scholarly journals Inhaled nitric oxide decreases pulmonary endothelial nitric oxide synthase expression and activity in normal newborn rat lungs

2016 ◽  
Vol 2 (1) ◽  
pp. 00060-2015 ◽  
Author(s):  
Thông Hua-Huy ◽  
Sy Duong-Quy ◽  
Hoa Pham ◽  
Julien Pansiot ◽  
Jean-Christophe Mercier ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Expression ◽  
Inhaled Nitric Oxide ◽  
Control Group ◽  
Enos Gene ◽  
Newborn Rat ◽  
Enos Expression ◽  
Rat Pups ◽  
Rat Lungs ◽  
Expression And Activity

Inhaled nitric oxide (iNO) is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS) activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats.Rat pups, post-natal day (P) 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group) or 20 ppm (iNO-20 ppm group), or in room air (control group). Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity.At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7.Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.

Oxygen upregulates nitric oxide synthase gene expression in ovine fetal pulmonary artery endothelial cells

1996 ◽  
Vol 270 (4) ◽  
pp. L643-L649 ◽  
Author(s):  
A. J. North ◽  
K. S. Lau ◽  
T. S. Brannon ◽  
L. C. Wu ◽  
L. B. Wells ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Protein Expression ◽  
Oxygen Tension ◽  
Enos Gene ◽  
Enos Expression ◽  
Ovine Fetal ◽  
Enos Protein Expression ◽  
Enos Protein

Nitric oxide (NO) is critically involved in oxygen-mediated pulmonary vasodilatation in the fetus and newborn. We determined the effects of prolonged alterations in oxygenation on endothelial NO synthase (eNOS) gene expression in early passage ovine fetal intrapulmonary artery endothelial cells (PAEC). PAEC were exposed to PO2 = 50 or 150 mmHg for 48 h, and eNOS protein expression was evaluated by immunoblot analysis. eNOS protein expression was 2.7-fold greater at higher oxygen tension; eNOS upregulation was also evident after 24 h. Inducible NOS protein was not detectable by immunoblot at either level of oxygenation. In the lung, the effect of oxygen on eNOS expression may be specific to the endothelium, as eNOS expression in bronchiolar epithelial cells of Clara cell lineage was not altered by varying oxygen tension. The oxygen-related increase in eNOS protein in the fetal PAEC was associated with 2.5-fold greater NOS enzymatic activity. In parallel, there was a 2.8-fold rise in eNOS mRNA abundance. Thus eNOS gene expression in ovine fetal PAEC is upregulated by oxygen, and this is mediated at the level of gene transcription or mRNA stability. This process may play an important role in oxygen modulation of pulmonary vasomotor tone in the fetus and newborn.

scholarly journals Modulation of Pulmonary Cytochrome P4501A1 Expression by Hyperoxia and Inhaled Nitric Oxide in the Newborn Rat: Implications for Lung Injury

2006 ◽  
Vol 59 (3) ◽  
pp. 401-406 ◽  
Author(s):  
Xanthi I Couroucli ◽  
Yan-Hong Wei ◽  
Weiwu Jiang ◽  
Kathirvel Muthiah ◽  
Lee W Evey ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Injury ◽  
Inhaled Nitric Oxide ◽  
Newborn Rat ◽  
Cytochrome P4501a1

Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension

1997 ◽  
Vol 272 (5) ◽  
pp. L1005-L1012 ◽  
Author(s):  
P. W. Shaul ◽  
I. S. Yuhanna ◽  
Z. German ◽  
Z. Chen ◽  
R. H. Steinhorn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pulmonary Hypertension ◽  
Protein Expression ◽  
Enzymatic Activity ◽  
Ductus Arteriosus ◽  
Muscle Growth ◽  
No Synthase ◽  
Enos Gene ◽  
Enos Expression ◽  
Enos Protein

