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Background: Dyslipidemia is a known risk factor for cardiac dysfunction, and lipid-lowering therapy with statins reduces symptoms and reduces hospitalization related to left ventricular heart failure. Acute myocardial infarction (AMI) is a cause of morbidity and mortality worldwide. In this study, we aimed to determine the real-world AMI treatment drug combination used in Taiwan by using the NHI database to understand the treatment outcomes of current clinical medications prescribed for hyperlipidemia patients with AMI. Methods: Using the NHI Research Database (NHIRD), we conducted a retrospective cohort study that compared different treatments for AMI in hyperlipidemia patients in the period from 2016 to 2018. We compared the survival outcomes between those treated with and without organic nitrates in this cohort. Results: We determined that most hyperlipidemia patients were aged 61–70 y (29.95–31.46% from 2016 to 2018), and the annual AMI risk in these patients was <1% (0.42–0.68% from 2016 to 2018). The majority of hyperlipidemia patients with AMI were women, and 25.64% were aged 61–70 y. Receiving organic nitrates was associated with lower all-cause mortality rates (HR, 95% CI, p-value = 0.714, 0.674–0.756, p < 0.0001). After multivariate analysis, the overall survival in four groups (beta-blockers, beta-blocker + diuretics, diuretics, and others) receiving an organic nitrate treatment was significantly higher than in the groups that were not treated with organic nitrates (beta-blockers HR = 0.536, beta-blocker + diuretics HR = 0.620, diuretics HR = 0.715, and others HR = 0.690). Conclusions: The survival benefit was significantly greater in patients treated with organic nitrates than in those treated without organic nitrates, especially when combined with diuretics. A combination of organic nitrates could be a better treatment option for hyperlipidemia patients with AMI. [ABSTRACT FROM AUTHOR]

The role of anthropogenic NOx emissions in secondary organic aerosol (SOA) production is not fully understood but is important for understanding the contribution of emissions to air quality. Here, we examine the role of organic nitrates (RONO2) in SOA formation over the Korean Peninsula during the Korea-United States Air Quality field study in Spring 2016 as a model for RONO2 aerosol in cities worldwide. We use aircraft-based measurements of the particle phase and total (gas + particle) RONO2 to explore RONO2 phase partitioning. These measurements show that, on average, one-fourth of RONO2 are in the condensed phase, and we estimate that ≈15% of the organic aerosol (OA) mass can be attributed to RONO2. Furthermore, we observe that the fraction of RONO2 in the condensed phase increases with OA concentration, evidencing that equilibrium absorptive partitioning controls the RONO2 phase distribution. Lastly, we model RONO2 chemistry and phase partitioning in the Community Multiscale Air Quality modeling system. We find that known chemistry can account for one-third of the observed RONO2, but there is a large missing source of semivolatile, anthropogenically derived RONO2. We propose that this missing source may result from the oxidation of semi- and intermediate-volatility organic compounds and/or from anthropogenic molecules that undergo autoxidation or multiple generations of OH-initiated oxidation.

Understanding the size distribution, variation patterns, and potential formation mechanisms of particulate organic nitrates (PONs) is crucial for assessing their influences on atmospheric chemistry, air quality, and the regional climate. This study investigates PONs in the coastal atmosphere of Qingdao, China by collecting size-resolved particulate matter samples and analyzing six types of organic nitrates, namely pinene keto nitrate (PKN229), monoterpene hydroxyl nitrate (MHN215), monoterpene dicarbonyl nitrate (MDCN247), oleic acid hydroxyl nitrate (OAHN361), oleic acid keto nitrate (OAKN359), and pinene sulfate organic nitrate (PSON295), using ultrahigh-performance liquid chromatography(mass spectrometry). The mean total concentration of organic nitrates in fine particles reaches 677 ng m−3. The predominant compound is MHN215, followed by PKN229 and MDCN247. All six organic nitrates exhibited distinct concentration peaks in the droplet mode, with MDCN247 and OAHN361 showing a minor peak in the condensation mode. In addition, an apparent concentration peak is observed in the coarse mode for OAKN359. Comparative analyses under various conditions highlight the significant influences of primary emissions and secondary formation processes on the abundance and size distribution of organic nitrates. For instance, both firework displays during festivals and high NOx emissions from fuel combustion significantly increase the concentrations of condensation-mode organic nitrates, whereas dust particles enhanced the heterogeneous formation of coarse-mode particles. Furthermore, the high humidity of the coastal area promotes aqueous formation in droplet-mode particles. [ABSTRACT FROM AUTHOR]

Particulate secondary organic nitrates play a key role in understanding secondary organic aerosol production, ozone formation, and the atmospheric nitrogen cycle. However, the formation of particulate secondary organic nitrates in ambient air remains poorly understood. In this study, the nighttime formation processes of particulate secondary organic nitrates were investigated based on size‐resolved aerosols measured in urban air of China with a soot particle long‐time‐of‐flight aerosol mass spectrometer. The results show a bimodal size distribution of particulate secondary organic nitrates, peaking at ∼350 nm in condensation mode (100–400 nm) and ∼750 nm in droplet mode (400–2,500 nm), respectively. The nighttime formation processes of particulate secondary organic nitrates in the two size modes were respectively governed by temperature‐dependent condensation and aqueous‐phase processing. In particular, the mass concentration of particulate secondary organic nitrates in condensation mode was positively correlated with nitrate radical production and negatively correlated with temperature, suggesting that the formation processes were associated with the gas‐particle conversion of nitrate radical oxidation products. In contrast, the enhanced particulate secondary organic nitrates in droplet mode were predominantly contributed by aqueous‐phase processing, as indicated by the strong positive correlation with aerosol liquid water content and typical fragment ions from aqueous processing products (r = 0.52–0.59, P < 0.01). Our results highlight the potential of a size‐dependent mechanism to elucidate the formation processes of particulate secondary organic nitrates. Plain Language Summary: Particulate organic nitrates are an important nitrogen‐containing compound in the ambient atmosphere and have significant effects on air quality. However, the formation processes of particulate organic nitrates are complex in ambient air, leading to difficulties in understanding of their atmospheric processes and impacts. Here, nighttime formation of particulate secondary organic nitrates in different size particles is investigated in urban air. The results show that the nighttime formation pathways of particulate secondary organic nitrates in different size particles are distinct. Furthermore, aqueous processing plays an important role in the nighttime formation of particulate secondary organic nitrates in large size particles, especially in fog‐rain days. This information provides for a better understanding of the formation of particulate secondary organic nitrates in ambient air and is useful for future design of laboratory and atmospheric chemistry model studies. Key Points: Particulate secondary organic nitrates concentrations were significantly enhanced during fog‐rain days compared to non‐fog‐rain daysSize distributions of secondary organic nitrates were characterized by bimodal structure, peaking at ∼350 and ∼750 nm, respectivelyThe nighttime formation of organic nitrates in two size modes was respectively dominated by gas‐particle partitioning and aqueous processing [ABSTRACT FROM AUTHOR]

