Arg from the bath, indicating that the reductions in chloride flux observed in response tol-Arg are not the result of NO-mediated cytotoxicity. We conclude that 1) exogenous NO decreases cortical TALH J Cl; 2) cortical TALHs produce NO in the presence of l-Arg, which decreases J Cl; and 3) the response of cortical TALHs to l-Arg is reversible in vitro. These data suggest an important role for locally produced NO, which may act via an autocrine mechanism to directly affect TALH sodium chloride transport. Thus TALH NO synthesis and inhibition of chloride transport may contribute to the diuretic and natriuretic effects of NO observed in vivo.

scholarly journals Nitric oxide stimulates glucose transport and metabolism in rat skeletal muscle in vitro

1997 ◽  
Vol 322 (1) ◽  
pp. 223-228 ◽  
Author(s):  
Martin E. YOUNG ◽  
George K. RADDA ◽  
Brendan LEIGHTON
Keyword(s):  
Nitric Oxide ◽  
Glucose Metabolism ◽  
Glucose Transport ◽  
Glucose Oxidation ◽  
Glycogen Synthesis ◽  
No Donor ◽  
Lactate Release ◽  
Ly 83583 ◽  
Spermine Nonoate

1. The effects of the nitric oxide (NO) donor sodium nitroprusside (SNP) on the rates of glucose transport and utilization and its interaction with insulin were investigated in rat soleus muscle in vitro. SNP stimulated the rate of 2-deoxyglucose transport and insulin-mediated (100 Ɓ-units/ml) rates of both net and [14C]lactate release and the rate of glucose oxidation. The effects of SNP were independent of the concentration-dependent effects of insulin on glucose metabolism. 2. SNP stimulated the insulin-stimulated rates of net and [14C]lactate release and glucose oxidation in a concentration-dependent manner. The rate of [14C]lactate release was also stimulated by another NO donor, (Z)-1-(N-[aminopropyl]-N-[4-(3-aminopropylammonio)butyl]-amino)-diazen-1-ium-1,2-diolate (spermine NONOate). 3. SNP at 5, 10 and 15 mM inhibited the insulin-stimulated rate of glycogen synthesis and this rate was further decreased at 20 and 25 mM SNP. SNP did not affect the rate of glycogen synthesis in the absence of insulin. 4. Haemoglobin, which is a NO scavenger, prevented the stimulation of the rates of [14C]lactate release by SNP or spermine NONOate. 5. The cGMP content was increased maximally (by approx. 80-fold) within 15 min by SNP (15 mM). The cGMP content, raised maximally by SNP, was significantly decreased by the guanylate cyclase inhibitor LY-83583 (10 ƁM). The cGMP analogue 8-bromo-cGMP (100 ƁM) significantly increased the rate of net lactate release. 6. LY-83583 significantly inhibited SNP-stimulated rates of 2-deoxyglucose transport, [14C]lactate release and glucose oxidation. Methylene Blue (another guanylate cyclase inhibitor) also inhibited SNP-stimulated rates of [14C]lactate release. 7. The results suggest that in rat skeletal muscle: (a) nitric oxide (from SNP or spermine NONOate) increases the rate of glucose transport and metabolism, an effect independent of insulin; (b) SNP inhibits insulin-mediated rates of glycogen synthesis; (c) SNP stimulates cGMP formation, which mediates, at least partly, the effects on glucose metabolism; (d) nitric oxide-mediated stimulation of glucose utilization might occur in fibre contraction. The implications of the effects of NO on glucose metabolism are discussed.

scholarly journals Action of Insulin on Transport of l-Alanine into Rat Diaphragm in Vitro

1973 ◽  
Vol 248 (18) ◽  
pp. 6450-6455
Author(s):  
Thomas R. Riggs ◽  
K. Janet McKirahan
Keyword(s):  
Rat Diaphragm ◽  
Diaphragm In Vitro

Nitric oxide preconditioning regulates endothelial monolayer integrity via the heat shock protein 90-soluble guanylate cyclase pathway

2007 ◽  
Vol 292 (2) ◽  
pp. H893-H903 ◽  
Author(s):  
Galina N. Antonova ◽  
Connie M. Snead ◽  
Alexander S. Antonov ◽  
Christiana Dimitropoulou ◽  
Richard C. Venema ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Injury ◽  
Soluble Guanylate Cyclase ◽  
Heat Shock Protein 90 ◽  
Protective Effects ◽  
No Donor ◽  
Spermine Nonoate

Large (pathological) amounts of nitric oxide (NO) induce cell injury, whereas low (physiological) NO concentrations often ameliorate cell injury. We tested the hypotheses that pretreatment of endothelial cells with low concentrations of NO (preconditioning) would prevent injury induced by high NO concentrations. Apoptosis, induced in bovine aortic endothelial cells (BAECs) by exposing them to either 4 mM sodium nitroprusside (SNP) or 0.5 mM N-(2-aminoethyl)- N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) for 8 h, was abolished by 24-h pretreatment with either 100 μM SNP, 10 μM spermine NONOate, or 100 μM 8-bromo-cGMP (8-Br-cGMP). Repair of BAECs following wounding, measured as the recovery rate of transendothelial electrical resistance, was delayed by 8-h exposure to 4 mM SNP, and this delay was significantly attenuated by 24-h pretreatment with 100 μM SNP. NO preconditioning produced increased association and expression of soluble guanyl cyclase (sGC) and heat shock protein 90 (HSP90). The protective effect of NO preconditioning, but not the injurious effect of 4 mM SNP, was abolished by either a sGC activity inhibitor 1H-[1,2,4]oxadiazolo-[4,3- a]quinoxalin-1-one (ODQ) or a HSP90 binding inhibitor (radicicol) and was mimicked by 8-Br-cGMP. We conclude that preconditioning with a low dose of NO donor accelerates repair and maintains endothelial integrity via a mechanism that includes the HSP90/sGC pathway. HSP90/sGC may thus play a role in the protective effects of NO-generating drugs from injurious stimuli.

