A Novel Approach to Partition Central and Peripheral Airway Nitric Oxide

CHEST Journal ◽  
2014 ◽  
Vol 145 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Paolo Paredi ◽  
Sergei A. Kharitonov ◽  
Sally Meah ◽  
Peter J. Barnes ◽  
Omar S. Usmani
Keyword(s):  
Nitric Oxide ◽  
Novel Approach ◽  
Peripheral Airway

scholarly journals Collagen IV contributes to nitric oxide-induced angiogenesis of lung endothelial cells

2011 ◽  
Vol 300 (5) ◽  
pp. C979-C988 ◽  
Author(s):  
Huafang Wang ◽  
Yunchao Su
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Wound Repair ◽  
Tube Formation ◽  
Collagen Iv ◽  
Endothelial Monolayer ◽  
No Donor ◽  
Alveolar Capillary Dysplasia ◽  
Novel Approach ◽  
Lung Endothelial Cells

Nitric oxide (NO) mediates endothelial angiogenesis via inducing the expression of integrin αvβ3. During angiogenesis, endothelial cells adhere to and migrate into the extracellular matrix through integrins. Collagen IV binds to integrin αvβ3, leading to integrin activation, which affects a number of signaling processes in endothelial cells. In the present study, we evaluated the role of collagen IV in NO-induced angiogenesis. We found that NO donor 2,2′-(hydroxynitrosohydrazino)bis-ethanamine (NOC-18) causes increases in collagen IV mRNA and protein in lung endothelial cells and collagen IV release into the medium. Addition of collagen IV into the coating of endothelial culture increases endothelial monolayer wound repair, proliferation, and tube formation. Inhibition of collagen IV synthesis using gene silencing attenuates NOC-18-induced increases in monolayer wound repair, cell proliferation, and tube formation as well as in the phosphorylation of focal adhesion kinase (FAK). Integrin blocking antibody LM609 prevents NOC-18-induced increase in endothelial monolayer wound repair. Inhibition of protein kinase G (PKG) using the specific PKG inhibitor KT5823 or PKG small interfering RNA prevents NOC-18-induced increases in collagen IV protein and mRNA and endothelial angiogenesis. Together, these results indicate that NO promotes collagen IV synthesis via a PKG signaling pathway and that the increase in collagen IV synthesis contributes to NO-induced angiogenesis of lung endothelial cells through integrin-FAK signaling. Manipulation of collagen IV could be a novel approach for the prevention and treatment of diseases such as alveolar capillary dysplasia, severe pulmonary arterial hypertension, and tumor invasion.

Central and Peripheral Airway Sites of Nitric Oxide Gas Exchange in COPD

CHEST Journal ◽  
2010 ◽  
Vol 137 (3) ◽  
pp. 575-584 ◽  
Author(s):  
Arthur F. Gelb ◽  
Colleen Flynn Taylor ◽  
Anita Krishnan ◽  
Christine Fraser ◽  
Chris M. Shinar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Gas Exchange ◽  
Peripheral Airway

scholarly journals Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction

Gut ◽  
2017 ◽  
Vol 67 (2) ◽  
pp. 271-283 ◽  
Author(s):  
Emilie Catry ◽  
Laure B Bindels ◽  
Anne Tailleux ◽  
Sophie Lestavel ◽  
Audrey M Neyrinck ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Gut Microbiota ◽  
Vascular Function ◽  
Carotid Arteries ◽  
Rrna Gene ◽  
Gut Peptides ◽  
Novel Approach