Organic nitrates contribute significantly to the total organic aerosol burden. However, the formation and loss mechanisms of particulate organic nitrates (PONs) remain poorly understood. In this study, with the CMAQ modeling system, we implement a detailed biogenic volatile organic carbon gas phase oxidation mechanism and an explicit representation of multiphase organic nitrate formation and loss, including both aqueous-phase uptake and vapor-pressure driven partitioning into organic aerosol as well as condensed-phase reactions. We find vapor-pressure dependent partitioning is the leading mechanism for formation of PONs and hydrolysis is a major loss mechanism for PON resulting in substantial amounts of organic aerosol that originate as an organic nitrate. Partitioning and hydrolysis together can produce high concentrations (up to 5 μg/m3) of PON-derived aerosols over the southeast United States. The main source of PON-derived aerosols is monoterpene nitrates that have been chemically processed to lose their nitrate functionality through aqueous chemistry. In contrast, the major portion of aqueous aerosol and in-cloud PON, which retains its nitrate moiety, are soluble isoprene nitrates. We evaluate the model using the observations from the Southern Oxidant and Aerosol Study (SOAS) campaign in the Southeast US in summer 2013 and show implementing aerosol-phase pathways for organic nitrates dramatically improves the magnitude of total alkyl nitrates (ANs) in CMAQ. The contribution of PONs to the total ANs at the SOAS site is estimated to be ~20%, a value in the range of the measurements. The predicted AN composition is shifted from monoterpene to isoprene and anthropogenic organic nitrates.

Background: The therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. Hemoglobin tightly binds to NO forming methemoglobin altering the erythrocytic antioxidant defense system. Aim: The principal objective of our research is to show the ameliorating effect of l-ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs used in cardiovascular diseases such as oxidative stresses and tolerance. Method: We studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered different concentrations of Isosorbide-5-mononitrate (ISMN) 0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg. Afterwards, we evaluated the role of l-ascorbic acid against these biochemical changes in cardiac tissues. Results: Chronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of the pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in the myocardium muscles in a dose-dependent manner. Meanwhile, such exposure caused a decline in the enzymatic effect of SOD, GSH and CAT accompanied by a decrease in the level of mitochondrial oxidative stress marker (nrf2) in the myocardium muscles and a decrease in the serum iron and total iron-binding capacity (TIBC) in a dose-dependent manner. Concomitant treatment with l-ascorbic acid significantly diminished these changes for all examined parameters. Conclusion: Chronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to the generation of reactive oxygen species. Using l-ascorbic acid can effectively ameliorate such intoxication to overcome nitrate tolerance.

Organic nitrates are widely used, but their chronic efficacy is blunted due to the development of tolerance. The properties of new tolerance free organic nitrates were studied. Their lipophilicity profile and passive diffusion across polydimethylsiloxane membrane and pig ear-skin, and their efficacy in tissue regeneration using HaCaT keratinocytes were evaluated. The permeation results show that these nitrates have a suitable profile for NO topical administration on the skin. Furthermore, the derivatives with higher NO release exerted a pro-healing effect on HaCaT cells. This new class of organic nitrates might be a promising strategy for the chronic treatment of skin pathologies. [ABSTRACT FROM AUTHOR]

Organic nitrates are broadly applied as pharmaceuticals (acting as efficient nitric oxide donor), energetic materials, building blocks in organic synthesis, etc. However, practical and direct methods to access organic nitrates efficiently are still rare, mainly due to the lack of powerful nitrooxylating reagents. Herein, we report bench‐stable and highly reactive noncyclic hypervalent iodine nitrooxylating reagents, oxybis(aryl‐λ3‐iodanediyl) dinitrates (OAIDNs, 2), which are prepared just by using aryliodine diacetate and HNO3. The reagents are used to achieve a mild and operationally simple protocol to access diverse organic nitrates. By employing of 2, zinc‐catalyzed regioselective nitrooxylation of cyclopropyl silyl ethers is realized efficiently to access the corresponding β‐nitrooxy ketones with high functional‐group tolerance. Moreover, a series of direct and catalyst‐free nitrooxylations of enolizable C−H bonds are carried out smoothly to afford the desired organic nitrates within minutes by just mixing the substrates with 2 in dichloromethane. [ABSTRACT FROM AUTHOR]

