Oxide Production In Patients Research Articles

Decreased total nitric oxide production in patients with duchenne muscular dystrophy.

Plasma nitric oxide (NO) levels in Duchenne muscular dystrophy (DMD) patients were significantly lower than those observed in both healthy controls and in patients with other neuromuscular disorders. The correlation between NO level and ejection fraction was significant (r = -0.384, p = 0.0391) in the DMD group. Disruption of NO systems may contribute to the development of muscular dystrophy and have implications for therapeutic strategies.

Decreased Total Nitric Oxide Production in Patients with Duchenne Muscular Dystrophy

Plasma nitric oxide (NO) levels in Duchenne muscular dystrophy (DMD) patients were significantly lower than those observed in both healthy controls and in patients with other neuromuscular disorders. The correlation between NO level and ejection fraction was significant (r = –0.384, p = 0.0391) in the DMD group. Disruption of NO systems may contribute to the development of muscular dystrophy and have implications for therapeutic strategies.

Intraperitoneal Nitric Oxide Production in Patients Treated by Continuous Ambulatory Peritoneal Dialysis

Background: Nitric oxide (NO) generation within the peritoneum could potentially affect peritoneal transport by increasing capillary vasodilatation, and increase peritoneal permeability during episodes of bacterial peritonitis. As peritoneal mesothelial cells have a common embryological derivation with endothelial cells, then mesothelial cells could potentially be a major source of locally produced NO. Methods: NO was measured using the Griess reaction in fresh and spent dialysate effluent (SPDE) from uninfected CAPD patients, and from those during episodes of bacterial peritonitis. Human peritoneal mesothelial cells (HPMC) were cultured and NO production determined in the presence of SPDE and the effect of a potential NO substrate, L-arginine, and NO synthase inhibitor, L-NMMA. NO production by peritoneal macrophages (MØ), obtained from SPDE and the effect of staphylococci was also determined. RNA for inducible nitric oxide synthase (iNOS) was sought using Northern blotting technique following combination stimulation with lipopolysaccharide and cytokines (IL-1β, TNF-α and γ-INF, and/or spent dialysate from patients with bacterial peritonitis). Results: Whereas fresh CAPD dialysate was nitrite-free, SPDE from the day time exchange contained 41 ± 3 µM (nitrite and nitrate), and that from the overnight dwell 91 ± 8 µM. During CAPD peritonitis, dialysate nitrite and nitrate increased from 9.3 ±0.8 to 17.5 ± 2.4 µM/l·h, for the first CAPD bag at presentation, and 15.2 ± 1.8 for the second and 16.2 ± 2.4 for the third exchange (p < 0.01 compared to non-infected control). By the second day, levels had returned to baseline, 7.3 ± 0.9 µM/l·h. HPMC produced 261 nmol nitrate and nitrite/mg cell protein, and this increased in a dose-dependent manner with the addition of spent uninfected CAPD dialysate, to 365 nmol/mg with 1:10 dilution and 655 nmol/mg with 1:2 dilution, p < 0.001. The addition of the substrate, L-arginine, resulted in a 10% increase in nitrite and nitrate production, whereas the addition of L-NMMA produced a 10% reduction. Peritoneal MØ obtained from SPDE produced similar quantities of nitrite and nitrate to peritoneal mesothelial cells, and cultures of Staphylococcus aureus resulted in a reduction in nitrite and nitrate levels, as they were used as a growth requirement. However, we could not demonstrate RNA production for iNOS by HPMC following cytokine or SPDE stimulation. Conclusions: This suggests that HPMC may be an important source of locally generated NO within the peritoneal cavity under basal conditions, but as they do not contain iNOS, the increased NO produced during episodes of acute bacterial peritonitis is more likely due to a combination of increased NO production by peritoneal endothelial cells and transmigrating macrophages.

Altered diurnal variation of nitric oxide production in patients with panic disorder.