Nitric oxide (NO), produced by endothelial (e) NO synthase (NOS), is critically involved in the cardiopulmonary transition from fetal to neonatal life. We have previously shown that NO-dependent relaxation is attenuated in intrapulmonary arteries from fetal lambs with pulmonary hypertension (PHT) created by prenatal ligation of the ductus arteriosus. In the present study, we determined whether this is due to altered pulmonary eNOS expression. eNOS and neuronal NOS (nNOS) protein expression were assessed in lungs from near-term control lambs and PHT lambs that underwent ductal ligation 10 days earlier. eNOS protein expression was decreased 49% in PHT lung. In contrast, nNOS protein abundance was unchanged. NOS enzymatic activity was also diminished in PHT vs. control lung (60 +/- 3 vs. 110 +/- 7 fmol.mg protein-1.min-1, respectively). Paralleling the declines in eNOS protein and NOS enzymatic activity, eNOS mRNA abundance was decreased 64% in PHT lung. Thus pulmonary eNOS gene expression is attenuated in the lamb model of fetal PHT. Because NO modulates both vasodilation and vascular smooth muscle growth, diminished eNOS expression may contribute to both the abnormal vasoreactivity and the excessive muscularization of the pulmonary circulation in fetal PHT.

scholarly journals The Effect of Inhaled Nitric Oxide and Oxygen on the Hydroxylation of Salicylate in Rat Lungs

2003 ◽  
Vol 54 (3) ◽  
pp. 337-343 ◽  
Author(s):  
Leif D Nelin ◽  
James F Morrisey ◽  
Richard M Effros ◽  
Christopher A Dawson ◽  
Ralph M Schapira
Keyword(s):  
Nitric Oxide ◽  
Inhaled Nitric Oxide ◽  
Rat Lungs

scholarly journals A Feasibility Trial to Evaluate the Composite Efficacy of Inhaled Nitric Oxide in the Treatment of Covid 19 Pneumonia : Impact on Viral Load and Clinical Outcomes

2021 ◽  
Author(s):  
Merlin Moni ◽  
Thushara Madathil ◽  
Dipu Sathyapalan ◽  
Veena Menon ◽  
Georg Gutjahr ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Viral Load ◽  
Clinical Outcomes ◽  
Tertiary Care ◽  
Inhaled Nitric Oxide ◽  
Feasibility Trial ◽  
Ordinal Scale ◽  
Control Group ◽  
South Indian ◽  
Significant Difference

Background: Hypoxic patients with Covid 19 pneumonia are at high risk of adverse outcomes. Inhaled Nitric Oxide (iNO) inhibits viral entry and replication of SARS-CoV2 and in vivo proof of its antiviral actions is unavailable to date. This feasibility study was conducted to test the antiviral effects of iNO and to describe clinical outcomes. Methods: The phase II open label, randomised controlled feasibility trial(ISRCTN 16806663) conducted at a South Indian tertiary care referral centre, recruited COVID-19 pneumonia patients with hypoxic respiratory failure and allocated them into iNO cases and control groups(1:1). iNO was administered as pulses for 30 minutes for three consecutive days at 12-hour intervals in cases, in addition to standard of care received by the control group. The primary outcome was decline in viral load, as defined by a surrogate change in the RT-PCR cycle threshold. The co-primary clinical outcome was time to improvement of >2 points on the WHO Ordinal Scale(WOS). Results: Among the 29 patients enrolled, 14 iNO cases and 11 controls completed the study protocol. Longitudinal analysis revealed a significant difference in the decline (p <0.002, N= 23) in viral load among the iNO cases compared to controls. The proportion of patients achieving 2-point improvement in the WOS within 14 days of randomisation was significantly higher in the iNO cases (n=11, 79%), as compared to the controls (n=4, 36%) (p=0.05). Conclusions: Our study demonstrated significant improvement in virological and clinical outcomes among patients with adjunct iNO therapy and no adverse effects were reported.

