Effect of inhaled nitric oxide on endotoxin-induced hypoxaemia in rabbits

In five mechanically ventilated rabbits, we studied the property of inhaled nitric oxide in helping to treat hypoxaemia which was induced by intravenous endotoxin (Escherichiacoli-derived lipopolysaccharide, serotype 0111: B4). We used measurements of arterial partial pressure of oxygen to check a therapeutic nitric oxide benefit. Pulmonary artery pressure was continuously monitored. Furthermore, we determined the single-breath diffusing capacity for nitric oxide. Measurements of plasma nitrite/nitrate concentration served as an indicator of endogenous nitric oxide output. The first infusion of endotoxin led to a transient pulmonary vasoconstriction, whereas arterial partial pressure of oxygen was permanently reduced by 30 ± 10 mmHg (mean ± SD), attaining minimal values of 48 ± 3.4 mmHg due to additional endotoxin. Single-breath diffusing capacity for nitric oxide declined by 20 ± 5.5% of baseline values until the experiments were concluded. Endotoxin induced an increase in plasma nitrite/nitrate concentration in the five rabbits as well as in the control animals (four rabbits) without exogenous nitric oxide supply. During the 25 inhalations of nitric oxide (3–50 ppm), arterial oxygenation did not change significantly. Thus endotoxin permanently impaired pulmonary gas exchange without inducing pulmonary hypertension. Inhaled nitric oxide did not improve arterial oxygenation during endotoxaemia.     

Nitrite‐derived nitric oxide: a possible mediator of ‘acidic–metabolic’ vasodilation

The fundamental, yet poorly understood, physiological mechanism known as ‘acidic–metabolic’ vasodilation, contributes to local blood flow regulation during hypoxia/ischaemia and increased metabolic activity. The vasodilator nitric oxide (NO) has been suggested to be involved in this event. Besides enzymatic production by NO synthases, a novel mechanism for generation of this gas in vivo was recently described. This involves non‐enzymatic reduction of inorganic nitrite to NO, a reaction that takes place predominantly during acidic/reducing conditions. We have studied the effects of physiological amounts of nitrite on NO generation and relaxation of rat aorta in vitro in a situation where environmental pH was reduced to levels seen in tissues during hypoxia/ischaemia. The relaxatory effect of nitrite was increased in an acidic buffer solution (pH 6.6) compared with neutral pH; EC50 for nitrite was reduced from 200 to 40 μM . Nitrite‐evoked relaxation was effectively prevented by coadministration of an inhibitor of soluble guanylyl cyclase. The relaxation was further potentiated by the addition of ascorbic acid. In parallel, NO was generated from nitrite in a pH dependent manner with even larger amounts seen after addition of ascorbic acid. NO generation from nitrite correlated to the the degree of relaxation of rat aorta. These results illustrate non‐enzymatic release of NO from nitrite at physiological concentrations. This may be an important auto‐regulated physiological mechanism involved in the regulation of vascular tone during hypoxia/ischaemia.     

Nitric oxide promotes distant organ protection: evidence for an endocrine role of nitric oxide

Endothelial NOS (eNOS)-derived NO has long been considered a paracrine signaling molecule only capable of affecting nearby cells because of its short half-life in blood and relatively limited diffusion distance in tissues. To date, no studies have demonstrated that endogenously generated NO possesses a clearly defined endocrine function. Therefore, we evaluated whether enzymatic generation of NO in the heart is capable of modulating remote physiological actions and cell signaling. Mice with cardiac-specific overexpression of the human eNOS gene (CS-eNOS-Tg) were used to address this hypothesis. Cardiac-specific eNOS overexpression resulted in significant increases in nitrite, nitrate, and nitrosothiols in the heart, plasma, and liver. To examine whether the increase in hepatic NO metabolites could modulate cytoprotection, we subjected CS-eNOS-Tg mice to hepatic ischemia-reperfusion (I/R) injury. CS-eNOS-Tg mice displayed a significant reduction in hepatic I/R injury (4.2-fold reduction in the aminotransferase and a 3.5-fold reduction in aspartate aminotransferase) compared with WT littermates. These findings demonstrate that endogenously derived NO is transported in the blood, metabolized in remote organs, and mediates cytoprotection in the setting of I/R injury. This study presents clear evidence for an endocrine role of NO generated endogenously from eNOS and provides additional evidence for the profound cytoprotective actions of NO in the setting of I/R injury.     