[Display omitted] The therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid peroxidation inside the red blood cells (RBCs) occur. Hemoglobin tightly binds to NO forming methemoglobin altering the erythrocytic antioxidant defense system. The principal objective of our research is to show the ameliorating effect of l -ascorbic acid for the deleterious effects of chronic administration of nitrovasodilator drugs used in cardiovascular diseases such as oxidative stresses and tolerance. We studied some biochemical parameters for the oxidative stress using groups of high sucrose/fat (HSF) diet Wistar male rats chronically orally administered different concentrations of Isosorbide-5-mononitrate (ISMN) 0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg. Afterwards, we evaluated the role of l -ascorbic acid against these biochemical changes in cardiac tissues. Chronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation, hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation, the cellular levels of the pro-inflammatory cytokines marker (NF-κB) and apoptosis markers (caspase-3) in the myocardium muscles in a dose-dependent manner. Meanwhile, such exposure caused a decline in the enzymatic effect of SOD, GSH and CAT accompanied by a decrease in the level of mitochondrial oxidative stress marker (nrf2) in the myocardium muscles and a decrease in the serum iron and total iron-binding capacity (TIBC) in a dose-dependent manner. Concomitant treatment with l -ascorbic acid significantly diminished these changes for all examined parameters. Chronic administration of organic nitrates leads to the alteration of the level of oxidative stress factors in the myocardium tissue due to the generation of reactive oxygen species. Using l -ascorbic acid can effectively ameliorate such intoxication to overcome nitrate tolerance. [ABSTRACT FROM AUTHOR]

Secondary organic aerosol (SOA) constitutes a substantial fraction of fine particulate matter and has important impacts on climate and human health. The extent to which human activities alter SOA formation from biogenic emissions in the atmosphere is largely undetermined. Here, we present direct observational evidence on the magnitude of anthropogenic influence on biogenic SOA formation based on comprehensive ambient measurements in the southeastern United States (US). Multiple high-time-resolution mass spectrometry organic aerosol measurements were made during different seasons at various locations, including urban and rural sites in the greater Atlanta area and Centreville in rural Alabama. Our results provide a quantitative understanding of the roles of anthropogenic SO2 and NOx in ambient SOA formation. We show that isoprene-derived SOA is directly mediated by the abundance of sulfate, instead of the particle water content and/or particle acidity as suggested by prior laboratory studies. Anthropogenic NOx is shown to enhance nighttime SOA formation via nitrate radical oxidation of monoterpenes, resulting in the formation of condensable organic nitrates. Together, anthropogenic sulfate and NOx can mediate 43-70% of total measured organic aerosol (29-49% of submicron particulate matter, PM1) in the southeastern US during summer. These measurements imply that future reduction in SO2 and NOx emissions can considerably reduce the SOA burden in the southeastern US. Updating current modeling frameworks with these observational constraints will also lead to more accurate treatment of aerosol formation for regions with substantial anthropogenic-biogenic interactions and consequently improve air quality and climate simulations.

Recent studies have highlighted the increased occurrence of reactive chlorine, drawing significant attention to the process of chlorinated chemical oxidation of oxygenated aromatics emitted from biomass burning (BB) in the formation of secondary organic aerosols (SOA). This study selected an oxygenated aromatic, anisole, as a representative of BB, and investigated the products and mechanisms of its reaction with Cl•, as well as exploring the implications of precursor-to-oxidant ratio ([anisole/Cl 2 ] 0), NOx levels, and seed particles on SOA generation. The gas-phase composition, SOA composition, and particle information were determined using a single-photon ionization time-of-flight mass spectrometry (SPIMS), a thermal desorption unit gas chromatography mass spectrometry (TDU-GC/MS), and a scanning mobility particle sizer (SMPS), respectively. Experimental results indicate that within minutes of turning on the ultraviolet (UV) lights, a large quantity of ultrafine particles (UFPs) (diameter <100 nm) is immediately formed. The SOA yield is significantly dependent on [anisole/Cl 2 ] 0 , decreasing from 66.2% to 20.0% as the [anisole/Cl 2 ] 0 increases. Upon oxidation by Cl•, anisole promptly released organic chlorides, including 2-chlorophenol and 2,4,6-trichlorophenol. The addition of NOx decreased the SOA yield, enhanced the role of OH• in the reaction process, and led to the formation of organic nitrogen products, such as C 6 H 5 NO 3 and C 7 H 7 NO 4. Furthermore, Cl• primarily initiates reactions through H-abstraction and Cl-substitution, resulting in the oxidation products largely retaining the benzene ring. This provides a potential explanation for the high SOA yield induced by Cl• in this study. Overall, our work suggests that the release of UFPs and organic chlorides can be found in the Cl-initiated oxidation of anisole, which contributes to high SOA yields. Against the backdrop of increasing wildfire frequency due to global warming, it is necessary to consider the contributions and sources of UFPs and organic chlorides caused by the reaction of wildfire emissions with Cl atoms. [Display omitted] • The generation of SOA from the reaction of Cl.• with anisole is highly effective. • The Cl-initiated oxidation of anisole causes the explosive formation of ultrafine particles and the release of organic chlorides. • High levels of NOx hindered the SOA yield in the anisole-Cl reaction system and enhanced the formation of organic nitrates. • Seed particles reduced the SOA yield, with inorganic seeds inhibiting NPF and organic seeds hardly forming new particles. [ABSTRACT FROM AUTHOR]

Background and Purpose: Organic nitrates such as nitroglycerin (NTG) or pentaerythritol tetranitrate (PETN) have been used for over a century in the treatment of angina or ischaemic heart disease. These compounds are prodrugs which release their nitrovasodilators upon enzymic bioactivation by aldehyde dehydrogenase (ALDH2) or cytochromes P450 (CYP). Whereas ALDH2 is known to directly activate organic nitrates in vessels, the contribution of vascular CYPs is unknown and was studied here.Experimental Approach: As all CYPs depend on cytochrome P450 reductase (POR) as electron donor, we generated a smooth muscle cell-specific, inducible knockout mouse of POR (smcPOR-/- ) to investigate the contribution of POR/CYP to vascular biotransformation of organic nitrates.Key Results: Microsomes containing recombinant CYPs expressed in human vascular tissues released nitrite from NTG and PETN with CYP2C9 and CYP2C8 being most efficient. SFK525, a CYP suicide inhibitor, blocked this effect. smcPOR-/- mice exhibited no obvious cardiovascular phenotype (normal cardiac weight and endothelium-dependent relaxation) and plasma and vascular nitrite production was similar to control (CTL) animals. NTG- and PETN-induced relaxation of isolated endothelium-intact or endothelium-denuded vessels were identical between CTL and smcPOR-/- . Likewise, nitrite release from organic nitrates in aortic rings was not affected by deletion of POR in smooth muscle cells (SMCs). In contrast, inhibition of ALDH2 by benomyl (10 μM) inhibited NTG-induced nitrite production and relaxation. Deletion of POR did not modulate this response.Conclusions and Implications: Our data suggest that metabolism by vascular CYPs does not contribute to the pharmacological function of organic nitrates. [ABSTRACT FROM AUTHOR]