ObjectiveTo investigate the beneficial role of prebiotics on endothelial dysfunction, an early key marker of cardiovascular diseases, in an original mouse model linking steatosis and endothelial dysfunction.DesignWe examined the contribution of the gut microbiota to vascular dysfunction observed in apolipoprotein E knockout (Apoe−/−) mice fed an n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks with or without inulin-type fructans (ITFs) supplementation for the last 15 days. Mesenteric and carotid arteries were isolated to evaluate endothelium-dependent relaxation ex vivo. Caecal microbiota composition (Illumina Sequencing of the 16S rRNA gene) and key pathways/mediators involved in the control of vascular function, including bile acid (BA) profiling, gut and liver key gene expression, nitric oxide and gut hormones production were also assessed.ResultsITF supplementation totally reverses endothelial dysfunction in mesenteric and carotid arteries of n-3 PUFA-depleted Apoe−/− mice via activation of the nitric oxide (NO) synthase/NO pathway. Gut microbiota changes induced by prebiotic treatment consist in increased NO-producing bacteria, replenishment of abundance in Akkermansia and decreased abundance in bacterial taxa involved in secondary BA synthesis. Changes in gut and liver gene expression also occur upon ITFs suggesting increased glucagon-like peptide 1 production and BA turnover as drivers of endothelium function preservation.ConclusionsWe demonstrate for the first time that ITF improve endothelial dysfunction, implicating a short-term adaptation of both gut microbiota and key gut peptides. If confirmed in humans, prebiotics could be proposed as a novel approach in the prevention of metabolic disorders-related cardiovascular diseases.

scholarly journals Single passive leg movement assessment of vascular function: contribution of nitric oxide

2017 ◽  
Vol 123 (6) ◽  
pp. 1468-1476 ◽  
Author(s):  
Ryan M. Broxterman ◽  
Joel D. Trinity ◽  
Jayson R. Gifford ◽  
Oh Sung Kwon ◽  
Andrew C. Kithas ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Clinical Utility ◽  
Area Under The Curve ◽  
Vasodilatory Response ◽  
Novel Approach ◽  
Movement Assessment ◽  
No Bioavailability ◽  
Leg Movement

The assessment of passive leg movement (PLM)-induced leg blood flow (LBF) and vascular conductance (LVC) is a novel approach to assess vascular function that has recently been simplified to only a single PLM (sPLM), thereby increasing the clinical utility of this technique. As the physiological mechanisms mediating the robust increase in LBF and LVC with sPLM are unknown, we tested the hypothesis that nitric oxide (NO) is a major contributor to the sPLM-induced LBF and LVC response. In nine healthy men, sPLM was performed with and without NO synthase inhibition by intra-arterial infusion of NG-monomethyl-l-arginine (l-NMMA). Doppler ultrasound and femoral arterial pressure were used to determine LBF and LVC, which were characterized by the peak change (ΔLBFpeak and ΔLVCpeak) and area under the curve (LBFAUC and LVCAUC). l-NMMA significantly attenuated ΔLBFpeak [492 ± 153 (l-NMMA) vs. 719 ± 238 (control) ml/min], LBFAUC [57 ± 34 (l NMMA) vs. 147 ± 63 (control) ml], ΔLVCpeak [4.7 ± 1.1 (l-NMMA) vs. 8.0 ± 3.0 (control) ml·min−1·mmHg−1], and LVCAUC [0.5 ± 0.3 (l-NMMA) vs. 1.6 ± 0.9 (control) ml/mmHg]. The magnitude of the NO contribution to LBF and LVC was significantly correlated with the magnitude of the control responses ( r = 0.94 for ΔLBFpeak, r = 0.85 for LBFAUC, r = 0.94 for ΔLVCpeak, and r = 0.95 for LVCAUC). These data establish that the sPLM-induced hyperemic and vasodilatory response is predominantly (~65%) NO-mediated. As such, sPLM appears to be a promising, simple, in vivo assessment of NO-mediated vascular function and NO bioavailability. NEW & NOTEWORTHY Passive leg movement (PLM), a novel assessment of vascular function, has been simplified to a single PLM (sPLM), thereby increasing the clinical utility of this technique. However, the role of nitric oxide (NO) in mediating the robust sPLM hemodynamic responses is unknown. This study revealed that sPLM induces a hyperemic and vasodilatory response that is predominantly NO-mediated and, as such, appears to be a promising simple, in vivo, clinical assessment of NO-mediated vascular function and, therefore, NO bioavailability.

