The key role of nitric oxide in hypoxia: hypoxic vasodilation and energy supply-demand matching

Significance: a mismatch between energy supply and demand induces tissue hypoxia with the potential to cause cell death and organ failure. Whenever arterial oxygen concentration is reduced, increases in blood flow - 'hypoxic vasodilation' - occur in an attempt to restore oxygen supply. Nitric oxide is a major signalling and effector molecule mediating the body's response to hypoxia, given its unique characteristics of vasodilation (improving blood flow and oxygen supply) and modulation of energetic metabolism (reducing oxygen consumption and promoting utilization of alternative pathways). Recent advances: this review covers the role of oxygen in metabolism and responses to hypoxia, the hemodynamic and metabolic effects of nitric oxide, and mechanisms underlying the involvement of nitric oxide in hypoxic vasodilation. Recent insights into nitric oxide metabolism will be discussed, including the role for dietary intake of nitrate, endogenous nitrite reductases, and release of nitric oxide from storage pools. The processes through which nitric oxide levels are elevated during hypoxia are presented, namely (i) increased synthesis from nitric oxide synthases, increased reduction of nitrite to nitric oxide by heme- or pterin-based enzymes and increased release from nitric oxide stores, and (ii) reduced deactivation by mitochondrial cytochrome c oxidase. Critical issues: several reviews covered modulation of energetic metabolism by nitric oxide, while here we highlight the crucial role NO plays in achieving cardiocirculatory homeostasis during acute hypoxia through both vasodilation and metabolic suppression Future directions: we identify a key position for nitric oxide in the body's adaptation to an acute energy supply-demand mismatc

Titanium dioxide nanotubes for production and delivery of nitric oxide and methods for production thereof

The present disclosure describes compositions operable for releasing nitric oxide under photochemical conditions. The compositions include a titanium dioxide nanomaterial and a nitric oxide-releasing compound deposited on the titanium dioxide nanomaterial that is operable to release nitric oxide under photochemical conditions. Titanium dioxide nanomaterials include, for example, titanium dioxide nanotubes. To facilitate the photochemical release of nitric oxide, some embodiments of the compositions further include a semiconductor that is deposited on the titanium dioxide nanotubes. Both the semiconductor and the nitric oxide-releasing compound may be deposited on the interior surface, exterior surface, or both of the titanium dioxide nanotubes. A polymer may wrap the titanium dioxide nanotubes to protect the nitric oxide-releasing compounds from moisture. Also disclosed herein are methods for producing such compositions and medical devices obtained therefrom.Board of Regents, University of Texas Syste

Reduction of nitric oxide emissions from a combustor

A turbojet combustor and method for controlling nitric oxide emissions by employing successive combustion zones is described. After combustion of an initial portion of the fuel in a primary combustion zone, the combustion products of the primary zone are combined with the remaining portion of fuel and additional plenum air and burned in a secondary combustion zone under conditions that result in low nitric oxide emissions. Low nitric oxide emissions are achieved by a novel turbojet combustor arrangement which provides flame stability by allowing stable combustion to be accompanied by low nitric oxide emissions resulting from controlled fuel-lean combustion (ignited by the emission products from the primary zone) in a secondary combustion zone at a lower combustion temperature resulting in low emission of nitric oxide

Analytical study of mechanisms for nitric oxide formation during combustion of methane in a jet-stirred combustor

The role of chemical kinetics in the formation of nitric oxide during the combustion of methane was examined analytically by means of a detailed chemical mechanism for the oxidation of methane, for the reaction between hydrocarbon fragments, and for the formation of nitric oxide. By comparing predicted nitric oxide levels with values reported in the literature from jet-stirred combuster experiments, it was determined that the nitric oxide levels observed in fuel-rich flames cannot be described by a mechanism in which the rate of nitric oxide formation is controlled solely by the kinetics of oxygen atom formation. A proposed mechanism for the formation of nitric oxide in methane-rich flames reproduces the observed levels. The oxidation of hydrogen cyanide appears to be an important factor in nitric oxide formation

Remarkably strong chemisorption of nitric oxide on insulating oxide films promoted by hybrid structure

The remarkably strong chemical adsorption behaviors of nitric oxide on magnesia (001) film deposited on metal substrate have been investigated by employing periodic density functional calculations with Van der Waals corrections. The molybdenum supported magnesia (001) show significantly enhanced adsorption properties and the nitric oxide is chemisorbed strongly and preferably trapped in flat adsorption configuration on metal supported oxide film, due to the substantially large adsorption energies and transformation barriers. The analysis of Bader charges, projected density of states, differential charge densities, electron localization function, highest occupied orbital and particular orbital with largest Mg-NO-Mg bonding coefficients, are applied to reveal the electronic adsorption properties and characteristics of bonding between nitric oxide and surface as well as the bonding within the hybrid structure. The strong chemical binding of nitric oxide on magnesia deposited on molybdenum slab offers new opportunities for toxic gas detection and treatment. We anticipate that hybrid structure promoted remarkable chemical adsorption of nitric oxide on magnesia in this study will provide versatile strategy for enhancing chemical reactivity and properties of insulating oxide

Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort.