Aspirin Protected the Nitric Oxide/Cyclic Gmp Generating System in Human Peritoneum

2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 48-53 ◽  
Author(s):  
Maria M. Arriero ◽  
Angel Celdran ◽  
Petra Jimenez ◽  
Antonio García–Mendez ◽  
Juan C. De La Pinta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Expression ◽  
Soluble Guanylate Cyclase ◽  
Dependent Manner ◽  
Enos Expression ◽  
Tissue Samples ◽  
Peritoneal Tissue ◽  
Capillary Endothelial Cells ◽  
Anti Inflammatory ◽  
Enos Protein

♦ Objective Changes in the expression of endothelial nitric oxide synthase (eNOS) in the peritoneum could be involved in the peritoneal dysfunction associated with peritoneal inflammation. The aim of the present study was to analyze the effect of Escherichia coli lipopolysaccharide (LPS) on eNOS expression in samples of human peritoneum. The effect of aspirin, a drug with anti-inflammatory properties, was also determined. ♦ Results The eNOS protein expressed in human peritoneal tissue was reduced by LPS (10 μg/mL) in a time-dependent manner. The eNOS was expressed mainly in capillary endothelial cells and mesothelial cells. Anti-inflammatory doses of aspirin (1 – 10 mmol/L) restored eNOS expression in LPS-stimulated human peritoneal tissue samples. The main intracellular receptor of NO, soluble guanylate cyclase (sGC), was also downregulated by LPS. This effect was prevented by aspirin (5 mmol/L). ♦ Conclusion Protein expression of the eNOS–sGC system in the peritoneal tissue was downregulated by LPS. High doses of aspirin protected both eNOS protein expression and sGC in human peritoneum. These findings suggest a new mechanism of action of aspirin that could be involved in the prevention of peritoneal dysfunction during inflammation.

Prevalence of common polymorphisms of AT-rich interaction domain 1A and endothelial nitric oxide synthase in patients with endometriosis compared to control group

2018 ◽  
Vol 10 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Zohreh Tavana ◽  
Azadeh Khalili ◽  
Golnaz Namazi ◽  
Ahmad Ebrahimi ◽  
Sara Davoodi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Control Group ◽  
Enos Gene ◽  
Interaction Domain ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Rich Interaction ◽  
Glu298asp Polymorphism

Introduction: Endometriosis is a common gynecologic disorder defined as ectopic presence of endometrial tissue in extrauterine sites. Endometriosis is associated with infertility and risk of malignancy. Identification of genetic factors responsible for development and malignant transformation of endometriosis can improve therapeutic approaches. In this study, we investigated the association of AT-rich interaction domain 1A ( ARID1A) and endothelial nitric oxide synthase ( eNOS) polymorphisms with endometriosis and staging of the disease. Methods: A total of 100 women with laparoscopy-confirmed diagnosis of endometriosis were included and compared with 100 women without endometriosis as the control group. Genotypes of patients regarding Gln920Ter polymorphism of ARID1A gene and Glu298Asp polymorphism of eNOS gene were determined by polymerase chain reaction techniques on blood samples from the study population. The prevalence of each genotype in endometriosis patients was compared with healthy controls using the chi-square test. Results: Significantly higher prevalence of non-CC genotype for ARID1A Gln920Ter polymorphism and non-GG genotype for G894T polymorphism of the eNOS gene was detected in the endometriosis group. There was no significant relationship between these polymorphisms and staging of endometriosis. Discussion: Significant variation of prevalence of Gln920Ter polymorphism of the ARID1A gene and Glu298Asp polymorphism of the eNOS gene among the two groups can indicate a causative effect of these genetic alterations on the development of endometriosis.

