Inhaled NO as a therapeutic agent

Bloch, Kenneth D.; Ichinose, Fumito; Roberts, Jesse D.; Zapol, Warren M.

doi:10.1016/j.cardiores.2007.04.014

Cited by 142 publications

(106 citation statements)

References 93 publications

(106 reference statements)

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“…Inhaled NO gas was approved as therapeutic agent by the US Food and Drug Administration (FDA) in 1999 and the European Medicine Evaluation Agency and European Commission in 2001. It has since been used as a pulmonary vasodilator in treating pulmonary hypertension, including in patients with chronic obstructive pulmonary disease (COPD) [116,117]. However, the effect of inhaled NO on bacterial infections during these treatments was not investigated.…”

Section: Use Of No Gasmentioning

confidence: 99%

Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

Barraud¹,

Kelso²,

Rice

et al. 2014

CPD

221

196

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Studies of the biofilm life cycle can identify novel targets and strategies for improving biofilm control measures. Of particular interest are dispersal events, where a subpopulation of cells is released from the biofilm community to search out and colonize new surfaces. Recently, the simple gas and ubiquitous biological signaling molecule nitric oxide (NO) was identified as a key mediator of biofilm dispersal conserved across microbial species. Here, we review the role and mechanisms of NO mediating dispersal in bacterial biofilms, and its potential for novel therapeutics. In contrast to previous attempts using high dose NO aimed at killing pathogens, the use of low, non-toxic NO signals (picomolar to nanomolar range) to disperse biofilms represents an innovative and highly favourable approach to improve infectious disease treatments. Further, several NO-based technologies have been developed that offer a versatile range of solutions to control biofilms, including: (i) NO-generating compounds with short or long half-lives and safe or inert residues, (ii) novel compounds for the targeted delivery of NO to infectious biofilms during systemic treatments, and (iii) novel NO-releasing materials and surface coatings for the prevention and dispersal of biofilms. Overall the use of low levels of NO exploiting its signaling properties to induce dispersal represents an unprecedented and promising strategy for the control of biofilms in clinical and industrial contexts. AbstractStudies of the biofilm life cycle can identify novel targets and strategies for improving biofilm control measures. Of particular interest are dispersal events, where a subpopulation of cells is released from the biofilm community to search out and colonize new surfaces. Recently, the simple gas and ubiquitous biological signaling molecule nitric oxide (NO) was identified as a key mediator of biofilm dispersal conserved across microbial species. Here, we review the role and mechanisms of NO mediating dispersal in bacterial biofilms, and its potential for novel therapeutics. In contrast to previous attempts using high dose NO aimed at killing pathogens, the use of low, non-toxic NO signals (picomolar to nanomolar range) to disperse biofilms represents an innovative and highly favourable approach to improve infectious disease treatments. Further, several NO-based technologies have been developed that offer a versatile range of solutions to control biofilms, including: (i) NO-generating compounds with short or long half-lives and safe or inert residues, (ii) novel compounds for the targeted delivery of NO to infectious biofilms during systemic treatments, and (iii) novel NO-releasing materials and surface coatings for the prevention and dispersal of biofilms. Overall the use of low levels of NO exploiting its signaling properties to induce dispersal represents an unprecedented and promising strategy for the control of biofilms in clinical and industrial contexts. 3 Increased antimicrobial tolerance in biofilms is the basis for chronic infecti...

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Section: Use Of No Gasmentioning

confidence: 99%

Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

Barraud¹,

Kelso²,

Rice

et al. 2014

CPD

221

196

View full text Add to dashboard Cite

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“…Minneci and coworkers (16) demonstrated that inhaled NO reversed the pulmonary hypertension produced by hemoglobin infusion in dogs. Many thousands of patients with acute pulmonary hypertension have been successfully treated with inhaled NO (13,33). In children with pulmonary endothelial dysfunction proved by a lack of response to acetylcholine infusion, and pulmonary hypertension following extracorporeal bypass, Wessel and coworkers (34) showed that PAP was normalized by breathing NO.…”

Section: Original Articlementioning

confidence: 99%

“…Circulating hemoglobin, both free in plasma and contained in shed microparticles, avidly scavenges NO via the dioxygenation reaction, depleting vascular NO levels and resulting in vasoconstriction (11). Because pulmonary vasoconstriction was produced in animal models by stored RBC transfusion and prevented by breathing NO (12), we previously tested whether breathing low levels of NO could selectively dilate the pulmonary circulation without producing systemic vasodilation or hypotension (13).…”

mentioning

confidence: 99%

Autologous Transfusion of Stored Red Blood Cells Increases Pulmonary Artery Pressure