The aim of this prospective study was to investigate the diurnal change in serum nitric oxide (NO) levels in active and remission phases of patients with panic disorder. This study included 15 patients fulfilling the criteria for panic disorder of Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition and 15 healthy controls matched for age and sex. All patients were receiving a selective serotonin reuptake inhibitor at therapeutic doses. The serum nitrite and nitrate levels of subjects were determined at 10:00 a.m. after overnight fasting and at 3:00 p.m. 2 hours after lunch. NO levels of all patients measured in the morning were significantly higher than those of controls. The patients were also divided into active and remission groups according to clinical status and Panic Agoraphobia Scale's cut-off point. There were no statistically significant differences in serum nitrite and nitrate levels of the active group between the 10:00 a.m. and 3:00 p.m. measurements. In contrast, statistically significant differences were found in the serum levels of nitrite (p<0.05) and nitrate (p<0.05) in the remission group. Notably, the afternoon nitrite and nitrate levels of the remission group were higher than those of the morning levels as seen in control subjects. Thus, diurnal variation of NO production is altered in patients with panic disorder but is resumed in the remission phase. The present study suggests that serum NO levels are a good marker for evaluation of panic disorder.

Increased nitric oxide production in patients with Behçet's disease: Is it a new activity marker?

Background: The origin of Behçet's disease (BD) is unclear. One of the prominent features of BD is vasculitis and thrombosis as a result of endothelial dysfunction. Because nitric oxide (NO) is synthesized by endothelium, we considered it as an interesting target of investigation in BD. Objective: Our purpose was to define the level of NO in the serum of patients with BD and its relation with disease activity. Methods: As an indicator for NO, serum total nitrite levels (end product of NO) were measured by Griess reaction in 52 consecutive patients with BD and compared with 32 age- and sex-matched healthy staff volunteers. Serum NO levels of active and inactive patients were compared. Results: The overall serum nitrite levels in patients with BD (40.25 ± 10.51 μmol/L) were significantly higher (P < .001) than those in healthy volunteers (25.09 ± 5.33 μmol/L). The difference in serum total nitrite levels among patients with active BD (46.74 ± 10.62 μmol/L) and inactive BD (33.24 ± 3.73 μmol/L) was significant (P < .001). Significant differences were observed in serum nitrite levels between patients in the inactive period of BD and the control group (P < .001). Conclusion: Increased NO production might be responsible for the overall inflammatory process of BD. NO seems to be related to disease activity. (J Am Acad Dermatol 2002;46:50-4.)

Increased Nitric Oxide Production in Patients with Systemic Sclerosis

Nitric oxide (NO, nitrogen monoxide) is a messenger molecule whose synthesis can be induced by proinflammatory cytokines. Increased production of NO has been reported in various inflammatory and autoimmune diseases. We studied serum nitrite and citrulline as surrogate markers for NO production in patients with systemic sclerosis (SSc) and looked for correlation with extent of disease, disease duration, age, and systemic involvement. Thirty-four patients were studied against 20 controls. The nitrite levels were significantly higher in the disease group (1588.4 ± 998.2 nmol/ml compared to 327.8 ± 137.7 nmol/ml; P < 0.001). The citrulline levels of the disease group were also significantly higher (5490.1 ± 2518.3 nmol/ml compared to 3264.5 ± 2509.7 nmol/ml in the controls; P = 0.005). There was no significant difference among limited and diffuse subgroups. There was no significant difference in patients with or without arthritis or interstitial lung disease or with other systemic involvement. On multivariate analysis there was a trend toward a rising level of nitrite with worsening lung functions (P = 0.07). Hence, there is evidence of increased NO production in patients with SSc. There is no difference between NO levels in disease subgroups or those with systemic involvement.

Markedly elevated nitrate/nitrite levels in the cerebrospinal fluid of children with progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome).

To compare the levels of brain nitric oxide production in patients with PEHO or PEHO-like syndrome and in controls with other neurologic disease. Nitric oxide metabolites, nitrates, and nitrites (NNx), were measured in the cerebrospinal fluid (CSF) of children with PEHO syndrome or PEHO-like syndrome, and in controls with other neurologic diseases. The NNx levels were markedly higher in both PEHO (mean, 48 microM; p < 0.001) and PEHO-like (22 microM; p < 0.003) patients as compared with the controls (6 microM), but did not correlate with age or with brain atrophy or CSF levels of insulin-like growth factor-1 (IGF-1). Our findings suggest that in PEHO syndrome, production of nitric oxide is markedly increased, suggesting that nitric oxide is involved in the pathologic phenomena (i.e., seizures and neurodegeneration) of the disease.