腰椎关节手法对背根神经节伤害性疼痛大鼠疼痛行为学及一氧化氮含量的影响

目的观察腰椎关节手法对背根神经节(DRG)损伤大鼠根性疼痛的影响,探讨脊柱手法的抗炎效果及生物学机制。方法90只雄性SD大鼠随机分为空白组、假手术组、致炎+致压(复合模型)组、L5-6关节手法组、Etoricoxib组5组,各18只。各组取6只大鼠于术前1天及术后第3、5、9、15、21天行一般行为学观察和热辐射刺激缩爪反应潜伏期(PWL)的测定;另6只大鼠分别于术后第9、21天检测术侧L5 DRG中一氧化氮代谢产物亚硝酸盐含量。结果所有大鼠均未出现运动功能明显障碍。在PWL测试上,L5-6关节手法组与Etoricoxib组均比模型组明显增长(P<0.05),两组组间比较无明显差异(P>0.05)。在L5 DRG亚硝酸盐含量上,L5-6关节手法组与Etoricoxib组均比模型组明显降低(P<0.01),2组组间比较无明显差异(P>0.05)。结论模拟腰椎关节手法可以明显减轻炎性反应与机械痛敏,表现出较强的抗炎作用,其效果与口服Etoricoxib无明显区别,其镇痛效应机制可能是通过降低炎性组织中NO含量,促进炎性因子的吸收有关。     

Beetroot juice increase nitric oxide metabolites in both men and women regardless of body mass

The nitrate (NO₃^?) present in beetroot juice (BJ) has been studied for its effect on the cardiovascular system by converting to nitric oxide (NO). In the present study, we evaluated the effect of BJ on the excretion of NO metabolites and its relationship with body mass in both men and women. NO metabolites – urinary NO₃^?, nitrite (NO₂^?) and NO_x were analyzed by using a high-performance liquid chromatography system. There were significant increases in urinary NO₃^?, NO₂^? and NO_x in BJ as compared to PLA (BJ without NO₃^?). No significant difference between men and women was observed in NO metabolites after BJ at any time point. There were no significant relationships between urinary NO₃^?, NO₂^? and NO_x and body mass in BJ intervention for both men and women. In conclusion, urinary NO metabolites after BJ consumption increases in similar manner between sexes regardless of body mass.     

Vitamin E Improves Serum Paraoxonase-1 Activity and Some Metabolic Factors in Patients with Type 2 Diabetes: No Effects on Nitrite/Nitrate Levels

Objective: It is known that markers of oxidative stress and nitrite/nitrate anion (NO_x) increase and activity of antioxidative enzyme paraoxonase-1 decline in type 2 diabetes mellitus (DM). The effects of vitamin E on paraoxonase-1 activity and NO_x in patients with type 2 diabetes are not known. The purpose of this study was to examine the hypothesis that vitamin E supplementation would affect paraoxonase-1 activity, metabolic factors, and NO_x in patients with DM.

Methods: This double-blind, randomized, controlled clinical trial was conducted on 83 patients with DM aged 30–60 years. Forty-two of the subjects had taken 400 IU/day vitamin E and 41 were given placebo over 8 weeks. Fasting blood samples, anthropometric measurements, and dietary intake data were collected at the baseline and at the end of the trial.

Results: Vitamin E significantly increased serum vitamin E level, paraoxonase-1 activity, and total antioxidant status (TAS) and decreased fasting blood sugar (FBS) compared to the control group (p < 0.05). Hemoglobin A1c, serum insulin, and insulin resistance significantly decreased in the vitamin E group compared to baseline values (p < 0.05). Alterations in serum levels of malondialdehyde and NO_x were not significant in any of groups (p > 0.05).

Conclusions: Vitamin E improved serum vitamin E level, paraoxonase-1 activity, TAS, and FBS in patients with type 2 diabetes. Longitudinal studies are warranted to assess the outcome of these results in reducing complications of diabetes in patients with type 2 diabetes.     

强化碱性戊二醛杀灭微生物效果及腐蚀性试验观察

2 %强化碱性戊二醛溶液为含十七醇聚氧乙烯醚、碳酸氢钠、亚硝酸钠的戊二醛复方消毒剂 (pH8 4 7)。对其杀灭微生物效果及腐蚀性进行了试验观察。结果 ,该液对悬液中枯草杆菌黑色变种芽胞作用 1h ,杀灭率达 10 0 % ;作用 2 0min可使不锈钢片表面HBsAg抗原性破坏。其杀菌效果随戊二醛浓度减小、存在小牛血清、复方中不含亚硝酸钠而降低。其二元型原包装存放于 53～ 55℃下 14d ,戊二醛含量下降率为1 0 5% ;混合液存放室温下 2 8d者下降率达 2 9 70 %。该液对金属无或基本无腐蚀作用     

Polymorphonuclear leukocyte nitrite content and antioxidant enzymes in Parkinson's disease patients

