| 1. |
- Flockhart, Mikael, et al.
(author)
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Glucosinolate-rich broccoli sprouts protect against oxidative stress and improve adaptations to intense exercise training.
- 2023
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In: Redox Biology. - : Elsevier. - 2213-2317. ; 67
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Journal article (peer-reviewed)abstract
- Oxidative stress plays a vital role for the adaptive responses to physical training. However, excessive oxidative stress can precipitate cellular damage, necessitating protective mechanisms to mitigate this effect. Glucosinolates, found predominantly in cruciferous vegetables, can be converted into isothiocyanates, known for their antioxidative properties. These compounds activate crucial antioxidant defence pathways and support mitochondrial function and protein integrity under oxidative stress, in both Nrf2-dependent and independent manners. We here administered glucosinolate-rich broccoli sprouts (GRS), in a randomized double-blinded cross-over fashion to 9 healthy subjects in combination with daily intense exercise training for 7 days. We found that exercise in combination with GRS significantly decreased the levels of carbonylated proteins in skeletal muscle and the release of myeloperoxidase into blood. Moreover, it lowered lactate accumulation during submaximal exercise, and attenuated the severe nocturnal hypoglycaemic episodes seen during the placebo condition. Furthermore, GRS in combination with exercise improved physical performance, which was unchanged in the placebo condition.
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| 2. |
- Montenegro, Marcelo F, et al.
(author)
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Blood Pressure-Lowering Effect of Orally Ingested Nitrite Is Abolished by a Proton Pump Inhibitor.
- 2017
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In: Hypertension. - 0194-911X .- 1524-4563. ; 69:1, s. 23-31
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Journal article (peer-reviewed)abstract
- Inorganic nitrate and nitrite from dietary and endogenous sources are metabolized to NO and other bioactive nitrogen oxides that affect blood pressure. The mechanisms for nitrite bioactivation are unclear, but recent studies in rodents suggest that gastric acidity may influence the systemic effects of this anion. In a randomized, double-blind, placebo-controlled crossover study, we tested the effects of a proton pump inhibitor on the acute cardiovascular effects of nitrite. Fifteen healthy nonsmoking, normotensive subjects, aged 19 to 39 years, were pretreated with placebo or esomeprazole (3×40 mg) before ingesting sodium nitrite (0.3 mg kg(-1)), followed by blood pressure monitoring. Nitrite reduced systolic blood pressure by a maximum of 6±1.3 mm Hg when taken after placebo, whereas pretreatment with esomeprazole blunted this effect. Peak plasma nitrite, nitrate, and nitroso species levels after nitrite ingestion were similar in both interventions. In 8 healthy volunteers, we then infused increasing doses of sodium nitrite (1, 10, and 30 nmol kg(-1) min(-1)) intravenously. Interestingly, although plasma nitrite peaked at similar levels as with orally ingested nitrite (≈1.8 µmol/L), no changes in blood pressure were observed. In rodents, esomeprazole did not affect the blood pressure response to the NO donor, DEA NONOate, or vascular relaxation to nitroprusside and acetylcholine, demonstrating an intact downstream NO-signaling pathway. We conclude that the acute blood pressure-lowering effect of nitrite requires an acidic gastric environment. Future studies will reveal if the cardiovascular complications associated with the use of proton pump inhibitors are linked to interference with the nitrate-nitrite-NO pathway.
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| 3. |
- Schiffer, Tomas A, et al.
(author)
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Control of Human Energy Expenditure by Cytochrome C Oxidase Subunit IV-2.