Pulmonary blood flow alters nitric oxide production in patients undergoing device closure of atrial septal defects

OBJECTIVETo determine the effect of pulmonary blood flow (Qp) on nitric oxide (NO) production in patients with increased Qp due to an atrial septal defect (ASD).BACKGROUNDAlterations in pulmonary vascular NO production have been implicated in the development of pulmonary hypertension secondary to increased Qp. In vitro, acute changes in flow or shear stress alter NO production. However, the effect of Qp on lung NO production in vivo is unclear.METHODSNineteen patients (2.4–61 years of age, median 17) with secundum ASD undergoing device closure were studied. Before, and 30 min after ASD closure, exhaled NO and plasma nitrate concentration were measured by chemiluminescence (NOA 280, Sievers, Boulder, Colorado).RESULTSBefore ASD closure, all patients had increased Qp (Qp: systemic blood flow [Qs] of 2.0 ± 0.7) and normal mean pulmonary arterial pressure (13.4 ± 3.1 mm Hg). Atrial septal defect device closure decreased Qp from 6.0 ± 2.5 to 3.6 ± 1.3 L/min/m2(p < 0.05). Mean pulmonary arterial pressure was unchanged. Associated with the decrease in Qp, both exhaled NO (−22.1%, p < 0.05) and plasma nitrate concentrations (−17.9%, p < 0.05) decreased.CONCLUSIONSThese data represent the first demonstration that acute changes in Qp alter pulmonary NO production in vivo in humans. Exhaled NO determinations may provide a noninvasive assessment of pulmonary vascular NO production in patients with congenital heart disease. Potential correlations between exhaled NO, pulmonary vascular reactivity and pulmonary hypertension warrant further study.

Increased bronchial nitric oxide production in patients with asthma measured with a novel method of different exhalation flow rates

The concentration of nitric oxide (NO) in exhaled air is increased in patients with asthma, suggesting that measuring fractional exhaled NO concentration (FENO) may be used to monitor asthmatic airway inflammation. However, increased FENO is not specific for asthma, as other inflammatory lung diseases may also increase FENO. To augment the specificity of FENO measurement, we tested a novel theoretical modelling of pulmonary NO dynamics that allows the approximation of alveolar NO concentration and bronchial NO flux separately by measuring FENO at several exhalation flow rates. We measured FENO at four exhalation flow rates in 10 steroid-naive asthmatics, 5 patients with extrinsic allergic alveolitis, and in 10 healthy controls. Both the asthmatics and the patients with alveolitis had significantly higher FENO than the healthy controls. The increased NO concentration originated from the bronchial level in the asthmatics and from the alveolar level in the patients with alveolitis. In the second part of the study we assessed the repeatability of FENO test, within-day and day-to-day (during two weeks) variation in FENO, and the effects of mouth pressure and cigarette smoking on FENO in healthy volunteers. Repeatability of 10 subsequent measurements was high (coefficient of variation (CV) 4.6% ± 0.4%), and no diurnal variation was found. The day-to-day variation during a 2-week period gave a CV of 10.6% ± 1.0%. The magnitude of mouth pressure (5-20 cmH2O in adults, 5-40 cmH2O in children) during measurement had no effect on FENO. Smoking a cigarette caused a small and transient but statistically significant increase in FENO at 1 and 5 min after smoking. In conclusion, FENO measurement is highly repeatable with low day-to-day variation among healthy subjects. Our results also suggest that the present novel method of measuring FENO at several exhalation flow rates can be used to approximate alveolar and bronchial contributions to FENO separately and thus increase the clinical value of this test.

L-Arginine Therapy Paradoxically Decreases Nitric Oxide Production in Patients with Sickle Cell Disease

L-Arginine Therapy Paradoxically Decreases Nitric Oxide Production in Patients with Sickle Cell Disease

Arginine Synthesis And Nitric Oxide Production In Patients With Pre-Eclampsia Compared To Normal Pregnant Women

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The role of nitric oxide in bradykinin-induced dilation of coronary resistance vessels in patients with hypercholesterolemia.

