Vascular responses to sodium nitroprusside in the human fetal-placental circulation

1995 ◽  
Vol 7 (6) ◽  
pp. 1557 ◽  
Author(s):  
MA Read ◽  
WB Giles ◽  
IM Leitch ◽  
AL Boura ◽  
WA Walters
Keyword(s):  
Sodium Nitroprusside ◽  
Vascular Function ◽  
No Production ◽  
Low Oxygen ◽  
Experimental Conditions ◽  
Arterial Perfusion ◽  
Basal Tone ◽  
Intra Uterine Growth Retardation ◽  
Synthase Inhibitor

This study examined the activity of sodium nitroprusside (SNP) in the human fetal-placental circulation in vitro in pathological and experimental conditions in which vascular function may be impaired. SNP (13-3400 nM) caused a concentration-dependent reduction in fetal arterial perfusion pressure (FAP) in Krebs' perfused placental cotyledons, at basal tone and following pre-constriction with prostaglandin F2 alpha (PGF2 alpha). SNP-induced reduction in FAP in the PGF2 alpha pre-constricted fetal-placental circulation was enhanced approximately six-fold (5.85) in those placentae pre-treated with the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (100 microM). Reductions in FAP in the preconstricted fetal-placental vasculature caused by SNP were not altered by prior infusion of ouabain (100 nM) into the fetal circulation or during low oxygen perfusion (O2 tension < 50 mmHg). No differences were observed in the responses obtained to SNP in placentae obtained from women with normotensive pregnancies or those associated with (i) pregnancy-induced hypertension, (ii) intra-uterine growth retardation, or (iii) an elevated umbilical-artery Doppler-ultrasound systolic/diastolic ratio, in either preconstricted placentae or those at basal tone. These findings are consistent with an up-regulation of guanylate cyclase/cGMP-mediated vasodilatation in the fetal-placental vasculature following complete blockade of endogenous NO production.

scholarly journals Effects of aging and exercise training on spinotrapezius muscle microvascular Po2 dynamics and vasomotor control

2011 ◽  
Vol 110 (3) ◽  
pp. 695-704 ◽  
Author(s):  
Danielle J. McCullough ◽  
Robert T. Davis ◽  
James M. Dominguez ◽  
John N. Stabley ◽  
Christian S. Bruells ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Sodium Nitroprusside ◽  
Vascular Function ◽  
Treadmill Running ◽  
Aged Rats ◽  
Phosphorescence Quenching

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O2 delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O2 delivery to O2 uptake, evidenced through improved microvascular Po2 (PmO2), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ∼6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify PmO2 in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline PmO2 (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting PmO2 and the time-delay before PmO2 fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the PmO2 in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.

Caspase Activation Is Required for Nitric Oxide–Mediated, CD95(APO-1/Fas)–Dependent and Independent Apoptosis in Human Neoplastic Lymphoid Cells

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4311-4320 ◽  
Author(s):  
Katerina Chlichlia ◽  
Marcus E. Peter ◽  
Marian Rocha ◽  
Carsten Scaffidi ◽  
Mariana Bucur ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Present Report ◽  
Lymphoid Cells ◽  
Jurkat Cells ◽  
Target Cells ◽  
No Production ◽  
No Donor ◽  
Synthase Inhibitor ◽  
Inhibitor Of Protein Synthesis

Abstract Nitric oxide (NO), an important effector molecule involved in immune regulation and host defense, was shown to induce apoptosis in lymphoma cells. In the present report the NO donor glycerol trinitrate was found to induce apoptosis in Jurkat cells that are sensitive to CD95-mediated kill. In contrast, a CD95-resistant Jurkat subclone showed substantial protection from apoptosis after exposure to NO. NO induced mRNA expression of CD95 (APO-1/Fas) and TRAIL/APO-2 ligands. Moreover, NO triggered apoptosis in freshly isolated human leukemic lymphocytes which were also sensitive to anti-CD95 treatment. The ability of NO to induce apoptosis was completely blocked by a broad-spectrum ICE (interleukin-1β converting enzyme)-protease/caspase inhibitor and correlated with FLICE/caspase-8 activation. This activation was abrogated in some neoplastic lymphoid cells but not in others by the inhibitor of protein synthesis cycloheximide. Our results were confirmed using an in vitro experimental model of coculture of human lymphoid target cells with activated bovine endothelial cells generating NO as effectors. Furthermore, the inhibition of endogenous NO production with the inducible NO synthase inhibitor NG-monomethyl-L-arginine caused a complete abrogation of the apoptotic effect. Our data provide evidence that NO-induced apoptosis in human neoplastic lymphoid cells strictly requires activation of caspases, in particular FLICE, the most CD95 receptor-proximal caspase. Depending on the cell line tested this activation required or was independent of the CD95 receptor/ligand system.