A new field instrument is described that quantifies total particle phase organic nitrates. The instrument is based on the thermal dissociation laser induced fluorescence (TD-LIF) method that thermally converts nitrates to NO2 which is then detected by LIF. This instrument is unique in its ability to provide fast sensitive measurements of particle phase organic nitrates, without interference from inorganic nitrate. Here we use it to quantify organic nitrates in SOA generated from high-NOx photooxidation of limonene, a-pinene, D-3-carene, and tridecane. In these experiments the organic nitrate moiety is observed to be 6-15percent of the total SOA mass, depending on the organic precursor.

Rationale: Development and progression of cardiovascular diseases, including hypertension, are often associated with impaired nitric oxide synthase (NOS) function and nitric oxide (NO) deficiency. Current treatment strategies to restore NO bioavailability with organic nitrates are hampered by undesirable side effects and development of tolerance. In this study, we evaluated NO release capability and cardiovascular effects of the newly synthesized organic nitrate 1, 3-bis (hexyloxy) propan-2-yl nitrate (NDHP). Methods: A combination of in vitro and in vivo approaches was utilized to assess acute effects of NDHP on NO release, vascular reactivity and blood pressure. The therapeutic value of chronic NDHP treatment was assessed in an experimental model of angiotensin II-induced hypertension in combination with NOS inhibition. Results: NDHP mediates NO formation in both cell-free system and small resistance arteries, a process which is catalyzed by xanthine oxidoreductase. NDHP-induced vasorelaxation is endothelium independent and mediated by NO release and modulation of potassium channels. Reduction of blood pressure following acute intravenous infusion of NDHP was more pronounced in hypertensive rats (two-kidney-one-clip model) than in normotensive sham-operated rats. Toxicological tests did not reveal any harmful effects following treatment with high doses of NDHP. Finally, chronic treatment with NDHP significantly attenuated the development of hypertension and endothelial dysfunction in rats with chronic NOS inhibition and angiotensin II infusion. Conclusion: Acute treatment with the novel organic nitrate NDHP increases NO formation, which is associated with vasorelaxation and a significant reduction of blood pressure in hypertensive animals. Chronic NDHP treatment attenuates the progression of hypertension and endothelial dysfunction, suggesting a potential for therapeutic applications in cardiovascular disease.

Organic nitrates (RONO2) are an important NOx sink. In warm, rural environments dominated by biogenic emissions, nocturnal NO3‐initiated production of RONO2 is competitive with daytime OH‐initiated RONO2 production. However, in urban areas, OH‐initiated production of RONO2 has been assumed dominant and NO3‐initiated production considered negligible. We show evidence for nighttime RONO2 production similar in magnitude to daytime production during three aircraft campaigns in chemically distinct summertime environments: Studies of Emissions and Atmospheric Composition, Clouds, and Climate Coupling by Regional Surveys (SEAC4RS) in the rural Southeastern United States, Front Range Air Pollution and Photochemistry Experiment (FRAPPÉ) in the Colorado Front Range, and Korea‐United States Air Quality Study (KORUS‐AQ) around the megacity of Seoul. During each campaign, morning observations show RONO2 enhancements at constant, near‐background Ox (≡ O3+NO2) concentrations, indicating that the RONO2 are from a non‐photochemical source, whereas afternoon observations show a strong correlation between RONO2 and Ox resulting from photochemical production. We show that there are sufficient precursors for nighttime RONO2 formation during all three campaigns. This evidence impacts our understanding of nighttime NOx chemistry. Plain Language Summary: Nitrogen oxides are pollutants emitted during combustion which are involved in ozone and secondary aerosol production. One way in which nitrogen oxides are removed from the atmosphere is via chemistry that converts them to organic nitrates. This conversion of nitrogen oxides to organic nitrates has been thought to occur primarily during the day when the chemistry is driven by sunlight. Here we show evidence that nighttime processes generate similar quantities of organic nitrates to those produced by sunlight‐driven processes. Key Points: We show evidence for nocturnal production of organic nitrates similar in magnitude to daytime photochemical productionSignificant nocturnal production of organic nitrates observed from three aircraft campaigns in distinct environmentsNighttime production of organic nitrates impacts our understanding of the nighttime lifetime and fate of NOx [ABSTRACT FROM AUTHOR]

Chronic use of glyceryl trinitrate (GTN) is limited by serious side effects, such as tolerance and endothelial dysfunction of coronary and resistance arteries. Although GTN is used as a drug since more than 130 years, the mechanisms of the vasodilatory effects and of tolerance development to organic nitrates are still incompletely elucidated. New synthesized organic nitrates with and without antioxidant properties were characterized for their ex vivo tolerance profile, in order to investigate the oxidative stress hypothesis of nitrate tolerance. The organic nitrates studied showed different vasodilation and tolerance profiles, probably due to the ability or inability of the compounds to interact with the aldehyde dehydrogenase-2 enzyme (ALDH-2) involved in bioactivation. Furthermore, nitrooxy derivatives endowed with antioxidant properties did not determine the onset of tolerance, even if bioactivated by ALDH-2. The results of this study could be further evidence of the involvement of ALDH-2 in the development of nitrate tolerance. Moreover, the behavior of organic nitrates with antioxidant properties supports the hypothesis of the involvement of ROS in inactivating ALDH-2.

