Nitric oxide : biology and chemistry最新文献

The literature is conflicting regarding salivary nitrite (NO₂⁻)/nitrite and nitrate (NO₂⁻ and NO₃⁻) levels in children affected by dental caries. For this reason, a systematic review to provide a consensus on the subject was propose, whose objective is to verify whether these molecules could be used as biomarkers in children with caries. A comprehensive search was performed on online database and eleven articles were included in the meta-analysis. The methodological quality of studies was assessed by Newcastle-Ottawa Scale recommended for case-control studies and by AXIS tool for cross-sectional studies. Grading of Recommendations Assessment, Development and Evaluation was used for the assessment of the certainty of the evidence for each outcome. The results showed lower NO₂⁻ levels in the group of children affected by dental caries (SMD = −2.18 [-3.24, −1.13], p < 0.01). Age, saliva collection and methods of evaluation can impact the results. When evaluating the severity of the condition, an important variation was detected in relation to the different evaluation methods NO₂⁻/NO₂⁻ and NO₃⁻. In conclusion, based on the evidence presented, the results suggest that NO₂⁻ levels in saliva are a possible biomarker of dental caries. Results should be evaluated with caution due to the very low evidence from primary studies. Longitudinal studies are necessary to strengthen this hypothesis.

The continuously rising prevalence of cardiovascular disease (CVD) globally substantially impacts the economic growth of developing countries. Indeed, one of the leading causes of death worldwide is unfavorable cardiovascular events. Reduced nitric oxide (NO) generation is the pathogenic foundation of endothelial dysfunction, which is regarded as the first stage in the development of a number of CVDs. Nitric oxide exerts an array of biological effects, including vasodilation, the suppression of vascular smooth muscle cell proliferation and the functional control of cardiac cells. Numerous treatment strategies aim to increase NO synthesis or upregulate downstream NO signaling pathways. The major component of Curcuma longa, curcumin, has long been utilized in traditional medicine to treat various illnesses, especially CVDs. Curcumin improves CV function as well as having important pleiotropic effects, such as anti-inflammatory and antioxidant, through its ability to increase the bioavailability of NO and to positively impact NO-related signaling pathways. In this review, we discuss the scientific literature relating to curcumin's positive effects on NO signaling and vascular endothelial function.

Whether endothelium derived Nitric Oxide (NO) uptake by the blood is limited by a boundary layer, the red cell membrane or its interior is the subject of continued debate. Whether lung uptake of NO in the single-breath D_LNO test is limited by blood or not is also debated. To understand which processes are limiting blood NO uptake we have modelled NO chemical kinetics and we have derived a shrinking core model, Thiele Modulus and FTCS (Euler) numerical solution. In a rapid reaction apparatus, NO uptake appears limited by a boundary layer, and throughout the red cell, by diffusion. In the single breath situation, and arguably with endogenous NO in vivo, NO uptake appears limited by a boundary layer and a pseudo first order chemical reaction in the outer molecular layers of the red cell. We have not found evidence to support red cell membrane limitation.

6-Nitrodopamine (6-ND) is released from rat and human vas deferens and is considered a major mediator of both tissues contractility. The contractions induced by 6-ND are selectively blocked by both tricyclic antidepressants and α₁-adrenoceptor antagonists. Endothelial nitric oxide synthase (eNOS) is the major isoform responsible for 6-ND release in mouse isolated heart, however the origin of 6-ND in the vas deferens is unknown. Here it was investigated by LC-MS/MS the basal release of 6-ND from isolated vas deferens obtained from control, eNOS^−/−, nNOS^−/−, and iNOS^−/− mice. In addition, it was evaluated in vitro vas deferens contractility following electric field stimulation (EFS).

Basal release of 6-ND was significantly reduced in nNOS^−/− mice compared to control mice, but not decreased when the vas deferens were obtained from either eNOS^−/− or iNOS^−/− mice. Pre-incubation of the vas deferens with tetrodotoxin (1 μM) significantly reduced the basal release of 6-ND from control, eNOS^−/−, and iNOS^−/− mice but had no effect on the basal release of 6-ND from nNOS^−/− mice. EFS-induced frequency-dependent contractions of the vas deferens, which were significantly reduced when the tissues obtained from control, eNOS^−/− and iNOS^−/− mice, were pre-incubated with l-NAME, but unaltered when the vas deferens was obtained from nNOS^−/− mice. In addition, the EFS-induced contractions were significantly smaller when the vas deferens were obtained from nNOS^−/− mice.