Sources and implications of basal nitric oxide in spontaneous contractions of guinea pig taenia caeci

2003 ◽  
Vol 285 (4) ◽  
pp. G747-G753 ◽  
Author(s):  
Catalina Caballero-Alomar ◽  
Carmen Santos ◽  
Diego Lopez ◽  
M. Teresa Mitjavila ◽  
Pere Puig-Parellada
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Inhibitory Effect ◽  
No Production ◽  
Paramagnetic Resonance ◽  
Synthase Inhibitor ◽  
Spontaneous Contractions ◽  
Electron Paramagnetic

We examined in vitro the source and role of basal nitric oxide (NO) in proximal segments of guinea pig taenia caeci in nonadrenergic, noncholinergic (NANC) conditions. Using electron paramagnetic resonance (EPR), we measured the effect of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 10–4 M), the neuronal blocker tetrodotoxin (TTX, 10–6 M), or both on spontaneous contractions and on the production of basal NO. Both l-NAME and TTX, when tested alone, increased the amplitude and frequency of contractions. NO production was abolished by l-NAME and was inhibited by 38% by TTX. When tested together, l-NAME in the presence of TTX or TTX in the presence of l-NAME had no further effect on the amplitude or frequency of spontaneous contractions, and the NO production was inhibited. These findings suggest that basal NO consists of TTX-sensitive and TTX-resistant components. The TTX-sensitive NO has an inhibitory effect on spontaneous contractions; the role of TTX-resistant NO is unknown.

scholarly journals Differential regulation of endothelium behavior by progesterone and medroxyprogesterone acetate

2013 ◽  
Vol 220 (3) ◽  
pp. 179-193 ◽  
Author(s):  
Pablo H Cutini ◽  
Adrián E Campelo ◽  
Virginia L Massheimer
Keyword(s):  
Medroxyprogesterone Acetate ◽  
Vascular Function ◽  
Platelet Adhesion ◽  
Hormone Replacement ◽  
Differential Regulation ◽  
No Production ◽  
Stimulatory Action ◽  
Pi3k Inhibitor Ly294002 ◽  
Inflammatory Conditions

Medroxyprogesterone acetate (MPA) is a synthetic progestin commonly used in hormone replacement therapy (HRT). The aim of this research was to study and compare the effect of progesterone (Pg) and MPA on the regulation of cellular events associated with vascular homeostasis and disease. Platelet adhesion to endothelial cells (ECs), nitric oxide (NO) production, and cell migration were studied using murine ECs in vitro exposed to the progestins. After 7 min of treatment, MPA significantly inhibited NO synthesis with respect to control values; meanwhile, Pg markedly increased vasoactive production. In senile ECs, the stimulatory action of Pg decreases; meanwhile, MPA maintained its ability to inhibit NO synthesis. The presence of RU486 antagonized the action of each steroid. When ECs were preincubated with PD98059 (MAPK inhibitor) or chelerythrine (protein kinase C (PKC) inhibitor) before Pg or MPA treatment, the former totally suppressed the steroid action, but the PKC antagonist did not affect NO production. In the presence of a PI3K inhibitor (LY294002), a partial reduction in Pg effect and a reversal of MPA action were detected. Using indomethacin, the contribution of the cyclooxygenase (COX) pathway was also detected. On platelet adhesion assays, Pg inhibited and MPA stimulated platelet adhesion to ECs. Under inflammatory conditions, Pg prevented platelet adhesion induced by lipopolysaccharide (LPS); meanwhile, MPA potentiated the stimulatory action of LPS. Finally, although both steroids enhanced migration of ECs, MPA exhibited a greater effect. In conclusion, the data presented in this research provide evidence of a differential regulation of vascular function by Pg and MPA.