Glyceryl trinitrate (GTN) is one of the earliest known treatments for angina with a fascinating history that bridges three centuries. However, despite its central role in the nitric oxide (NO) story as a NO-donating compound, establishing the precise mechanism of how GTN exerts its medicinal benefit has proven to be far more difficult. This review brings together the explosive and vasodilatory nature of this three-carbon molecule while providing an update on the likely in vivo pathways through which GTN, and the rest of the organic nitrate family, release NO, nitrite, or a combination of both, while also trying to explain nitrate tolerance. Over the last 20 years the alcohol detoxification enzyme, aldehyde dehydrogenase (ALDH), has undoubtedly emerged as the front runner to explaining GTN’s bioactivation. This is best illustrated by reduced GTN efficacy in subjects carrying the single point mutation (Glu504Lys) in ALDH, which is also responsible for alcohol intolerance, as characterized by flushing. While these findings are significant for anyone following the GTN story, they appear particularly relevant for healthcare professionals, and especially so, if administering GTN to patients as an emergency treatment. In short, although the GTN puzzle has not been fully solved, clinical study data continue to cement the importance of ALDH, as uncovered in 2002, as a key GTN activator.

In this report, we describe the synthesis and characterization of 1,3-bis(hexyloxy)propan-2-yl nitrate (NDHP), a novel organic mono nitrate. Using purified xanthine oxidoreductase (XOR), chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy, we found that XOR catalyzes nitric oxide (NO) generation from NDHP under anaerobic conditions, and that thiols are not involved or required in this process. Further mechanistic studies revealed that NDHP could be reduced to NO at both the FAD and the molybdenum sites of XOR, but that the FAD site required an unoccupied molybdenum site. Conversely, the molybdenum site was able to reduce NDHP independently of an active FAD site. Moreover, using isolated vessels in a myograph, we demonstrate that NDHP dilates pre-constricted mesenteric arteries from rats and mice. These effects were diminished when XOR was blocked using the selective inhibitor febuxostat. Finally, we demonstrate that NDHP, in contrast to glyceryl trinitrate (GTN), is not subject to development of tolerance in isolated mesenteric arteries.

Organic nitrates formed from nighttime reaction between anthropogenic nitrate radicals (NO3) and biogenic volatile organic compounds (BVOCs) are an important but highly uncertain source of secondary organic aerosol (SOA). Here we report on the enhanced nighttime biogenic SOA formation observed in a polluted residual layer over Sacramento, California, the morning of 15 June 2010 during the Carbonaceous Aerosols and Radiative Effects Study (CARES). Trajectory analysis showed that the residual layer air, containing isoprene and trace amounts of monoterpenes left over after nighttime oxidation, was influenced by the San Francisco Bay Area emissions the previous evening. The residual layer aerosol was also enriched in nitrate, with about 64% of it estimated to be in the form of organic nitrates. The nitrate:organic mass ratio of the SOA was about 0.47 ± 0.044, which corresponds to the range typically found in isoprene mononitrates. Assuming the SOA was composed of organic mononitrates, its nominal molecular weight was estimated at 186 ± 11 g mol−1, consistent with the highly functionalized isoprene hydroxynitrates that have been observed in the particle phase in the southeast United States. Overall, our findings show that the efficiency of nighttime biogenic SOA formation, expressed as the change in organic aerosol mass relative to carbon monoxide (∆OA/∆CO), equals ~100 μg m−3 ppmv and is comparable to the range previously estimated for enhanced daytime SOA formation from mixed anthropogenic and biogenic emissions during CARES. Assuming the SOA was formed from isoprene oxidation by NO3, we estimated mass yields of up to 0.55, consistent with previous field estimates. Key Points: Airborne observations of trace gases and aerosol in a polluted residual layer over Sacramento, California, are analyzedNighttime secondary organic aerosol formation from mixed biogenic and anthropogenic emissions is as efficient as daytime productionThe estimated nitrate:organic mass ratio and molecular weight are consistent with those for highly functionalized isoprene hydroxynitrates [ABSTRACT FROM AUTHOR]

Organic nitrates in the atmosphere are associated with photochemical pollution and are the main components of secondary organic aerosols, which are related to haze. An efficient method for determining organic nitrates in atmospheric fine particles (PM2.5) was established using synthesized standards. Four alkyl (C7–C10) nitrates and three aromatic nitrates (tolyl nitrate, phenethyl nitrate, and p-xylyl nitrate) were synthesized and characterized by 1H and 13C nuclear magnetic resonance spectroscopy. The optimal ions for quantifying and confirming the identities of the analytes were identified by analyzing the standards by gas chromatography tandem mass spectrometry. The tandem mass spectrometer was a triple quadrupole instrument. This method can obtain more accurate information of organic nitrates than on-line methods. Spiked recovery tests were performed using three spike concentrations, and the recoveries were 61.0–111.4 %, and the relative standard deviations were < 8.2% for all of the analytes. Limits of detection and quantification were determined, and the linearity of the method for each analyte was assessed. The applicability of the method was demonstrated by analyzing six PM2.5 samples. Overall, 87% of the analytes were detected in the samples. Phenethyl nitrate, heptyl nitrate, and octyl nitrate were detected in every sample. Phenethyl nitrate was found at a higher mean concentration (3.23 ng/m3) than the other analytes. [ABSTRACT FROM AUTHOR]

Measurements of atmospheric dimethylsulfide (DMS), hydrogen sulfide (H2S), and carbon disulfide (CS2) were made over the North and South Atlantic Ocean as part of the Global Tropospheric Experiment/Chemical Instrumentation Test and Evaluation (GTE/CITE 3) project. DMS and CS2 samples were collected and analyzed using an automated gas chromatography/flame photometric detection system with a sampling frequency of 10 min. H2S samples were collected using silver nitrate impregnated filters and analyzed by fluorescence quenching. The DMS data from both hemispheres have a bimodal distribution. Over the North Atlantic this reflects the difference between marine and continental air masses. Over the South Atlantic it may reflect differences in the sea surface source of DMS, corresponding to different air mass source regions. The median boundary layer H2S and CS2 levels were significantly higher in the northern hemisphere than the southern hemisphere, reflecting the higher frequency of samples influenced by pollutant and/or coastal emissions. Composite vertical profiles of DMS and H2S are similar to each other, and are consistent with a sea surface source. Vertical profiles of CS2 have maxima in the free troposphere, implicating a continental source. The low levels of H2S and CS2 found in the southern hemisphere constrain the role of these compounds in global budgets to significantly less than previously estimated.

