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High-nitrate salad increased plasma nitrates/nitrites and brachial artery flow-mediated dilation in postmenopausal women: A pilot study.
Mayra, ST, Johnston, CS, Sweazea, KL
Nutrition research (New York, N.Y.). 2019;:99-104
Abstract
Cardiovascular disease risk is elevated in postmenopausal women relative to men of the same age or to younger, premenopausal women. This elevated risk is closely linked to the loss of estrogen, which is a potent stimulator of the vasodilator nitric oxide. While studies have largely supported dietary nitrate supplementation (typically concentrated beetroot juice) to augment plasma nitric oxide, these studies focused mainly on improving vascular fitness of athletes or patient populations. The purpose of this controlled crossover trial was to assess the feasibility of consuming a high-nitrate, leafy green salad twice daily for 10 consecutive days versus a low-nitrate, canned vegetable control (beans, corn, or peas) on plasma nitrate/nitrite concentration and measures of cardiovascular health in postmenopausal women. We hypothesized that plasma nitrate/nitrite concentration and flow-mediated dilation would improve following the leafy green salad treatment. Ten women (52.6 ± 4.9 y; 26.4 ± 6.4 kg/m2) completed the two 10-day treatment periods separated by 2-3 weeks washout. The mean fasting plasma nitrate/nitrite concentration was significantly increased following the high-nitrate salad treatment compared to the control (+156% and+ 16% respectively; P = .002, effect size = 0.661). Flow-mediated dilation responded favorably to the high nitrate salad in comparison to the canned vegetable condition (+17% versus -8% respectively; P = .047, effect size = 0.407); however, there were no treatment effects on peripheral or derived central-aortic blood pressure. These data suggest that daily ingestion of nitrate-rich, leafy green salads may prove a useful strategy for improving cardiovascular health in postmenopausal women.
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Hydroxyurea therapy modulates sickle cell anemia red blood cell physiology: Impact on RBC deformability, oxidative stress, nitrite levels and nitric oxide synthase signalling pathway.
Nader, E, Grau, M, Fort, R, Collins, B, Cannas, G, Gauthier, A, Walpurgis, K, Martin, C, Bloch, W, Poutrel, S, et al
Nitric oxide : biology and chemistry. 2018;:28-35
Abstract
Hydroxyurea (HU) has been suggested to act as a nitric oxide (NO) donor in sickle cell anemia (SCA). However, little is known about the HU NO-related effects on red blood cell (RBC) physiology and NO signalling pathway. Thirty-four patients with SCA (22 under HU treatment (HU+) and 12 without (HU-)) and 17 healthy subjects (AA) were included. RBC nitrite content, deformability and reactive oxygen species (ROS) levels were measured. RBC NO-synthase (RBC-NOS) signalling pathway was assessed by the measurement of RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation. We also investigated the in vitro effects of Sodium Nitroprusside (SNP), a NO donor, on the same parameters in SCA RBC. RBC nitrite content was higher in HU+ than in HU- and AA. RBC deformability was decreased in SCA patients compared to AA but the decrease was more pronounced in HU-. RBC ROS level was increased in SCA compared to AA but the level was higher in HU- than in HU+. RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation were decreased in HU+ compared to HU- and AA. SCA RBC treated with SNP showed increased deformability, reduced ROS content and a decrease in AKT and RBC-NOS phosphorylation. Our study suggests that HU, through its effects on foetal hemoglobin and possibly on NO delivery, would modulate RBC NO signalling pathway, RBC rheology and oxidative stress.
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Diabetes status differentiates endothelial function and plasma nitrite response to exercise stress in peripheral arterial disease following supervised training.
Allen, JD, Stabler, T, Kenjale, AA, Ham, KL, Robbins, JL, Duscha, BD, Kraus, WE, Annex, BH
Journal of diabetes and its complications. 2014;(2):219-25
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Abstract
AIMS: To determine if type 2 diabetes mellitus (T2D) differentiates endothelial function and plasma nitrite response (a marker of nitric oxide bioavailability) during exercise in peripheral arterial disease (PAD) subjects prior to and following 3 months supervised exercise training (SET). METHODS In subjects with T2D+PAD (n = 13) and PAD-only (n = 14), endothelial function was measured using brachial artery flow-mediated dilation. On a separate day, venous blood draws were performed at rest and 10 min following a symptom-limited graded treadmill test (SL-GXT). Plasma samples were snap-frozen for analysis of nitrite by reductive chemiluminescence. All testing was repeated following 3 months of SET. RESULTS Prior to training both groups demonstrated endothelial dysfunction, which was correlated with a net decrease in plasma nitrite following a SL-GXT (p ≤ 0.05). Following SET, the PAD-only group demonstrated an improvement in endothelial function (p ≤ 0.05) and COT (p ≤ 0.05), which was related to a net increase in plasma nitrite following the SL-GXT (both p ≤ 0.05). The T2D+PAD group had none of these increases. CONCLUSIONS T2D in the presence of PAD attenuated improvements in endothelial function, net plasma nitrite, and COT following SET. This suggests that T2D maybe associated with an inability to endogenously increase vascular NO bioavailability to SET.
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Low nitric oxide bioavailability is associated with better responses to sildenafil in patients with erectile dysfunction.
