-
1.
Sex differences in the nitrate-nitrite-NO• pathway: Role of oral nitrate-reducing bacteria.
Kapil, V, Rathod, KS, Khambata, RS, Bahra, M, Velmurugan, S, Purba, A, S Watson, D, Barnes, MR, Wade, WG, Ahluwalia, A
Free radical biology & medicine. 2018;:113-121
Abstract
Oral reduction of nitrate to nitrite is dependent on the oral microbiome and is the first step of an alternative mammalian pathway to produce nitric oxide in humans. Preliminary evidence suggests important sex differences in this pathway. We prospectively investigated sex-differences following inorganic nitrate supplementation on nitrate/nitrite levels and vascular function, and separately examined sex differences in oral nitrate reduction, and oral microbiota by 16S rRNA profiling. At baseline, females exhibit higher nitrite levels in all biological matrices despite similar nitrate levels to males. Following inorganic nitrate supplementation, plasma nitrite was increased to a significantly greater extent in females than in males and pulse wave velocity was only reduced in females. Females exhibited higher oral bacterial nitrate-reducing activity at baseline and after nitrate supplementation. Despite these differences, there were no differences in the composition of either the total salivary microbiota or those oral taxa with nitrate reductase genes. Our results demonstrate that females have augmented oral nitrate reduction that contributes to higher nitrite levels at baseline and also after inorganic nitrate supplementation, however this was not associated with differences in microbial composition (clinicaltrials.gov: NCT01583803).
-
2.
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.
-
3.
Effects of low-dose fluticasone propionate/salmeterol combination therapy on exhaled nitric oxide and nitrite/nitrate in breath condensates from patients with mild persistent asthma.
Pasha, MA, Smith, TC, Feustel, PJ, Jourd'heuil, D
The Journal of asthma : official journal of the Association for the Care of Asthma. 2013;(1):64-70
Abstract
OBJECTIVE The long-acting β2-agonist salmeterol in combination with the corticosteroid fluticasone propionate is used in clinical practice for the treatment of mild persistent asthma. Although the effect of fluticasone propionate alone in asthmatic patients is well documented, the effect of fluticasone propionate/salmeterol (FSC) combination therapy on airway inflammation and airway hyperresponsiveness (AHR) is not well characterized. Thus, we evaluated AHR, exhaled nitric oxide (FE(NO)), and nitrite and nitrate in exhaled breath condensates (EBCs) from mild persistent asthmatic patients treated with a low-dose FSC (100/50). METHODS In this open label study, 18 mild persistent, steroid-naïve asthmatics (age, 22-62 years, forced expiratory volume in 1 s (FEV(1)) > 70% predicted, provocative dose resulting in 20% reduction (PD(20)) < 10 mg/mL) were treated with FSC 100/50 for 4 weeks. PD(20) to methacholine, FEV(1), FE(NO), and EBC nitrite and nitrate was measured before and after treatment. RESULTS After 4 weeks of therapy with FSC 100/50, FE(NO) decreased from 74 ppb (SD = 37) to 34 ppb (SD = 15) (p < .001). FEV(1) (% predicted) increased from 89.4 (SD = 10.7) to 93.3 (SD = 9.5) (p < .01). The PD(20) for methacholine increased from 3.0 (±3.2) to 10.3 (±8.4) mg/mL (p < .01) in 3 of 18 patients reaching the maximum allowable dose (25 mg/mL). FE(NO) correlated with the log of the methacholine dose. There was no statistically significant change in EBC nitrite and nitrate before and after treatment. CONCLUSIONS Treatment of mild persistent, steroid-naïve asthmatics with low-dose combination therapy is effective in rapidly reducing airway inflammation and AHR. Our results suggest different metabolic origins for nitrite, nitrate, and FE(NO) in this group of patients.
-
4.
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
-
-
Free full text
-
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.
-
5.
Proanthocyanidins in buckwheat flour can reduce salivary nitrite to nitric oxide in the stomach.
Takahama, U, Tanaka, M, Hirota, S
Plant foods for human nutrition (Dordrecht, Netherlands). 2010;(1):1-7
Abstract
Buckwheat flour, which is used for various dishes in the world, is a good source of proanthocyanidins. Proanthocyanidins in the buckwheat flour reduced nitrous acid producing nitric oxide (NO) when the flour was suspended in acidified saliva or in acidic buffer solution in the presence of nitrite. The ingestion of dough prepared from buckwheat flour increased the concentration of NO in the air expelled from the stomach, suggesting that the proanthocyanidins also reduced nitrite to NO in the stomach. During the production of NO by the buckwheat flour/nitrous acid systems, oxidation, nitration, and nitrosation of proanthocyanidins proceeded. The increase in the concentration of NO could improve the activity of stomach helping the digestion of ingested foods and the nitration and nitrosation of the proanthocyanidins could contribute to the scavenging of reactive nitrogen oxide species generated from NO and nitrous acid.
-
6.
Acute effects of hydrocortisone on plasma nitrate/nitrite activity and forearm vasodilator responsiveness in normal human subjects.