In hypercholesterolemic patients, acetylcholine- and substance P-mediated endothelium-dependent dilation of the coronary resistance vessels is impaired due to decreased nitric oxide production. However, it is not clear if bradykinin-induced coronary vasodilation is impaired in these patients. We investigated whether the endothelium-dependent dilation of coronary resistance vessels mediated by bradykinin is impaired in patients with hypercholesterolemia and, if so, whether this impairment is caused by a decreased production of nitric oxide. We examined the coronary vascular responses to acetylcholine and bradykinin. The vascular responses to bradykinin were also assessed after N(G)-monomethyl-L-arginine was infused to inhibit nitric oxide production. Drugs were infused into the left coronary ostium and coronary blood flow (CBF) and coronary vascular resistance were evaluated by quantitative angiography and Doppler flow velocity measurements. Twelve hypercholesterolemic patients and 11 control patients with angiographically normal coronary arteries were studied. The vasodilator responses to acetylcholine and bradykinin were reduced in hypercholesterolemic patients compared with control patients (p<0.005 and p<0.04, respectively, by two-way analysis of variance (ANOVA)). The CBF responses to acetylcholine and bradykinin were significantly correlated (r=0.56; p<0.01). Bradykinin-induced dilation was similar in hypercholesterolemic patients and control patients after inhibition of nitric oxide. These results suggest that the bradykinin-mediated endothelium-dependent dilation of coronary resistance vessels may be impaired due to depressed nitric oxide production in patients with hypercholesterolemia.

Decreased Nitric Oxide Production in Patients with Behçet’s Disease

Background: Behçet’s disease is a chronic multisystemic disorder which is characterized by a relapsing systemic inflammatory process. One of the features of Behçet’s disease is endothelial dysfunction resulting from many factors. Objective and Methods: We conducted this study to show if there is any change of plasma nitrite and nitrate levels by using the enzymatic-spectrophotometric method as an indicator for nitric oxide (NO) production, considering the disease activity in patients with Behçet’s disease. The study group consisted 21 patients and 20 healthy control subjects. We measured plasma nitrite and nitrate levels, and some acute-phase reactants including erythrocyte sedimentation rate, alpha-1-antitrypsin, alpha-2-macroglobulin and the neutrophil count. Blood samples were drawn before and after treatment of the patients. Results: Nitrite, nitrate and nitrite + nitrate levels in the active period of the disease were found to be decreased compared to the inactive period and the control group. No significant differences were observed in plasma nitrite and nitrate levels between the inactive period and the control group. Conclusion: It was concluded that decreased NO production in patients with Behçet’s disease may have critical biological activities relevant to pathologic events in the active period of the disease.

Effect of endothelin-1 on endothelium-derived vascular responsiveness in man

1. Endothelium-dependent vasodilatation via nitric oxide in response to muscarinic stimulation is decreased in chronic heart failure while basal release of nitric oxide may be increased. As production of the endothelium-derived vasoconstrictor endothelin-1 is increased in chronic heart failure, endothelin-1 may act in an autocrine manner to modulate these effects. 2. To test this, we determined whether prolonged endothelin infusion in normal subjects would reproduce the alterations in basal and stimulated nitric oxide release observed in patients with chronic heart failure. Basal nitric oxide production was determined by measurement of forearm blood flow using strain gauge venous occlusion plethysmography before and after brachial artery infusion of a nitric oxide synthase inhibitor (NG-monomethyl-L-arginine). Stimulated nitric oxide production was determined by brachial artery infusion of acetylcholine. As metabolic vasodilatation is thought to be mediated in part via nitric oxide and is decreased in chronic heart failure, forearm blood flow during peak reactive hyperaemia was also measured. Studies were then repeated during brachial artery infusion of endothelin-1 and a non-specific vasoconstrictor, noradrenaline. 3. Neither basal nor stimulated nitric oxide production was altered by endothelin-1 and noradrenaline infusion. However, absolute forearm blood flow responses to peak reactive hyperaemia were decreased during infusion of endothelin-1 in comparison to noradrenaline. These data suggest that increased endothelin-1 may not contribute greatly to altered basal and stimulated nitric oxide production in patients with chronic heart failure but may contribute to impaired metabolic vasodilatation, by mechanisms presumably unrelated to altered nitric oxide production.