Antivasoconstrictor and Antiaggregatory Activities of Picotamide Unrelated to Thromboxane A2 Antagonism

1997 ◽  
Vol 78 (05) ◽  
pp. 1385-1391 ◽  
Author(s):  
Roberta Vezza ◽  
Domenico Spina ◽  
Ronald J Tallarida ◽  
Malevika Nathan ◽  
Clive P Page ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Shape Change ◽  
Thromboxane A2 ◽  
Inhibitory Effects ◽  
Experimental Conditions ◽  
Vasoactive Substances ◽  
Vasoconstrictor Effect ◽  
Synthase Inhibitor

SummaryPicotamide is a dual thromboxane (Tx) A2 receptor antagonist/Tx synthase inhibitor although some observations suggest an anti-vasoconstrictor effect independent of TxA2 inhibition/antagonism. The aim of our study was to assess whether picotamide antagonises vascular contractions induced by different vasoactive substances in vitro. Picotamide inhibited competitively the contraction of rabbit aortic rings induced by the TxA2 mimetic U46619 (pA2 = 3.59) but also the contractions induced by phenylephrine (pA2 = 3.93) and serotonin (5-HT) (pA2 = 5.81) although in a not competitive way. Picotamide did not inhibit potassium-induced contractions, thus excluding aspecific effects on vascular smooth muscle. Picotamide inhibited 5-HT-induced platelet aggregation in vitro with an IC50 (212 μM) similar to that found when other aggregating stimuli are used, but it did not affect shape change (IC50> 1 mM) suggesting that the effects of picotamide can not be ascribed to 5-HT2-receptor antagonism; in the same experimental conditions neither a Tx-receptor antagonist (BM13.177) nor a dual Tx-receptor antagonist/synthase inhibitor (ridogrel) affected 5-HT-induced platelet responses.Our studies demonstrate that picotamide exerts antivasoconstrictor and platelet inhibitory effects unrelated to TxA2 antagonism. This activity may contribute to the anti-thrombotic/anti-ischaemic effects of the drug in vivo.

Caspase Activation Is Required for Nitric Oxide–Mediated, CD95(APO-1/Fas)–Dependent and Independent Apoptosis in Human Neoplastic Lymphoid Cells

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4311-4320 ◽  
Author(s):  
Katerina Chlichlia ◽  
Marcus E. Peter ◽  
Marian Rocha ◽  
Carsten Scaffidi ◽  
Mariana Bucur ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Present Report ◽  
Lymphoid Cells ◽  
Jurkat Cells ◽  
Target Cells ◽  
No Production ◽  
No Donor ◽  
Synthase Inhibitor ◽  
Inhibitor Of Protein Synthesis

Nitric oxide (NO), an important effector molecule involved in immune regulation and host defense, was shown to induce apoptosis in lymphoma cells. In the present report the NO donor glycerol trinitrate was found to induce apoptosis in Jurkat cells that are sensitive to CD95-mediated kill. In contrast, a CD95-resistant Jurkat subclone showed substantial protection from apoptosis after exposure to NO. NO induced mRNA expression of CD95 (APO-1/Fas) and TRAIL/APO-2 ligands. Moreover, NO triggered apoptosis in freshly isolated human leukemic lymphocytes which were also sensitive to anti-CD95 treatment. The ability of NO to induce apoptosis was completely blocked by a broad-spectrum ICE (interleukin-1β converting enzyme)-protease/caspase inhibitor and correlated with FLICE/caspase-8 activation. This activation was abrogated in some neoplastic lymphoid cells but not in others by the inhibitor of protein synthesis cycloheximide. Our results were confirmed using an in vitro experimental model of coculture of human lymphoid target cells with activated bovine endothelial cells generating NO as effectors. Furthermore, the inhibition of endogenous NO production with the inducible NO synthase inhibitor NG-monomethyl-L-arginine caused a complete abrogation of the apoptotic effect. Our data provide evidence that NO-induced apoptosis in human neoplastic lymphoid cells strictly requires activation of caspases, in particular FLICE, the most CD95 receptor-proximal caspase. Depending on the cell line tested this activation required or was independent of the CD95 receptor/ligand system.