A major purpose of the third joint Soviet-American Gases and Aerosols (SAGA 3) oceanographic cruise was to examine remote tropical marine O3 and photochemical cycles in detail. On leg 1, which took place between Hilo, Hawaii, and Pago-Pago, American Samoa, in February and March 1990, shipboard measurements were made of O3, CO, CH4, nonmethane hydrocarbons (NMHC), NO, dimethyl sulfide (DMS), H2S, H2O2, organic peroxides, and total column O3. Postcruise analysis was performed for alkyl nitrates and a second set of nonmethane hydrocarbons. A latitudinal gradient in O3 was observed on SAGA 3, with O3 north of the intertropical convergence zone (ITCZ) at 15–20 parts per billion by volume (ppbv) and less than 12 ppbv south of the ITCZ but never ≤3 ppbv as observed on some previous equatorial Pacific cruises (Piotrowicz et al., 1986; Johnson et al., 1990). Total column O3 (230–250 Dobson units (DU)) measured from the Akademik Korolev was within 8% of the corresponding total ozone mapping spectrometer (TOMS) satellite observations and confirmed the equatorial Pacific as a low O3 region. In terms of number of constituents measured, SAGA 3 may be the most photochemically complete at-sea experiment to date. A one-dimensional photochemical model gives a self-consistent picture of O3-NO-CO-hydrocarbon interactions taking place during SAGA 3. At typical equatorial conditions, mean O3 is 10 ppbv with a 10–15% diurnal variation and maximum near sunrise. Measurements of O3, CO, CH4, NMHC, and H2O constrain model-calculated OH to 9 × 105 cm−3 for 10 ppbv O3 at the equator. For DMS (300–400 parts per trillion by volume (pptv)) this OH abundance requires a sea-to-air flux of 6–8 × 109cm−2 s−1, which is within the uncertainty range of the flux deduced from SAGA 3 measurements of DMS in seawater (Bates et al., this issue). The concentrations of alkyl nitrates on SAGA 3 (5–15 pptv total alkyl nitrates) were up to 6 times higher than expected from currently accepted kinetics, suggesting a largely continental source for these species. However, maxima in isopropyl nitrate and bromoform near the equator (Atlas et al., this issue) as well as for nitric oxide (Torres and Thompson, this issue) may signify photochemical and biological sources of these species.

This paper reports results from NASA's Chemical Instrumentation and Test Evaluation (CITE 3) during which airborne measurements of dimethyl sulfide (DMS) from six instruments were intercompared. Represented by the six instruments are three fundamentally different detection principles (flame photometric, mass spectrometric, and electron capture after fluorination); three collection/preconcentration methods (cryogenic, gold wool absorption, and polymer absorbent); and three types of oxidant scrubbers (solid phase alkaline, aqueous reactor, and cotton). The measurements were made over the Atlantic Ocean in August/September 1989 during flights from NASA's Wallops Flight Center, Virginia, and Natal, Brazil. The majority of the intercomparisons are at DMS mixing ratios

The article tells about the pharmacology of nitrates and their place in comprehensive treatment of coronary artery disease. The mechanisms of action of organic nitrates, specifically the short-acting metered dose spray isosorbide dinitrate (ID), are demonstrated. Indications and contraindications for use in various forms of coronary artery disease are analyzed.

Abstract We performed continuous observations (2012–2015) of total peroxy nitrates (PNs) and total organic nitrates (ONs) at Suzu on the Noto peninsula, Japan. It was found that PNs and ONs showed similar seasonal variations with maximum concentrations in spring and minimum concentrations in summer. Concentrations of PNs and ONs were high for air masses originating from the Asian continent from winter to spring, whereas they were independent of air mass origin from spring to summer. In summer, PNs and ONs indicated similar diurnal variations with maximum concentrations during daytime and minimum concentrations during nighttime. Such diurnal variations of PNs and ONs were small in winter. Diurnal variations of PNs in spring were similar to those in summer, whereas such diurnal variations were not observed for ONs in spring. In the cold season, PNs and ONs have long atmospheric lifetimes and local photochemical production rates of PNs and ONs are slow, whereas the converse is true in the warm season. Therefore, concentration variations of PNs and ONs are governed primarily by long-range transport in the cold season and by local photochemical production in the warm season. Highlights • Continuous observations of PNs and ONs were performed at Noto Peninsula, Japan. • PNs and ONs showed characteristic seasonal and diurnal variations. • The main variable factor of PNs and ONs is long-range transport in the cold season. • PNs and ONs are influenced mainly by photochemical production in the warm season. [ABSTRACT FROM AUTHOR]

In this work, a systematic investigation of the atmospheric oxidation mechanism of (CF 3 ) 2 CXOCH 3 and their oxidative products (CF 3 ) 2 CXOCHO (X = H, F) initiated by OH radical or Cl atom is performed by density functional theory. This study reveals that the introduction of NO and O 2 promotes the formation of organic nitrates, which are hygroscopic and are inclined to form secondary organic aerosols (SOA) and can affect the air quality. The rate constants of the individual reactions are found to be in agreement with the experimental results. One of the intriguing findings of this work is that the peroxynitrite of (CF 3 ) 2 CHOCH 2 OONO formed from the subsequent reactions of (CF 3 ) 2 CHOCH 3 is more favorable to isomerize to organic nitrate (CF 3 ) 2 CHOCH 2 ONO 2 than to dissociate into alkoxy radical (CF 3 ) 2 CHOCH 2 O and NO 2 because of the lower energy barrier of isomerization. The second significant observation is that the organic nitrate can be degraded more favorably with the presence of NH 3 , CH 3 NH 2 , and CH 3 NHCH 3 than its naked decomposition reaction (CF 3 ) 2 CHOCH 2 ONO 2 →(CF 3 ) 2 CHOCHO + HONO. The ammonium salt, a vital part of haze, is harmful to human health and can be formed in the existence of the NH 3 , CH 3 NH 2 , and CH 3 NHCH 3 . In addition, the toxic substance of peroxyalkyl nitrate (CF 3 ) 2 CHOC(O)ONO 2 which can reduce the visibility of the atmosphere is produced as the primary subsequent oxidation product of (CF 3 ) 2 CHOCHO in a NO-rich environment. The main species detected experimentally are confirmed by this study. The computational results are crucial to risk assessment and pollution prevention of the volatile organic compounds (VOCs). [ABSTRACT FROM AUTHOR]