Low Nitric Oxide Production in Patients with Chronic Renal Failure

Background: Rats with chronic renal failure have a low nitric oxide (NO) production and a diminished NO excretion. The supplementation of L-arginine has an inhibitory effect on the progression of renal insufficiency. Methods: The present study was designed to determine whether chronic renal failure patients have a low NO production. Plasma and urine nitrate (NO₃) and nitrite (NO₂), stable metabolites of NO, were measured in 83 consecutive patients with chronic renal failure. The 83 chronic renal failure patients were divided into three groups: group 1, mild renal failure (creatinine clearance >60 ml/min/1.73 m²); group 2, moderate renal failure (creatinine clearance >30 <60 ml/min/1.73 m²), and group 3, severe renal failure (creatinine clearance <30 ml/min/1.73 m²). Thirty-three healthy volunteers served as controls. Results: The daily urinary NO excretion was significantly lower in patients with moderate and severe renal failure as compared with those with mild renal failure and normal controls. The lowest values were found in the severe renal failure group. When the 24-hour urinary NO excretion or NO per milligram creatinine and the NO clearance were correlated with the renal function in all patients as a group, these parameters were directly correlated with the creatinine clearance and inversely correlated with the serum creatinine level. The plasma NO concentration was not different between the three chronic renal failure groups, but higher than in the controls. Plasma NO in renal failure patients was not correlated with the creatinine clearance or serum creatinine levels. Conclusions: Chronic renal failure is a state of NO deficiency. Treatment strategies to increase NO production (L-arginine supplementation or other NO compounds) may prove to be useful in maintaining the renal function and slow the progression of renal disease.

Increased Nitric Oxide Production in Patients with Hypotension during Hemodialysis

To determine the involvement of nitric oxide production in hemodialysis-induced hypotension. Examination of nitric oxide synthesis, cyclic guanosine 3'5'-monophosphate (cGMP) levels, and endothelin-1 levels in plasma before and after hemodialysis. Veterans Affairs medical center. 13 patients with end-stage renal failure who were receiving hemodialysis: Six patients had hypotensive episodes during dialysis and 7 did not. Patients received heparin at a bolus dose of 2000 U at the initiation of dialysis followed by 1000 U/h during 4-hour hemodialysis sessions. Nitric oxide production markedly increased during hemodialysis-induced hypotensive episodes; this increase was not seen in patients who did not have a hypotensive episode. In both groups, the plasma cGMP and endothelin-1 levels decreased after hemodialysis. According to multiple regression analysis, standard coefficients of nitric oxide production, plasma cGMP levels, and endothelin-1 levels with mean blood pressure after hemodialysis were -0.743, -0.07, and 0.31, respectively. Nitric oxide production increased in patients who had a hypotensive episode during hemodialysis but did not increase in those who did not have a hypotensive episode.

Decreased antioxidant status and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction.

To determine antioxidant vitamin concentrations, lipid peroxidation, and an index of nitric oxide production in patients in the intensive care unit (ICU) with septic shock and relate the findings to the presence of secondary organ failure. A prospective, observational study. A nine-bed ICU in a University teaching hospital. Sixteen consecutive patients with septic shock, defined as: a) clinical evidence of acute infection; b) hypo- or hyperthermia (< 35.6 degrees C or > 38.3 degrees C); c) tachypnea (> 20 breaths/min or being mechanically ventilated); d) tachycardia (> 90 beats/min); e) shock (systolic pressure < 90 mm Hg) or receiving inotropes. Fourteen patients also had secondary organ dysfunction. None. Antioxidant vitamin concentrations were significantly lower in the patients than the reference range obtained from a comparable group of healthy controls. The mean plasma retinol (vitamin A) concentration was 26.5 +/- 19.3 micrograms/dL compared with 73.5 +/- 18.3 micrograms/dL in healthy subjects (p < .01). Additionally, 13 (81%) patients had retinol values below the lower limit of our reference range (< 37.0 micrograms/dL). Tocopherol (vitamin E) plasma concentrations were below the reference range in all patients (< 9.0 mg/L), with a mean value of 3.6 +/- 2.0 mg/L compared with 11.5 +/- 1.3 mg/L in healthy subjects (p < .001). Plasma beta carotene and lycopene concentrations were undetectable (< 15 micrograms/L) in eight (50%) patients, and below our reference range (< 101 micrograms/L and < 154 micrograms/L, respectively) in the remaining patients. In the five patients with three or more dysfunctional secondary organs, plasma thiobarbituric acid-reactive substances were significantly increased (p < .05), suggesting increased lipid peroxidation. Concentrations of thiobarbituric acid-reactive substances correlated negatively with both plasma retinol and plasma tocopherol (r2 = .42, p < .01 and r2 = .48, p < .005, respectively). In the five patients from whom we were able to collect urine, nitrite excretion was increased approximately 400-fold (p < .001). These data indicate decreased antioxidant status in the face of enhanced free radical activity, and suggest potential therapeutic strategies involving antioxidant repletion.

Nitric oxide production in patients with chronic liver diseases

Nitric oxide production in patients with chronic liver diseases