scholarly journals Practical Considerations of Dissolved Oxygen Levels for Platelet Function under Hypoxia

2021 ◽  
Vol 22 (24) ◽  
pp. 13223
Author(s):  
Branden Kusanto ◽  
Andrew Gordon ◽  
Leigh Naylor-Adamson ◽  
Lloyd Atkinson ◽  
Charlie Coupland ◽  
...  
Keyword(s):  
Dissolved Oxygen ◽  
Platelet Function ◽  
Platelet Rich Plasma ◽  
Atmospheric Conditions ◽  
Low Oxygen ◽  
Experimental Conditions ◽  
Sample Handling ◽  
Oxygen Levels ◽  
Platelet Spreading

Investigating human platelet function in low-oxygen environments is important in multiple settings, including hypobaric hypoxia (e.g., high altitude), sea level hypoxia-related disease, and thrombus stability. These studies often involve drawing blood from which platelets are isolated and analysed at atmospheric conditions or re-exposed to low oxygen levels in hypoxia chambers before testing. However, it remains unknown how the in vitro handling of the samples itself changes their dissolved oxygen concentration, which might affect platelet function and experimental results. Here, we prepared healthy donor platelet-rich plasma and washed platelet (WP) suspensions and exposed them to 2% oxygen. We found that the use of hypoxia pre-equilibrated tubes, higher platelet concentrations (>2 × 108/mL versus 2 × 107/mL), smaller volumes (600 µL versus 3 mL), and presence of plasma reduced the time for samples to reach 2% oxygen. Notably, oxygen levels decreased below 2% in most suspensions, but also in WP maintained at atmospheric 21% oxygen. Additionally, platelet spreading on fibrinogen was decreased when using hypoxic fibrinogen-coated culture plates regardless of the oxygen percentage (2% or 21%) in which platelet incubation took place. Thus, sample handling and experimental conditions should be carefully monitored in platelet-hypoxia studies as they might compromise results interpretation and comparison across studies.

scholarly journals The role of asymmetric dimethylarginine in the development of arterial hypertension.

2018 ◽  
Vol 95 (11) ◽  
pp. 965-970
Author(s):  
V. I. Podzolkov ◽  
T. A. Safronova ◽  
Dinara U. Natkina
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Asymmetric Dimethylarginine ◽  
Biological Marker ◽  
No Production ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor

The results of numerous studies of recent decades confirm the crucial role of vascular endothelium in regulating vascular homeostasis. A plethora of recent studies have shed light on the clinical significance of endothelial dysfunction in essential hypertension. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor. At present, it is considered as a generally recognized marker of endothelial dysfunction by most researchers. In vitro experiments showed that ADMA inhibits endothelium-dependent arterial relaxation, increases the level of indicators characterizing the degree of oxidative stress in endothelial cells, enhances the synthesis of the superoxide anion radical by endothelial cells. The molecular mechanisms described above, activated with an increase in the concentration of ADMA, cause various disturbances in the function of the cardiovascular system, which gave grounds to consider the level of ADMA as a criterion and risk factor for the development of cardiovascular diseases. Thus, ADMA plays a key role in the development and progression of CVD associated with a spectrum of diseases and pathological conditions characterized by a disturbance in NO production. Despite clinical and experimental confirmation of the relationship between the increase in ADMA in plasma and the development of cardiovascular events, the unambiguous etiopathogenetic role of ADMA in CVD requires further research. In order to accurately answer the question of whether ADMA is an etiological factor or a biological marker of CVD, additional analysis is needed to study the biochemical, genetic and pharmacological aspects of ADMA metabolism, the results of which are presented in this article.