Nitric Oxide-Donating Derivatives of Chrysin Stimulate Angiogenesis and Upregulating VEGF Production

2011 ◽  
Vol 340 ◽  
pp. 363-368 ◽  
Author(s):  
Xiao Qing Zou ◽  
Yong Lan Ding ◽  
Sheng Ming Peng ◽  
Chang Ping Hu ◽  
Han Wu Deng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Therapeutic Option ◽  
Therapeutic Angiogenesis ◽  
Vegf Mrna ◽  
No Donor ◽  
Endothelial Migration ◽  
Nitric Oxide Releasing ◽  
Derivatives Of

Angiogenesis, the development of new capillaries from pre-existing vessels, requires the coordinate activation of endothelial cells, which migrate and proliferate to form functional vessels. Endothelial dysfunction and decreased nitric oxide bioavailability may underscore the impairment of angiogenesis. As such, the delivery of exogenous NO is an attractive therapeutic option that has been used to therapeutic angiogenesis. In this paper, a novel group of hybrid nitric oxide-releasing chrysin derivatives was synthesized. The results indicated that all these chrysin derivatives exhibited promotion of endothelial migration and tubulogenesis in vitro as well as stimulation angiogenesis in vivo.Furthermore, all compounds released NO upon incubation with phosphate buffer at pH 7.4 and enhanced VEGF secretion and VEGF mRNA expression of endothelial cells. These hybrid ester NO donor prodrugs offer a potential drug design concept for the development of therapeutic or preventive agents for angiogenesis deficiency due to ischemic diseases.

Abstract P607: Nitric Oxide (NO) Regulates Paracellular Permselectivity in Isolated, Perfused Rat Thick Ascending Limbs through Claudin-19

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Casandra M Monzon ◽  
Jeffrey Garvin
Keyword(s):  
Nitric Oxide ◽  
Control Period ◽  
Sprague Dawley ◽  
Permeability Ratio ◽  
Ionic Selectivity ◽  
No Donor ◽  
Sprague Dawley Rats ◽  
Spermine Nonoate ◽  
Dilution Potential ◽  
Cl Permeability

About 50% of the Na reabsorbed in thick ascending limbs (TALs) traverses the paracellular pathway. The ionic selectivity of this route is regulated by claudins in the tight junctions. TALs express claudin-19 which has been reported to regulate TAL Na permeability. We showed that nitric oxide (NO) decreases Na/Cl permeability ratio (PNa/PCl) in TALs by increasing the absolute permeabilities of both ions though PCl increased more. However, whether NO affects paracellular permeability via claudin-19 is unknown. We hypothesize that NO regulates the paracellular permselectivity in TALs through this claudin. To test this we perfused TALs from Sprague Dawley rats and measured dilution potentials (a measure of permselectivity) with and without exogenously-added or endogenously-produced NO in the presence or absence of an antibody against an extracellular domain of claudin-19 or Tamm-Horsfall protein (control). Dilution potentials were generated by reducing bath NaCl from 141 to 32 mM. For the NO donor spermine NONOate (SPM): during the control period, the dilution potential was -9.3 ± 1.8 mV. After SPM (200 μM), it was -6.7 ± 1.6 mV (n = 6; p < 0.003). In the presence of the claudin-19 antibody, SPM had no significant effect on dilution potentials (claudin-19 antibody alone: -12.7 ± 2.1 mV vs claudin-19 antibody + SPM: -12.9 ± 2.4 mV; n = 6). The claudin-19 antibody alone had no effect on dilution potentials. In the presence of the Tamm-Horsfall protein, the effect of SPM was still present (Tamm-Horsfall protein antibody alone: -9.7 ± 1.0 mV; Tamm-Horsfall protein antibody + SPM: -6.3 ± 1.1 mV, p<0.006, n = 6). For experiments with endogenously-produced NO, L-arginine the substrate for NO synthase was added. During the control period, the dilution potential was -11.0 ± 1.1 mV. After L-arginine (500 μM) treatment, they were -9.0 ± 1.2 mV (n = 9; p < 0.05). In the presence of the claudin-19 antibody, L-arginine had no significant effect on dilution potentials (claudin-19 antibody alone: -10.1 ± 0.9 mV vs claudin-19 antibody + L-arginine: -10.1 ± 1.0 mV; n = 9). In the presence of the Tamm-Horsfall protein, the effect of L-arginine was still present. We conclude that the actions of NO on the paracellular permselectivity in thick ascending limbs are at least in part mediated by claudin-19.

scholarly journals Dephosphorylation of Nucleoside Triphosphates by Rat Diaphragm in vitro.

1957 ◽  
Vol 11 ◽  
pp. 1078-1079 ◽  
Author(s):  
Aa. Rye Alertsen ◽  
O. Walaas ◽  
E. Walaas ◽  
K. E. Almin ◽  
Arne Magnéli ◽  
...  
Keyword(s):  
Rat Diaphragm ◽  
Nucleoside Triphosphates ◽  
Diaphragm In Vitro
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