Nitrates, such as cardiac therapeutics and food additives, are common headache triggers, with nitric oxide playing an important role. Facultative anaerobic bacteria in the oral cavity may contribute migraine-triggering levels of nitric oxide through the salivary nitrate-nitrite-nitric oxide pathway. Using high-throughput sequencing technologies, we detected observable and significantly higher abundances of nitrate, nitrite, and nitric oxide reductase genes in migraineurs versus nonmigraineurs in samples collected from the oral cavity and a slight but significant difference in fecal samples. IMPORTANCE Recent work has demonstrated a potentially symbiotic relationship between oral commensal bacteria and humans through the salivary nitrate-nitrite-nitric oxide pathway (C. Duncan et al., Nat Med 1:546-551, 1995, http://dx.doi.org/10.1038/nm0695-546). Oral nitrate-reducing bacteria contribute physiologically relevant levels of nitrite and nitric oxide to the human host that may have positive downstream effects on cardiovascular health (V. Kapil et al., Free Radic Biol Med 55:93-100, 2013, http://dx.doi.org/10.1016/j.freeradbiomed.2012.11.013). In the work presented here, we used 16S rRNA Illumina sequencing to determine whether a connection exists between oral nitrate-reducing bacteria, nitrates for cardiovascular disease, and migraines, which are a common side effect of nitrate medications (U. Thadani and T. Rodgers, Expert Opin Drug Saf 5:667-674, 2006, http://dx.doi.org/10.1517/14740338.5.5.667)

Compositions and medical devices for controlled release of nitric oxide and methods of production thereof

The present disclosure describes compositions providing for controlled release of nitric oxide (NO) and methods for production of these compositions. In some embodiments, the compositions may include a biodegradable polymer and a nitric oxide-releasing material at least partially encapsulated by the biodegradable polymer. Nitric oxide-releasing materials may include, for example, diazeniumdiolates and nitric oxide contained within a zeolite, metal-organic framework or other porous material. In general, the compositions are spun into a porous fiber, which may be further annealed by heating in order to densify the fiber. Annealing may prolong the NO release profile. Medical devices containing the compositions described herein are also contemplated by the present disclosure. Medical devices include, for example, textiles, bandages and articles of clothing.Board of Regents, University of Texas Syste

The Role of Nitric Oxide in Skeletal Simulated Microgravity Response

Prolonged exposure to the space environment leads to bone loss. Using a ground-based model for microgravity (hind-limb unloading), it has been shown in rodents that proliferation and differentiation activity of osteoprogenitors are decreased with exposure to simulated microgravity (Kostenuik et al., 1997). Osteoblast mineralization activity has been shown to increase with nitric oxide supplementation (Afzal et al., 2004; Koyama et al., 2000). I hypothesized that the degenerative effects of microgravity exposure result from chronic changes in nitric oxide regulation in osteoprogenitors, and that supplementation with exogenous nitric oxide following exposure would ameliorate these changes. In 20 C57Bl/6 mice, hind-limb unloading for up to 16 days resulted in degeneration of cancellous tissue in hind-limb bones and a decrease in inducible nitric oxide synthase (iNOS) gene expression in both bone tissue and bone marrow cells. Ex vivo analyses of osteoprogenitor cells, however, showed no changes in differentiation potential or cell count, and supplementation with sodium nitroprusside (SNP) was not able to increase mineralization activity in hind-limb unloaded mice. It is concluded that exogenous nitric oxide supplementation is ineffective as a countermeasure to the effects of simulated microgravity exposure on bone cells

Coupling Between the Thermosphere and the Stratosphere: the Role of Nitric Oxide

In order to understand the lower ionosphere and its probable control by dynamical processes, the behavior of nitric oxide below 100 km was investigated. A two dimensional model with coupled chemical and dynamical processes was constructed. Calculations based on the model reveal that the chemical conditions at the stratopause are related to the state of the thermosphere. This coupling mechanism can be partly explained by the downward transport of nitric oxide during the winter season, and consequently depends on the dynamical conditions in the mesosphere and in the lower thermosphere (mean circulation and waves). In summer, the photodissociation of nitric oxide plays an important role and the thermospheric NO abundance modulates the radiation field reaching the upper stratosphere. Perturbations in the nitric oxide concentration above the mesopause could therefore have an impact in the vicinity of the stratopause