Muniz, JJ, Lacchini, R, Sertório, JT, Jordão, AA, Nobre, YT, Tucci, S, Martins, AC, Tanus-Santos, JE
Naunyn-Schmiedeberg's archives of pharmacology. 2013;(9):805-11
Abstract
Erectile dysfunction (ED) is a multifactorial disease associated with vascular dysfunction, low nitric oxide (NO) bioavailability, and oxidative stress. However, it is not known whether low NO bioavailability and oxidative stress affect the responsiveness of ED patients to sildenafil. We tested this hypothesis by studying 28 healthy subjects (control group), 26 patients with ED without comorbidities (ED group), and 18 patients with ED and diabetes mellitus (ED/DM group). The International Index for Erectile Function (IIEF) questionnaire was used to assess the erectile function of all participants, and their responsiveness to sildenafil was assessed as the percentage of change in the five-item version of IIEF score before and after sildenafil treatment. Levels of whole blood nitrite, antioxidants markers (ferric reducing ability of plasma (FRAP) and reduced glutathione), and oxidative stress markers (thiobarbituric acid reactive substance and protein carbonyl) were determined. We found a negative correlation between whole blood nitrite levels and the responses to sildenafil in both ED groups (P<0.05). FRAP correlated negatively with the responses to sildenafil in the ED/DM group (P<0.05). No other significant associations were found. Our findings show evidence that low NO bioavailability is associated with better responses to sildenafil in patients with ED (with or without DM).
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The effect of specific immunotherapy on exhaled breath condensate nitrite levels.
Inci, D, Altintaş, DU, Kendirli, SG, Yilmaz, M, Karakoç, GB
Allergy. 2006;(7):899-900
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Broad-band ultraviolet B phototherapy is associated with elevated serum thiobarbituric acid reactive substance and nitrite-nitrate levels in psoriatic patients.
Kilinc Karaarslan, I, Girgin Sagin, F, Ertam, I, Alper, S, Ozturk, G, Yildirim Sozmen, E
Journal of the European Academy of Dermatology and Venereology : JEADV. 2006;(10):1226-31
Abstract
BACKGROUND Although the local anti-inflammatory, immunosuppressive and oxidative activity of UVB is known, the systemic effect of UVB phototherapy in dermatological patients has not been investigated. OBJECTIVE We aimed to investigate the lipid peroxidation status (as represented by thiobarbituric acid reactive substance, TBARS) and nitrite-nitrate levels in psoriatic patients under broad-band ultraviolet B (BB-UVB) phototherapy in order to determine the systemic effects of UVB. SUBJECTS AND METHODS Thirty-two psoriatic patients and 20 healthy controls were included. Blood samples were obtained at the beginning, after 6-10 exposures to BB UVB phototherapy (mean 5 weeks) and at the end of the therapy period (mean 21 weeks). Serum TBARS and nitrite-nitrate levels were evaluated. RESULTS There was no statistically significant difference in serum TBARS and nitrite-nitrate levels between psoriatic patients (basal) and healthy volunteers. There was no statistically significant correlation between disease duration, disease severity, or the total cumulative dose of UVB and serum levels of TBARS and nitrite-nitrate in psoriatic patients. Total nitrite levels in samples obtained during and at the end of therapy were significantly higher than basal levels (P=0.033 and P=0.005, respectively). TBARS levels in samples obtained during and at the end of therapy were significantly higher than basal levels (P=0 and P=0.026, respectively). There was a negative correlation (r=-0.576, P=0.039) between the total nitrite and TBARS levels in psoriatic patients at the end of therapy. CONCLUSION Our study showed that chronic exposure to UV irradiation may lead to a systemic effect on lipid peroxidation and NO levels, which are shown by a significant elevation in TBARS and nitrite-nitrate levels in serum.
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eNOS gene T-786C polymorphism modulates atorvastatin-induced increase in blood nitrite.
Nagassaki, S, Sertório, JT, Metzger, IF, Bem, AF, Rocha, JB, Tanus-Santos, JE
Free radical biology & medicine. 2006;(7):1044-9
Abstract
Statins inhibit cholesterol synthesis and produce pleiotropic, cholesterol-independent effects including endothelial NO synthase (eNOS) stimulation and increased expression. However, a functional polymorphism in the promoter of the eNOS gene (T-786C) reduces its activity and could modulate the response to statins. Here, we examined whether this polymorphism modulates the effects of atorvastatin on the plasma levels of markers of NO formation and oxidative stress. We genotyped 200 healthy subjects for this polymorphism, and 15 subjects with the TT genotype and 15 with the CC genotype were selected to receive placebo or atorvastatin 10 mg/day po for 14 days. To assess NO bioavailability, the plasma concentrations of nitrate, nitrite, and cGMP and the whole blood nitrite concentrations were determined after placebo or atorvastatin using an ozone-based chemiluminescence assay and an enzyme immunoassay. Thiobarbituric acid-reactive species (TBA-RS) were measured in the plasma to assess oxidative stress. Atorvastatin decreased cholesterol concentrations independent of genotype. Whereas atorvastatin produced no significant changes in plasma nitrite, nitrate, or cGMP concentrations in both genotype groups, atorvastatin increased whole blood nitrite concentrations and decreased plasma TBA-RS concentrations in the CC (but not in the TT) genotype group. These findings suggest that the T-786C polymorphism modulates the effects of atorvastatin on NO bioavailability and oxidative stress.