Williamson, PM, Kohlhagen, JL, Mangos, GJ, Whitworth, JA, Kelly, JJ
Clinical and experimental pharmacology & physiology. 2005;(3):162-6
Abstract
1. The aim of the present study was to examine the acute effects of cortisol infusion on plasma nitrate/nitrite (NO) activity and forearm vascular responsiveness to acetylcholine. 2. We performed two randomized, placebo-controlled, cross-over studies. Study A examined the effects of intravenous hydrocortisone (200 mg over a 3 h period) on blood pressure (BP) and plasma NO activity in six healthy male volunteers. Study B examined the effects of intra-arterial hydrocortisone on cholinergic vasodilator responsiveness in six healthy male volunteers. Vasodilator responsiveness was measured by bilateral strain gauge plethysmography. 3. In study A, there was no significant change in BP during the hydrocortisone infusion. Comparing values obtained following 180 min infusion of hydrocortisone and control, there were significant increases in plasma cortisol (3441 +/- 342 vs 209 +/- 29 nmol/L, respectively; P < 0.001) and glucose (5.7 +/- 0.2 vs 4.6 +/- 0.2 mmol/L, respectively; P < 0.05) and a reduction in plasma renin concentration (PRC) (8.1 +/- 1.2 vs 11.0 +/- 1.8 pg/mL, respectively; P < 0.05) following hydrocortisone infusion. However, there were no significant changes in either plasma NO or in the endogenous NO synthase inhibitors asymmetrical and symmetrical dimethylarginine. 4. In study B, there was no significant change in BP or in cholinergic vasodilator responsiveness during the hydrocortisone infusion. 5. Short-term cortisol infusions do not alter biochemical or physiological markers of NO activity. If cortisol-induced hypertension is mediated by suppression of NO activity in humans, it seems likely that these changes take more than 3 h to become detectable.
-
7.
Aconiti tuber increases plasma nitrite and nitrate levels in humans.
Yamada, K, Suzuki, E, Nakaki, T, Watanabe, S, Kanba, S
Journal of ethnopharmacology. 2005;(1-2):165-9
Abstract
Some herbal medicines, including Aconiti tuber (Aconitum carmichaeli Debeaux, Ranunculaceae), have been recognized as being effective for the treatment of a "peripheral uncomfortable feeling of cold (hie)". We hypothesized that these compounds affect peripheral vascular function via the nitric oxide (NO) system, which leads to recovery from "hie". To answer this question, we investigated Aconiti tuber-induced changes in plasma levels of nitrite (p-NO2-) and nitrate (p-NO3-), final nitric oxide-oxidation products measurable in vivo. After written informed consent was obtained, patients suffering from "hie" were treated with several kinds of kampo (Japanese traditional herbal medicine), selected on the basis of traditional theory. Twenty-four patients took kampo formulas, some included Aconiti tuber (n=11; A-group) and others did not (n=13; C-group), for 4 weeks. p-NO2- and p-NO3- levels were measured before the start and after 4 weeks of treatment. In the A-group, the p-NO2- plus p-NO3- (p-NOx) level was significantly increased at 4 weeks (p=0.04), while that of the C-group was not. There was a statistically significant increase in the p-NOx level of the A-group as compared to the C-group (d.f.=1,22, F=9.38, p=0.006). The results suggest that Aconiti tuber may increase NO production in humans.
-
8.
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.
-
9.
Arginine vasopressin and serum nitrite/nitrate concentrations in advanced vasodilatory shock.
Dünser, MW, Werner, ER, Wenzel, V, Ulmer, H, Friesenecker, BE, Hasibeder, WR, Mayr, AJ
Acta anaesthesiologica Scandinavica. 2004;(7):814-9
Abstract
BACKGROUND Arginine-vasopressin (AVP) can successfully stabilize hemodynamics in patients with advanced vasodilatory shock. It has been suggested that inhibition of cytokine-induced nitric oxide production may be an important mechanism underlying AVP-induced vasoconstriction. Therefore, serum concentrations of nitrite/nitrate (NOx), the stable metabolite of nitric oxide, were measured in patients suffering from advanced vasodilatory shock treated with either AVP in combination with norepinephrine (NE) or NE alone. METHODS This trial was a separate study arm of a previously published prospective, randomized, controlled study on the effects of AVP in advanced vasodilatory shock. Thirty-eight patients were prospectively randomized to receive a combined infusion of AVP (4 U h(-1)) and NE, or NE infusion alone. Serum NOx concentrations were measured at baseline, 24, and 48 h after randomization. The increase in mean arterial pressure during the first hour after study enrollment was documented in all patients. RESULTS No difference in NOx concentrations was found between groups throughout the study period. AVP patients demonstrated a significantly greater increase in mean arterial pressure than NE patients (22 +/- 10 vs. 5 +/- 9 mmHg; P < 0.001). The magnitude of pressure response to AVP was not correlated with NOx concentrations before start of AVP infusion (Pearson's correlation coefficient, -.009; P = 0.971). CONCLUSION Cardiovascular effects of AVP infusion in advanced vasodilatory shock are not mediated by a clinically relevant reduction in serum NOx concentrations. Therefore, hemodynamic improvement of patients in advanced vasodilatory shock during continuous infusion of AVP has to be attributed to other mechanisms than inhibition of nitric oxide synthase. In addition, the magnitude of pressure response to AVP is not correlated with baseline concentrations of NOx.
-
10.
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
-
-
Free full text
-
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.