scholarly journals Stimulation of Macrophage Cells Against Cutaneous Leishmaniasis Using Silver Nanoparticles

2019 ◽  
Vol 16 (2) ◽  
pp. 0299
Author(s):  
Al-Saeedi Et al.
Keyword(s):  
Silver Nanoparticles ◽  
Cutaneous Leishmaniasis ◽  
No Production ◽  
Ag Nps ◽  
Experimental Conditions ◽  
Spectrum Activity ◽  
Viability Percentage ◽  
Ldh Release ◽  
Species Production

Cutaneous leishmaniasis is a disease caused by Leishmania tropica parasite. Current treatments for this parasite are undesirable because of their toxicity, resistance, and high cost. Macrophages are key players against pathogens. Nitric oxide (NO), a molecule produce by immune cells, controls intracellular killing of pathogens during infection. Silver nanoparticles (Ag NPs) demonstrated broad-spectrum activity against various types of infectious diseases. It has the ability to stimulate oxygen species production.  This study aims to analyze the macrophages activation through NO production and estimate the cytotoxicity based on the lactate dehydrogenase (LDH) release upon exposure to L. tropica and Ag NPs. Serially concentrations of Ag NPs were used under two conditions during and following macrophages exposure to L. tropica. MTT assay was used to determine the cytotoxicity of Ag NPs on L. tropica amastigotes during infection of macrophages in vitro. The results showed that by increasing the Ag NPs concentrations, the viability percentage of L. tropica amastigotes decreased and reached to 21.7 ± 0.64 % during infection compared with the control. The 50% inhibitory concentration of Ag NPs on amastigotes was 2.048µg/ml during infection. Moreover, post-phagocytosis study involved the assessment of NO and LDH release by macrophages upon exposure to L. tropica. It have shown that untreated macrophages released low levels of NO while in the presence of Ag NPs, macrophages were activated to produce higher levels of NO under all experimental conditions. On the other hand, macrophages were capable of controlling cytotoxicity and decreasing LDH levels during phagocytosis of L. tropica amastiogotes. Taking together, these findings suggest that Ag NPs can enhance macrophages NO production which provides a method for the identification of Ag NPs ligands with microbicidal and anti-cytotoxic properties against L. tropica pathogens.

Hypoxia promotes nucleus pulposus phenotype in 3D scaffolds in vitro and in vivo

2014 ◽  
Vol 21 (2) ◽  
pp. 303-309 ◽  
Author(s):  
Ganjun Feng ◽  
Li Li ◽  
Ying Hong ◽  
Hao Liu ◽  
Yueming Song ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Collagen Type ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Low Oxygen ◽  
Nucleus Pulposus Cells ◽  
Experimental Conditions ◽  
3D Scaffolds

Object The role of oxygen in disc metabolism remains a matter of debate. Whether the effect of hypoxic priming on the nucleus pulposus phenotype can be maintained in vivo is not clear. The goal of the present study was to test the hypothesis that priming in a low oxygen tension in vitro could promote a nucleus pulposus phenotype in vivo. Methods Bovine nucleus pulposus cells were seeded in 3D scaffolds and subjected to varying oxygen tensions (2% and 20%) for 3 weeks. The constructs were then implanted subcutaneously for 8 weeks. Changes in the extracellular matrix were evaluated using quantitative real-time reverse transcriptase polymerase chain reaction, glycosaminoglycan (GAG) assay, DNA assay, collagen quantification, and histological and immunohistological analyses. Results Hypoxia resulted in greater production of sulfated glycosaminoglycan and higher levels of gene expression for collagen Type II, aggrecan, and SOX-9. Furthermore, after hypoxic priming, the subcutaneously implanted constructs maintained the nucleus pulposus phenotype, which was indicated by a significantly higher amount of glycosaminoglycan and collagen Type II. Conclusions Hypoxia enhanced the nucleus pulposus phenotype under experimental conditions both in vitro and in vivo. When used in combination with appropriate scaffold material, nucleus pulposus cells could be regenerated for tissue-engineering applications.

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