Inhaled Nitric Oxide Inhibits Platelet Aggregation after Pulmonary Embolism in Pigs

1997 ◽  
Vol 86 (2) ◽  
pp. 387-393 ◽  
Author(s):  
Andre Gries ◽  
Bernd W. Bottiger ◽  
Joachim Dorsam ◽  
Harry Bauer ◽  
Jorg Weimann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Embolism ◽  
Platelet Aggregation ◽  
Thrombus Formation ◽  
Carbon Dioxide Concentration ◽  
Right Ventricular Dysfunction ◽  
Inhaled Nitric Oxide ◽  
Control Group ◽  
Maximum Decrease ◽  
Inhaled No

Background Inhaled nitric oxide (NO) is reported to prolong bleeding time in animals and humans and to inhibit platelet aggregation in persons with acute respiratory distress syndrome. In pulmonary embolism (PE), inhibition of platelet aggregation appears useful because further thrombus formation may lead to right ventricular dysfunction that results in circulatory failure. In the present study, the effect of inhaled NO on platelet aggregation after acute massive PE was investigated. Methods After acute massive PE was induced in 25 anesthetized pigs by injecting microspheres, 5, 20, 40, and 80 parts per million inhaled NO were administered stepwise for 10 min each in 11 animals (NO group). In the control group (n = 14). NO was not administered. Adenosine diphosphate-induced initial and maximal platelet aggregation were measured before PE (10), immediately after induction of PE (PE), at the end of each 10-min NO inhalation interval (t10-t40), and 15 min after cessation of NO inhalation (t55) in the NO group, and at corresponding times in the control group, respectively. Results Two animals in the control group and one in the NO group died within 10 min after PE induction and were excluded from analysis. Peaking at t40 and t55, respectively, initial (-13 +/- 6%; P &lt; 0.05) and maximal (+44 +/- 17%; P &lt; 0.05) platelet aggregation increased significantly after PE in the control group. In contrast, NO administration after PE led to a significant decrease in initial (maximum decrease, -9 +/- 3% at t40; P &lt; 0.05) and maximal (maximum decrease, -15 +/- 7% at t30; P &lt; 0.05) platelet aggregation. In the NO group, platelet aggregation had returned to baseline levels again at t55. In addition, NO administration significantly decreased mean pulmonary artery pressure and significantly increased end-tidal carbon dioxide concentration and mean systemic blood pressure. Conclusions Inhaled NO has a systemic and rapidly reversible inhibitory effect on platelet aggregation after acute massive PE in pigs. This may be beneficial in treating acute massive PE.

scholarly journals NO Level and Endothelial NO Synthase Gene Polymorphism (Glu298Asp) in the Patients with Coronary Artery Disease from the Turkish Population

2004 ◽  
Vol 36 (10) ◽  
pp. 661-666 ◽  
Author(s):  
Lale Afrasyap ◽  
Guler Ozturk
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Gene Polymorphism ◽  
Turkish Population ◽  
Control Group ◽  
Enos Gene ◽  
Nitric Oxide Level ◽  
Significant Difference ◽  
Artery Disease

Abstract Nitric oxide is synthesized from L-arginine by endothelial nitric oxide synthase encoded by eNOS gene. This study was performed to investigate the relationship between the serum nitric oxide level and eNOS gene polymorphism in the Turkish population with angiographically diagnosed coronary artery disease (63.47 ± 9.10 years old, n=250) and control subjects without any history and/or risk factors of coronary artery disease (60.71 ± 9.14 years old, n=150). Griess assay and PCR-RFLP analysis were used to measure the serum nitric oxide metabolites and genotypes, respectively. It was found that Glu/Glu, Glu/Asp and Asp/ Asp genotype frequencies of the eNOS were 49.3%, 41.3% and 9.3% respectively in the control group, and 45.6%, 41.2% and 13.2% in the patient group. Serum nitric oxide levels were (32.56 ± 17.26) μM in controls and (29.84 ± 11.88) μM in patients. Neither the frequencies of the Glu298Asp genotypes nor the serum nitric oxide levels showed a significant difference between the groups. There was also no correlation between serum nitric oxide levels and the frequencies of the eNOS genotypes. Result showed that the coronary artery disease of the Turkish population seemed to develop without any alterations in eNOS Glu298Asp genotype frequency and the serum nitric oxide level.

Sign in / Sign up

Export Citation Format

Share Document