COPD patients with peripheral airway obstruction reversibility identified by exhaled nitric oxide

2019 ◽  
Vol 13 (3) ◽  
pp. 036002 ◽  
Author(s):  
Silvia Pérez-Bogerd ◽  
Alain Michils ◽  
Andrei Malinovschi ◽  
Alain Van Muylem
Keyword(s):  
Nitric Oxide ◽  
Airway Obstruction ◽  
Exhaled Nitric Oxide ◽  
Copd Patients ◽  
Peripheral Airway

scholarly journals Passive leg movement and nitric oxide-mediated vascular function: the impact of age

2015 ◽  
Vol 308 (6) ◽  
pp. H672-H679 ◽  
Author(s):  
Joel D. Trinity ◽  
H. Jonathan Groot ◽  
Gwenael Layec ◽  
Matthew J. Rossman ◽  
Stephen J. Ives ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Area Under The Curve ◽  
The Elderly ◽  
Novel Approach ◽  
Leg Movement ◽  
The Impact ◽  
Male Subjects ◽  
Peak Increase

In young healthy men, passive leg movement (PLM) elicits a robust nitric oxide (NO)-dependent increase in leg blood flow (LBF), thus providing a novel approach to assess NO-mediated vascular function. While the magnitude of the LBF response to PLM is markedly reduced with age, the role of NO in this attenuated response in the elderly is unknown. Therefore, this study sought to determine the contribution of NO in the PLM-induced LBF with age. Fourteen male subjects (7 young, 24 ± 1 yr; and 7 old, 75 ± 3 yr) underwent PLM with and without NO synthase (NOS) inhibition achieved by intra-arterial infusion of NG-monomethyl-l-arginine (l-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central hemodynamics were measured by finger photoplethysmography. NOS inhibition blunted the PLM-induced peak increase in LBF in the young (control: 668 ± 106; l-NMMA: 431 ± 95 Δml/min; P = 0.03) but had no effect in the old (control: 266 ± 98; l-NMMA: 251 ± 92 Δml/min; P = 0.59). Likewise, the magnitude of the reduction in the overall (i.e., area under the curve) PLM-induced LBF response to NOS inhibition was less in the old (LBF: −31 ± 18 ml) than the young (LBF: −129 ± 21 ml; P < 0.01). These findings suggest that the age-associated reduction in PLM-induced LBF in the elderly is primarily due to a reduced contribution to vasodilation from NO and therefore support the use of PLM as a novel approach to assess NO-mediated vascular function across the lifespan.

scholarly journals Intravesical Nitric Oxide Delivery for Prevention of Catheter-Associated Urinary Tract Infections

2005 ◽  
Vol 49 (6) ◽  
pp. 2352-2355 ◽  
Author(s):  
Stefan Carlsson ◽  
Eddie Weitzberg ◽  
Peter Wiklund ◽  
Jon O. Lundberg
Keyword(s):  
Nitric Oxide ◽  
Ascorbic Acid ◽  
Urinary Tract ◽  
Bacterial Growth ◽  
Laboratory Model ◽  
Strain Atcc ◽  
No Donor ◽  
Novel Approach ◽  
Nitric Oxide Delivery ◽  
Tract Infections

ABSTRACT The use of indwelling urinary catheters is a major risk factor for urinary tract infection; and despite the availability of numerous preventive regimens, this condition is still extremely common. In earlier studies we have demonstrated the inhibitory effects of nitrite and ascorbic acid on bacterial growth in urine. When combined, these compounds generate antibacterial reactive nitrogen species, including the gas nitric oxide. We have now tested in a laboratory model of the urinary bladder whether filling of the catheter retention balloon with nitrite and ascorbic acid would generate measurable amounts of NO outside the membrane and whether this would affect bacterial growth in the surrounding urine. Two strains of Escherichia coli, one strain isolated from a patient (U1106024) and one reference strain (ATCC 25922), were tested. Nitric oxide gas was generated in the silicone balloon and readily diffused into the urine. When control catheters with ascorbic acid but without nitrite were used, bacterial counts increased from 9.0 × 105 to 2.0 ×108 CFU/ml (strain U1106024) and from 2.5 × 106 to 2.7 × 108 CFU/ml (strain ATCC 25922) after 24 h. In contrast, in test catheters with ascorbic acid and nitrite, both strains tested were effectively killed. The NO donor {DETA NONOate, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate} also showed antibacterial activity in the same model, thereby supporting a central role of NO in achieving the observed effects. Future clinical trials will reveal whether this novel approach for the intravesical delivery of an antibacterial gas could be used to prevent catheter-associated infections.

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