The results clearly demonstrate that nNOS is the main NO isoform responsible for 6-ND release in mouse vas deferens and reinforces the concept of 6-ND as a major modulator of vas deferens contractility.

This study explores the antiarrhythmic and hypotensive potential of pyridyl-substituted nitronyl nitroxides derivatives, uncovering the crucial role of a single carbon moiety of the pyridine cycle alongside radical and charged oxygen centers of the imidazoline fragment. Notably, the introduction of fluorine atoms diminished the antiarrhythmic effect, while the most potent derivatives featured the nitronyl nitroxide pattern positioned at the third site of the pyridine cycle. Gender-dependent responses were observed in lead compounds L^CF3 and L^Me, with L^Me inducing temporary bradycardia and hypotension specifically in female rats, and L^CF3 causing significant blood pressure reduction followed by rebound in females compared to milder effects in males. Mechanistic insights point towards β₁ adrenoceptor blockade as an underlying mechanism, supported by experiments on isolated rat atria. This research underscores the interplay between structure, cardiovascular effects and gender-specific responses, offering insights for therapeutic strategies for treating free radical-associated cardiovascular disorders.

Statin therapy is a cornerstone in the treatment of systemic vascular diseases. However, statins have failed to translate as therapeutics for pulmonary vascular disease. Early pulmonary vascular disease in the setting of congenital heart disease (CHD) is characterized by endothelial dysfunction, which precedes the more advanced stages of vascular remodeling. These features make CHD an ideal cohort in which to re-evaluate the potential pulmonary vascular benefits of statins, with a focus on endothelial biology. However, it is critical that the full gamut of the pleiotropic effects of statins in the endothelium are uncovered. The purpose of this investigation was to evaluate the therapeutic potential of simvastatin for children with CHD and pulmonary over-circulation, and examine mechanisms of simvastatin action on the endothelium. Our data demonstrate that daily simvastatin treatment preserves endothelial function in our shunt lamb model of pulmonary over-circulation. Further, using pulmonary arterial endothelial cells (PAECs) isolated from Shunt and control lambs, we identified a new mechanism of statin action mediated by increased expression of the endogenous Akt1 inhibitor, C-terminal modifying protein (CTMP). Increases in CTMP were able to decrease the Akt1-mediated mitochondrial redistribution of endothelial nitric oxide synthase (eNOS) which correlated with increased enzymatic coupling, identified by increases in NO generation and decreases in NOS-derived superoxide. Together our data identify a new mechanism by which simvastatin enhances NO signaling in the pulmonary endothelium and identify CTMP as a potential therapeutic target to prevent the endothelial dysfunction that occurs in children born with CHD resulting in pulmonary over-circulation.

Background

Endothelial-mesenchymal transition (EndMT) induced by low shear stress plays an important role in the development of atherosclerosis. However, little is known about the correlation between hydrogen sulfide (H₂S), a protective gaseous mediator in atherosclerosis and the process of EndMT.

Methods

We constructed a stable low-shear-stress-induced(2 dyn/cm²) EndMT model, acombined with the pretreatment method of hydrogen sulfide slow release agent(GYY4137). The level of MEST was detected in the common carotid artery of ApoE^−/− mice with local carotid artery ligation. The effect of MEST on atherosclerosis development in vivo was verified using ApoE^−/− mice were given tail-vein injection of endothelial-specific overexpressed and knock-down MEST adeno-associated virus (AAV).

