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Dietary nitrate supplementation: effects on plasma nitrite and pulmonary O2 uptake dynamics during exercise in hypoxia and normoxia.
Kelly, J, Vanhatalo, A, Bailey, SJ, Wylie, LJ, Tucker, C, List, S, Winyard, PG, Jones, AM
American journal of physiology. Regulatory, integrative and comparative physiology. 2014;(7):R920-30
Abstract
We investigated the effects of dietary nitrate (NO3 (-)) supplementation on the concentration of plasma nitrite ([NO2 (-)]), oxygen uptake (V̇o2) kinetics, and exercise tolerance in normoxia (N) and hypoxia (H). In a double-blind, crossover study, 12 healthy subjects completed cycle exercise tests, twice in N (20.9% O2) and twice in H (13.1% O2). Subjects ingested either 140 ml/day of NO3 (-)-rich beetroot juice (8.4 mmol NO3; BR) or NO3 (-)-depleted beetroot juice (PL) for 3 days prior to moderate-intensity and severe-intensity exercise tests in H and N. Preexercise plasma [NO2 (-)] was significantly elevated in H-BR and N-BR compared with H-PL (P < 0.01) and N-PL (P < 0.01). The rate of decline in plasma [NO2 (-)] was greater during severe-intensity exercise in H-BR [-30 ± 22 nM/min, 95% confidence interval (CI); -44, -16] compared with H-PL (-7 ± 10 nM/min, 95% CI; -13, -1; P < 0.01) and in N-BR (-26 ± 19 nM/min, 95% CI; -38, -14) compared with N-PL (-1 ± 6 nM/min, 95% CI; -5, 2; P < 0.01). During moderate-intensity exercise, steady-state pulmonary V̇o2 was lower in H-BR (1.91 ± 0.28 l/min, 95% CI; 1.77, 2.13) compared with H-PL (2.05 ± 0.25 l/min, 95% CI; 1.93, 2.26; P = 0.02), and V̇o2 kinetics was faster in H-BR (τ: 24 ± 13 s, 95% CI; 15, 32) compared with H-PL (31 ± 11 s, 95% CI; 23, 38; P = 0.04). NO3 (-) supplementation had no significant effect on V̇o2 kinetics during severe-intensity exercise in hypoxia, or during moderate-intensity or severe-intensity exercise in normoxia. Tolerance to severe-intensity exercise was improved by NO3 (-) in hypoxia (H-PL: 197 ± 28; 95% CI; 173, 220 vs. H-BR: 214 ± 43 s, 95% CI; 177, 249; P = 0.04) but not normoxia. The metabolism of NO2 (-) during exercise is altered by NO3 (-) supplementation, exercise, and to a lesser extent, hypoxia. In hypoxia, NO3 (-) supplementation enhances V̇o2 kinetics during moderate-intensity exercise and improves severe-intensity exercise tolerance. These findings may have important implications for individuals exercising at altitude.
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Inhaled nitric oxide therapy increases blood nitrite, nitrate, and s-nitrosohemoglobin concentrations in infants with pulmonary hypertension.
Ibrahim, YI, Ninnis, JR, Hopper, AO, Deming, DD, Zhang, AX, Herring, JL, Sowers, LC, McMahon, TJ, Power, GG, Blood, AB
The Journal of pediatrics. 2012;(2):245-51
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Abstract
OBJECTIVE To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension. STUDY DESIGN In this single center study, 5 sequential blood samples were collected from infants with pulmonary hypertension before, during, and after therapy with iNO (n = 17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n = 16) and from healthy adults for comparison (n = 12). RESULTS After beginning iNO (20 ppm) whole blood nitrite levels increased approximately two-fold within 2 hours (P<.01). Whole blood nitrate levels increased to 4-fold higher than baseline during treatment with 20 ppm iNO (P<.01). S-nitrosohemoglobin increased measurably after beginning iNO (P<.01), whereas iron nitrosyl hemoglobin and total hemoglobin-bound NO-species compounds did not change. CONCLUSION Treatment of pulmonary hypertensive infants with iNO results in increases in levels of nitrite, nitrate, and S-nitrosohemoglobin in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart, and other organs.
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Estrogen therapy increases plasma concentrations of nitric oxide metabolites in postmenopausal women but increases flow-mediated vasodilation only in younger women.
López-Jaramillo, P, Díaz, LA, Pardo, A, Parra, G, Jaimes, H, Chaudhuri, G
Fertility and sterility. 2004;(6):1550-5
Abstract
OBJECTIVE To evaluate the effect of estrogen therapy (ET) on endothelial nitric oxide (NO) production and in flow-mediated vasodilation (FMV). DESIGN Randomized, crossover, double-blind, placebo-controlled study. SETTING Healthy postmenopausal women in an academic research environment. PATIENT(S): Forty postmenopausal women between 45 and 72 years of age. INTERVENTION(S): Women received ET or placebo during two periods of 12 weeks that were separated by 2 weeks of washout. MAIN OUTCOME MEASURE(S): Flow-mediated vasodilation, nitrite and nitrate, lipid profile, creatinine, and glucose were measured at weeks 12 and 24. Student's t or Wilcoxon tests were used for comparative analyses, and kappa test and limit analysis determined variability. RESULT(S): After placebo treatment, nitrate and nitrite mean concentration was 8.28 +/- 1.17 mmol/L; it increased to 62.6 +/- 12.82 mmol/L after ET. Percentage FMV was 18.8 +/- 2.58 after the placebo period and did not change after ET (20.1 +/- 1.92) in the whole sample, but in the subgroup (n = 15) of younger women (45-50 years of age), percentage FMV increased from 13.6 +/- 3.6 after the placebo period to 22.2 +/- 3.5 after ET. CONCLUSION(S): An increase in plasma concentrations of nitrite and nitrate after ET was observed in all the women studied, but the improvement in FMV was observed only in the younger ones. These age-related differences in FMV in response to ET must be further investigated.
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Decreasing resistance in the maternal uterine and peripheral arterial system is apparently unrelated to plasma and urinary levels of nitrite/nitrate and cyclic-guanosinmonophosohate during the course of normal pregnancies.
Schiessl, B, Strasburger, CJ, Bidlingmaier, M, Spannagl, M, Ugele, B, Kainer, F
Journal of perinatal medicine. 2003;(4):281-6
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Abstract
AIMS: The aim of the presented study was to clarify the relationship between the pulsatility index of the uterine arteries and the maternal cubital artery and peripheral concentrations of the metabolites of nitric oxide (NO) and its second messenger cyclic guanosinmonophophate (cGMP) during the normal course of pregnancy and postpartum. METHODS 49 uncomplicated pregnancies were investigated every 4-6 weeks until delivery, 29 of them were additionally investigated postpartum. Paralleling each Doppler sonographic investigation maternal blood and urine samples were taken. The measurements of nitrite/nitrate and cGMP were performed with a colorimetric and radio immuno assay. We demonstrate a significant decrease of the PI of the uterine arteries and of the cubital artery with inverse correlation to advancing gestational age. RESULTS The concentrations of nitrite/nitrate and cGMP remain stable during gestation and do not correlate to the PI of the uterine and cubital artery. Postpartum a re-increase in the uterine and peripheral resistance can be shown. The concentrations of urinary cGMP and nitrite/nitrate as well as plasma cGMP remain unchanged, whereas plasma nitrite/nitrate decreases postpartum. CONCLUSIONS The status of NO biosyntheses in normal pregnancy remains controversial. We hypothesize further systemically acting mediators which contribute to the decreasing vascular resistance.