OBJECTIVE: The present study was undertaken to evaluate the alteration in the peripheral neuronal nitric oxide synthase (NOS) activity in Parkinson's disease patients. Therefore, basal nitrite content in PMNs, platelets and in the plasma of PD and control Indian population were evaluated. MATERIALS AND METHODS: We estimated nitrite, the nitric oxide (NO) metabolite, in neutrophils (PMNs), platelets and in plasma of control and in L-dopa treated Parkinson's disease (PD) patients. We also measured the activity of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the PMNs. RESULTS: We observed a significant increase in the basal nitrite content in PMNs of PD patients without any alteration in the plasma and platelets. Thus, the change was specific to PMNs. Catalase activity was significantly less in the PMNs of PD patients, but SOD and GPx remained unaltered. CONCLUSION: Results obtained in the PD patients exhibit an increase in the NOS activity in PMNs. Thus, involvement of NO is suggested in PD.     

Benznidazole, a drug employed in the treatment of Chagas' disease, down-regulates the synthesis of nitrite and cytokines by murine stimulated macrophages.

Benznidazole (BZL) is a nitroheterocyclic drug employed in the chemotherapy of Chagas' disease, a protozoan disease caused by Trypanosoma cruzi. Because this parasite mostly replicates in macrophages, we investigated whether BZL was likely to modify the synthesis of macrophage mediators such as nitrite, tumour necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-10. Control and stimulated murine macrophages (lipopolysaccharide (LPS) and/or interferon-gamma (IFN-gamma)) were treated with BZL and measurements were carried out in culture supernatants collected 24 h later. Synthesis of nitrite, IL-6 and IL-10 was maximal upon combined stimulation with LPS + IFN-gamma, whereas lower amounts of the three mediators were detected when both stimuli were given alone. BZL treatment significantly reduced nitrite, IL-6 and IL-10 production, to undetectable levels in some cases, particularly IL-6 and IL-10. LPS was the most potent stimulus of IL-1beta and TNF-alpha production, followed by LPS + IFN-gamma and IFN-gamma in decreasing order. BZL partly inhibited TNF-alpha synthesis, but this effect was smaller than that observed for nitrite, IL-6 and IL-10. LPS-induced production of IL-1beta was also affected by BZL. Semiquantification of gene expression for inducible nitric oxide synthase (iNOS) showed that BZL completely inhibited iNOS gene induction by IFN-gamma, and resulted in respective inhibitions of 30% and 50% with LPS- and LPS + IFN-gamma-stimulated cells. BZL was not cytotoxic on macrophage cultures, as shown by the lactate dehydrogenase activity. Besides its trypanocidal activity, BZL may also alter the balance between pro- and anti-inflammatory mediators with important consequences for the course of T. cruzi infection.     

The Effect of Beetroot Ingestion on High-Intensity Interval Training: A Systematic Review and Meta-Analysis

Dietary nitrate supplementation has shown promising ergogenic effects on endurance exercise. However, at present there is no systematic analysis evaluating the effects of acute or chronic nitrate supplementation on performance measures during high-intensity interval training (HIIT) and sprint interval training (SIT). The main aim of this systematic review and meta-analysis was to evaluate the evidence for supplementation of dietary beetroot—a common source of nitrate—to improve peak and mean power output during HIIT and SIT. A systematic literature search was carried out following PRISMA guidelines and the PICOS framework within the following databases: PubMed, ProQuest, ScienceDirect, and SPORTDiscus. Search terms used were: ((nitrate OR nitrite OR beetroot) AND (HIIT or high intensity or sprint interval or SIT) AND (performance)). A total of 17 studies were included and reviewed independently. Seven studies applied an acute supplementation strategy and ten studies applied chronic supplementation. The standardised mean difference for mean power output showed an overall trivial, non-significant effect in favour of placebo (Hedges’ g = −0.05, 95% CI −0.32 to 0.21, Z = 0.39, p = 0.69). The standardised mean difference for peak power output showed a trivial, non-significant effect in favour of the beetroot juice intervention (Hedges’ g = 0.08, 95% CI −0.14 to 0.30, Z = 0.72, p = 0.47). The present meta-analysis showed trivial statistical heterogeneity in power output, but the variation in the exercise protocols, nitrate dosage, type of beetroot products, supplementation strategy, and duration among studies restricted a firm conclusion of the effect of beetroot supplementation on HIIT performance. Our findings suggest that beetroot supplementation offers no significant improvement to peak or mean power output during HIIT or SIT. Future research could further examine the ergogenic potential by optimising the beetroot supplementation strategy in terms of dosage, timing, and type of beetroot product. The potential combined effect of other ingredients in the beetroot products should not be undermined. Finally, a chronic supplementation protocol with a higher beetroot dosage (>12.9 mmol/day for 6 days) is recommended for future HIIT and SIT study.