Aim. To compare antianginal and antiischemic efficacy and tolerability of buccal nitroglycerine – Trinotrolong (TNL) medication and most commonly used pills of isosorbide-5-mononitrate (I5M) and isosorbide dinitrate (ID) in patients with stable angina.Material and methods. The study is multicenter, randomized, openlabel. Totally 71 pt studied, mean age 59,5±4,3 y., with not less than three angina episodes (AEp) per week at the background of usual physical activity and positive exercise stress test on tread-mill (EST). After randomization all patients were taking by the cross-method the TNL 4-8 mg/day “on demand” and I5M or ID 40 mg/day during next 6 weeks each. Efficacy of the drugs was assessed by the method of repeated EST, quantity of AEp and pill (dosages) taken of the short-acting nitroglycerine.Results. All medications studied led to a significant relevant increase of the threshold exertion duration as at the 1st day of intake (coupled TNL), as during regular intake. In contrast to TNL and I5M, regular intake of ID led to relevant decrease of the threshold exertion duration comparing to the 1st day of its intake (p=0,04), that witnessed for tolerance. At the background of all medications studied, there was relevant decrease of AEp per week and of long-acting nitrates intake, without significant differences between drugs. There were no any significant differences in the prevalence of side effects, of those – the most often headache occurred with slight decrease with the continuous intake.Conclusion. Significant stable antianginal and antiischemic efficacy of TNL is achieved by transmucous load of buccal nitroglycerine into the body, fast effect development, its prolongation, that makes possible to use TNL by the “on demand” schedule, just before the expected physical and emotional activity.

Organic nitrates are secondary atmospheric pollutants that play a key role in ozone and aerosol production. This study focused on the simulation of organic nitrates through a box model coupled with RACM2 (Regional Atmospheric Chemistry Mechanism, version 2), based on data from the PRIDE-PRD2006 campaign in Backgarden, China. Our study found that an overestimation of organic nitrate production rate was generated by the model. Furthermore, the effective production ratio (α) of organic nitrates was around 0.033 after optimizing its chemical production module. The chemical impacts of organic nitrates on ozone production were related to VOC-OH reactivity and α. We found that VOC-OH reactivity was positively related to α, resulting in the suppression of ozone production caused by organic nitrates, which showed that P(O=O+NO) increased initially and subsequently decreased with VOC-OH reactivity. These results highlight the importance of organic nitrate's impact on ozone production in strategies to control ozone pollution, specifically regarding the reduction of low-molecular-weight VOCs in the Pearl River Delta. [ABSTRACT FROM AUTHOR]

Background/Aims: 2-aminoethyl nitrate (CLC-1011) is a member of the class of organic nitrates that cause vasodilation by the generation of nitric oxide (•NO). These drugs are mainly used for the treatment of angina pectoris and ischemic heart disease. The aim of this study was to characterize the vasodilatory potency of this organic nitrate alone and in combination with clinically established cardiovascular drugs. Methods: Vasodilation by CLC-1011 was tested by isometric tension studies, either alone or combined with cilostazol, valsartan, and metoprolol. Induction of oxidative stress in isolated heart mitochondria was measured by enhanced chemiluminescence. Bioactivation of CLC-1011 in aortic tissue was measured by electron paramagnetic resonance spectroscopy using an iron-based spin trap for •NO. Results: We observed potent vasodilation by CLC-1011 and additive effects for all three drug combinations. In contrast to nitroglycerin (GTN), CLC-1011 did not stimulate mitochondrial oxidative stress. CLC-1011 was bioactivated to •NO in aortic tissue. Conclusion: In summary, the experiments described in this report demonstrate that CLC-1011 does not induce oxidative stress, is a more potent vasodilator than isosorbide-5-mononitrate and dinitrate ISDN, and displays synergistic vasodilation with other cardiovascular drugs. CLC-1011 fixed dose combinations could be used in the management of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

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A variety of new energetic compounds were synthesized with the tris(hydroxymethyl)aminomethane (Tris) moiety as a building block. The new nitrates were fully characterized, with use of multinuclear NMR spectroscopy, vibrational analysis, mass spectrometry, differential scanning calorimetry, and elemental analysis. The structure of each compound was confirmed by single-crystal X-ray diffraction. The energies of forma-tion were calculated with the Gaussian program package, and the detonation parameters were predicted by using the EXPLO5 computer code. Because of the positive oxygen balance (ΩCO) of the presented compounds, their performance data as oxidizers were compared to the common oxidizer ammonium perchlorate. [ABSTRACT FROM AUTHOR]

Aromatic hydrocarbons are important contributors to the formation of ozone and secondary organic aerosols in urban environments. The different parallel pathways in aromatic oxidation, however, remain inadequately understood. Here, we investigated the production yields and chemical distributions of gas-phase tracer products during the photooxidation of alkylbenzenes at atmospheric OH levels with NO x present using high-resolution mass spectrometers. The peroxide-bicyclic intermediate pathway emerged as the major pathway in aromatic oxidation, accounting for 52.1 ± 12.6%, 66.1 ± 16.6%, and 81.4 ± 24.3% of the total OH oxidation of toluene, m-xylene, and 1,3,5-trimethylbenzene, respectively. Notably, the yields of bicyclic nitrates produced from the reactions of bicyclic peroxy radicals (BPRs) with NO were considerably lower (3-5 times) than what the current mechanism predicted. Alongside traditional ring-opening products formed through the bicyclic pathway (dicarbonyls and furanones), we identified a significant proportion of carbonyl olefinic acids generated via the 1,5-aldehydic H-shift occurring in subsequent reactions of BPRs + NO, contributing 4-7% of the carbon flow in aromatic oxidation. Moreover, the observed NO x -dependencies of ring-opening and ring-retaining product yields provide insights into the competitive nature of reactions involving BPRs with NO, HO 2 , and RO 2 , which determine the refined product distributions and offer an explanation for the discrepancies between the experimental and model-based results.