Berra

Pinciroli

Stowell

et al. 2014

Am J Respir Crit Care Med

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Rationale: Transfusion of erythrocytes stored for prolonged periods is associated with increased mortality. Erythrocytes undergo hemolysis during storage and after transfusion. Plasma hemoglobin scavenges endogenous nitric oxide leading to systemic and pulmonary vasoconstriction.Objectives: We hypothesized that transfusion of autologous blood stored for 40 days would increase the pulmonary artery pressure in volunteers with endothelial dysfunction (impaired endothelial production of nitric oxide). We also tested whether breathing nitric oxide before and during transfusion could prevent the increase of pulmonary artery pressure.Methods: Fourteen obese adults with endothelial dysfunction were enrolled in a randomized crossover study of transfusing autologous, leukoreduced blood stored for either 3 or 40 days. Volunteers were transfused with 3-day blood, 40-day blood, and 40-day blood while breathing 80 ppm nitric oxide.Measurements and Main Results: The age of volunteers was 41 6 4 years (mean 6 SEM), and their body mass index was 33.4 6 1.3 kg/ m 2 . Plasma hemoglobin concentrations increased after transfusion with 40-day and 40-day plus nitric oxide blood but not after transfusing 3-day blood. Mean pulmonary artery pressure, estimated by transthoracic echocardiography, increased after transfusing 40-day blood (18 6 2 to 23 6 2 mm Hg; P , 0.05) but did not change after transfusing 3-day blood (17 6 2 to 18 6 2 mm Hg; P = 0.5). Breathing nitric oxide decreased pulmonary artery pressure in volunteers transfused with 40-day blood (17 6 2 to 12 6 1 mm Hg; P , 0.05).Conclusions: Transfusion of autologous leukoreduced blood stored for 40 days was associated with increased plasma hemoglobin levels and increased pulmonary artery pressure. Breathing nitric oxide prevents the increase of pulmonary artery pressure produced by transfusing stored blood. Clinical trial registered with www.clinicaltrials.gov (NCT 01529502).

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“…23). On the one hand, idiopathic PAH in humans has been represented as an NO-deficiency disease state with the growing use of sildenafil, NO inhalation, and nebulized nitrites as therapeutic approaches in this disease (4,10,11,13,23,29,62,68). On the other hand, varying data have been reported on the relationships between eNOS expression levels and NO activity (23 and citations therein).…”

Section: Discussionmentioning

confidence: 99%

Golgi, trafficking, and mitosis dysfunctions in pulmonary arterial endothelial cells exposed to monocrotaline pyrrole and NO scavenging

Lee

Reich

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lee J, Reich R, Xu F, Sehgal PB. Golgi, trafficking, and mitosis dysfunctions in pulmonary arterial endothelial cells exposed to monocrotaline pyrrole and NO scavenging. Am J Physiol Lung Cell Mol Physiol 297: L715-L728, 2009. First published July 31, 2009 doi:10.1152/ajplung.00086.2009.-Although the administration of monocrotaline (MCT) into experimental animals is in widespread use today in investigations of pulmonary arterial hypertension (PAH), the underlying cellular and subcellular mechanisms that culminate in vascular remodeling are incompletely understood. Bovine pulmonary arterial endothelial cells (PAECs) in culture exposed to monocrotaline pyrrole (MCTP) develop "megalocytosis" 18 -24 h later characterized by enlarged hyperploid cells with enlarged Golgi, mislocalization of endothelial nitric oxide synthase away from the plasma membrane, decreased cell-surface/caveolar nitric oxide (NO), and hypo-S-nitrosylation of caveolin-1, clathrin heavy chain, and N-ethylmaleimidesensitive factor. We investigated whether MCTP did in fact affect functional intracellular trafficking. The NO scavenger (4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) and the NO donor diethylamine NONOate were used for comparison. Both MCTP and c-PTIO produced distinctive four-to fivefold enlarged PAECs within 24 -48 h with markedly enlarged/dispersed Golgi, as visualized by immunostaining for the Golgi tethers/matrix proteins giantin, GM130, and p115. Live-cell uptake of the Golgi marker C5 ceramide revealed a compact juxtanuclear Golgi in untreated PAECs, brightly labeled enlarged circumnuclear Golgi after MCTP, but minimally labeled Golgi elements after c-PTIO. These Golgi changes were reduced by NONOate. After an initial inhibition during the first day, both MCTP and c-PTIO markedly enhanced anterograde secretion of soluble cargo (exogenous vector-expressed recombinant horseradish peroxidase) over the next 4 days. Live-cell internalization assays using fluorescently tagged ligands showed that both MCTP and c-PTIO inhibited the retrograde uptake of acetylated low-density lipoprotein, transferrin, and cholera toxin B. Moreover, MCTP, and to a variable extent c-PTIO, reduced the cell-surface density of all receptors assayed (LDLR, TfnR, BMPR, Tie-2, and PECAM-1/ CD31). In an important distinction, c-PTIO enhanced mitosis in PAECs but MCTP inhibited mitosis, even that due to c-PTIO, despite markedly exaggerated Golgi dispersal. Taken together, these data define a broad-spectrum Golgi and subcellular trafficking dysfunction syndrome in endothelial cells exposed to MCTP or NO scavenging. vascular remodeling; megalocytosis; anterograde and retrograde trafficking; ␤-actin INGESTION OR ADMINISTRATION of pyrrolizidene alkaloids leads to vascular occlusive disease including pulmonary arterial hypertension (PAH) in cattle, horses, pigs, dogs, and even primates (reviewed in Refs. 20, 48 and citations therein). Over the last four decades the experimental administration of the pyrrolizidine alkaloid monocrotaline into r...

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Inhaled NO as a therapeutic agent

Cited by 142 publications

References 93 publications

Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

Autologous Transfusion of Stored Red Blood Cells Increases Pulmonary Artery Pressure

Golgi, trafficking, and mitosis dysfunctions in pulmonary arterial endothelial cells exposed to monocrotaline pyrrole and NO scavenging

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