Results

These findings confirmed that MEST is up-regulated in low-shear-stress-induced EndMT and atherosclerosis. In vivo experiments showed that MEST gene overexpression significantly promoted EndMT and aggravated the development of atherosclerotic plaques and MEST gene knockdown significantly inhibited EndMT and delayed the process of atherosclerosis. In vitro, H₂S inhibits the expression of MEST and EndMT induced by low shear stress and inhibits EndMT induced by MEST overexpression. Knockdown of NFIL3 inhibit the up regulation of MEST and EndMT induced by low shear stress in HUVECs. CHIP-qPCR assay and Luciferase Reporter assay confirmed that NFIL3 binds to MEST DNA, increases its transcription and H₂S inhibits the binding of NFIL3 and MEST DNA, weakening NFIL3's transcriptional promotion of MEST. Mechanistically, H₂S increased the sulfhydrylation level of NFIL3, an important upstream transcription factors of MEST. In part, transcription factor NFIL3 restrain its binding to MEST DNA by sulfhydration.

Conclusions

H₂S negatively regulate the expression of MEST by sulfhydrylation of NFIL3, thereby inhibiting low-shear-stress-induced EndMT and atherosclerosis.

Dietary nitrates (NO3-) are naturally occurring compounds in various vegetables, especially beetroot, which is mainly supplemented in the form of BRJ. Dietary nitrates (NO3-) play a crucial function in human physiology. On consumption, nitrates (NO3-) undergo a conversion process, producing nitric oxide (NO) via a complex metabolic pathway. Nitric oxide (NO) is associated with many physiological processes, entailing immune modulation, neurotransmission, and vasodilation, enabling blood vessel dilation and relaxation, which boosts blood flow and oxygen delivery to tissues, positively influencing cardiovascular health, exercise performance, and cognitive function. There are various analytical processes to determine the level of nitrate (NO3-) present in dietary sources. The impact of dietary nitrates (NO3-) can differ among individuals. Thus, the review revisits the dietary source of nitrates (NO3-), its metabolism, absorption, excretion, analytical techniques to assess nitrates (NO3-) content in various dietary sources, and discusses health effects.

Nitric oxide (NO) is a versatile signaling molecule that plays a crucial role in regulating postharvest fruit quality. The utilization of NO donors to elevate endogenous NO levels and induce NO-mediated responses represents a promising strategy for extending fruit shelf-life after harvest. However, the effectiveness of NO treatment is influenced by various factors, including formulation and application methods. In this review, we investigate the impact of NO supply on different fruits, aiming to prolong postharvest shelf-life and enhance fruit quality. Furthermore, we delve into the underlying mechanisms of NO action, particularly its interactions with ethylene and reactive oxygen species (ROS). Excitingly, we also highlight the emerging field of nanotechnology in postharvest applications, discussing the use of nanoparticles as a novel approach for achieving sustained release of NO and enhancing its effects. By harnessing the potential of nanotechnology, our review is a starting point to help identify gaps and future directions in this important, emerging field.

S-Nitroso-N-acetylpenicillamine (SNAP) is among the most common nitric oxide (NO)-donor molecules and its solid-state photolytic decomposition has potential for inhaled nitric oxide (iNO) therapy. The photochemical NO release kinetics and mechanism were investigated by exposing solid-state SNAP to a narrow-band LED as a function of nominal wavelength and intensity of incident light. The photolytic efficiency, decomposition products, and the photolytic pathways of the SNAP were examined. The maximum light penetration depth through the solid layer of SNAP was determined by an optical microscope and found to be within 100–200 μm, depending on the wavelength of light. The photolysis of solid-state SNAP to generate NO along with the stable thiyl (RS·) radical was confirmed using Electron Spin Resonance (ESR) spectroscopy. The fate of the RS· radical in the solid phase was studied both in the presence and absence of O₂ using NMR, IR, ESR, and UPLC-MS. The changes in the morphology of SNAP due to its photolysis were examined using PXRD and SEM. The stable thiyl radical formed from the photolysis of solid SNAP was found to be reactive with another adjacent thiyl radical to form a disulfide (RSSR) or with oxygen to form various sulfonyl and sulfonyl peroxyl radicals {RS(O)_xO·, x = 0 to 7}. However, the thiyl radical did not recombine with NO to reform the SNAP. From the PXRD data, it was found that the SNAP loses its crystallinity by generating the NO after photolysis. The initial release of NO during photolysis was increased with increased intensity of light, whereas the maximum light penetration depth was unaffected by light intensity. The knowledge gained about the photochemical reactions of SNAP may provide important insight in designing portable photoinduced NO-releasing devices for iNO therapy.