Thionitrates (RSNO2) have been proposed as key intermediates in the biotransformation of organic nitrates that have been used as nitric oxide prodrugs. However, thionitrates are usually very labile and model studies on the chemical processes involving thionitrates have been difficult. In this paper, model studies of biologically relevant chemical processes involving thionitrates by taking advantage of a nano-sized molecular cavity are summarized. [ABSTRACT FROM AUTHOR]

Semivolatile organic nitrates (SVONs) contribute a large proportion of total organic nitrates and play an important role in the tropospheric chemistry. However, the composition and concentrations of SVONs in the atmosphere remain unclear due to the lack of reliable analytical techniques for specific organic nitrates. In this study, a method based on gas chromatography and electron ionization⁻mass spectrometry was developed to detect ambient SVONs that were collected via polyurethane foam disk enrichment. Three SVONs were identified in the semivolatile samples from urban Jinan during spring based on the characteristic fragment ions of [NO2]+ and [CH2NO3]+ and the characteristic fragment loss of NO2 and NO3: 1-pentyl nitrate (molecular weight [MW] = 133), 4-hydroxy-isoprene nitrate (MW = 147), and (3,4)-di-hydroxy-isoprene nitrate (MW = 163). The latter two isoprene nitrates were rarely detected in the real atmosphere in previous studies. The contents of 1-pentyl nitrate, 4-hydroxy-isoprene nitrate, and (3,4)-di-hydroxy-isoprene nitrate were roughly quantified based on the standard of 1-pentyl nitrate, with a detection limit of 50 μg L−1. In addition, Fourier transform infrared spectrometry was used to determine the total SVONs content. The average concentrations of 1-pentyl nitrate, 4-hydroxy-isoprene nitrate, (3,4)-di-hydroxy-isoprene nitrate, and total SVONs in Jinan during spring were 20.2 ± 7.2, 13.2 ± 7.2, 36.5 ± 8.4, and 380.0 ± 190.8 ng m−3, respectively. The three identified SVONs contributed only 20.2 ± 5.5% to the total SVONs, which suggests that some unidentified SVONs are present in the ambient atmosphere and that studies with improved or advanced analytical techniques will be required to identify them.

The photochemical reaction of peroxy radical (RO 2 ·) and NO has been identified by field and forest studies as important source of organic nitrates (RONO 2) in the atmosphere. However, this traditional pathway is not sufficient to explain the high concentration of RONO 2. Hence, a new source of the tropospheric RONO 2 from the dark reactions of nitric acid (HNO 3) with aliphatic aldehydes (C 1 –C 5) under catalysis is provided and examined for the first time by high-level quantum chemistry. The findings show that the reaction between HCHO and HNO 3 , which produces HOCH 2 ONO 2 , can be catalyzed by a series of metal-free catalysts (NH 3 , CH 3 NH 2 , CH 3 NHCH 3 , H 2 O, HNO 3 , H 2 SO 4 , HCOOH, HOOCCOOH). At 296 K, the effective rate constant for the bimolecular HNO 3 –HCHO reaction under the catalysis of CH 3 NH 2 or CH 3 NHCH 3 can be sufficiently accelerated by 5–8 order of magnitudes through this new loss pathway for HNO 3 or HCHO to become competitive with the conventional loss pathway for their photochemical reactions with ·OH radical. Significantly, this new HOCH 2 ONO 2 formation pathway from the dark reaction of HCHO with CH 3 NH 3 +NO 3 −/(CH 3) 2 NH + NO 3 − was more favorable than the recognized source of RO 2 · with NO. Efficient catalysis performance of CH 3 NH 2 and CH 3 NHCH 3 is mainly attributed to their excellent proton receptivity capacity by activating the O–H bond of HNO 3 to form stable organic nitrates (CH 3 NH 3 +NO 3 − and (CH 3) 2 NH + NO 3 −) in the rate-determining step transition states. In the case of only considering the barrier, H 2 SO 4 is the best catalyst among the investigated inorganic and organic acids, and dicarboxylic acid (HOOCCOOH) is stronger than monocarboxylic acid HCOOH in facilitating the RONO 2 formation reaction. These new findings deepen our understanding on the unexpected source of organic nitrate and loss pathway of HNO 3 or HCHO under catalysis in highly polluted regions. [Display omitted] • Kinetics and mechanism for reactions of HNO 3 with C 1 –C 5 aliphatic aldehydes were studied. • Role of water, acids, and alkalies on the HNO 3 /HCHO reaction were analyzed. • A new loss pathway for HCHO was identified via amine-catalyzed HNO 3 /HCHO reaction. • An unexpected source of RONO 2 with the help of catalysts was proposed and verified. • The proposed new source of RONO 2 was more favorable than that of RO 2 ·/NO reaction. [ABSTRACT FROM AUTHOR]

Thionitrates (R-SNO2) have been proposed as key intermediates in the biotransformation of organic nitrates that have been used for the clinical treatment of angina pectoris for over 100 years. It has been proposed and widely accepted that a thiol would react with an organic nitrate to afford a thionitrate intermediate. However, there has been no example of an experimental demonstration of this elementary chemical process in organic systems. Herein, we report that aryl- and primary-alkyl-substituted thionitrates were successfully synthesized by the reaction of the corresponding lithium thiolates with organic nitrates by taking advantage of cavity-shaped substituents. The structure of a primary-alkyl-substituted thionitrate was unambiguously established by X-ray crystallographic analysis. [ABSTRACT FROM AUTHOR]