- 2016
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In: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 311:3, s. C452-C461
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Journal article (peer-reviewed)abstract
- Resting metabolic rate (RMR) in human shows pronounced individual variations, but the underlying molecular mechanism remains elusive. Cytochrome C oxidase (COX) plays a key role in control of metabolic rate and recent studies of the subunit 4 isoform 2 (COX IV-2) indicate involvement in the cellular response to hypoxia and oxidative stress. We evaluated whether the COX subunit IV isoform composition may explain the pronounced individual variations in resting metabolic rate (RMR). RMR was determined in healthy humans by indirect calorimetry and correlated to levels of COX IV-2 and COX IV-1 in Vastus Lateralis. Over expression and knock down of the COX IV isoforms were performed in primary myotubes followed by evaluation of the cell respiration and production of reactive oxygen species. Here we show that COX IV-2 protein is constitutively expressed in human skeletal muscle and strongly correlated to RMR. Primary human myotubes overexpressing COX IV-2 displayed markedly (>60%) lower respiration, reduced (>50%) cellular H2O2 production, higher resistance towards both oxidative stress and severe hypoxia compared to control cells. These results suggest an important role of isoform COX IV-2 in the control of energy expenditure, hypoxic tolerance and mitochondrial ROS homeostasis in humans.
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| 4. |
- Sundqvist, Michaela L, et al.
(author)
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A randomized clinical trial of the effects of leafy green vegetables and inorganic nitrate on blood pressure.
- 2020
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In: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 111:4, s. 749-756
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Journal article (peer-reviewed)abstract
- BACKGROUND: A diet rich in fruits and vegetables is associated with lowering of blood pressure (BP), but the nutrient(s) responsible for these effects remain unclear. Research suggests that inorganic nitrate present in leafy green vegetables is converted into NO in vivo to improve cardiovascular function.OBJECTIVE: In this study, we evaluated the effect of leafy green vegetables on BP in subjects with elevated BP, with the aim of elucidating if any such effect is related to their high nitrate content.DESIGN: We enrolled 243 subjects, 50-70 y old, with a clinic systolic BP (SBP) of 130-159 mm Hg. After a 2-wk run-in period on a nitrate-restricted diet the subjects were randomly assigned to receive 1 of the following 3 interventions daily for 5 wk: low-nitrate vegetables + placebo pills, low-nitrate vegetables + nitrate pills (300 mg nitrate), or leafy green vegetables containing 300 mg nitrate + placebo pills. The primary end point measure was the difference in change in 24 h ambulatory SBP between the groups.RESULTS: A total of 231 subjects (95%) completed the study. The insignificant change in ambulatory SBP (mean ± standard deviation) was -0.6 ± 6.2 mm Hg in the placebo group, -1.2 ± 6.8 mm Hg in the potassium nitrate group, and -0.5 ± 6.6 mm Hg in the leafy green vegetable group. There was no significant difference in change between the 3 groups.CONCLUSIONS: A 5-wk dietary supplementation with leafy green vegetables or pills containing the same amount of inorganic nitrate does not decrease ambulatory SBP in subjects with elevated BP. This trial was registered at clinicaltrials.gov as NCT02916615.
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| 5. |
- Sundqvist, Michaela L, et al.
(author)
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Renal handling of nitrate in women and men with elevated blood pressure.
- 2021
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In: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 232:1
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Journal article (peer-reviewed)abstract
- AIM: The inorganic anions nitrate and nitrite are oxidation products of nitric oxide (NO) that have often been used as an index of NO generation. More than just being surrogate markers of NO, nitrate/nitrite can recycle to bioactive NO again. Nitrate is predominantly eliminated via the kidneys; however, there is less knowledge regarding tubular handling. The aim of this study, as part of a large randomized controlled trial, was to explore potential sex differences in renal nitrate handling during low and high dietary nitrate intake. We hypothesized that renal clearance and excretion of nitrate are higher in men compared to women.METHODS: In prehypertensive and hypertensive individuals (n = 231), nitrate and nitrite were measured in plasma and urine at low dietary nitrate intake (baseline) and after 5 weeks supplementation with nitrate (300 mg potassium nitrate/day) or placebo (300 mg potassium chloride/day). Twenty-four hours ambulatory blood pressure recordings and urine collections were conducted.RESULTS: At baseline, plasma nitrate and nitrite, as well as the downstream marker of NO signalling cyclic guanosine monophosphate, were similar in women and men. Approximately 80% of filtered nitrate was spared by the kidneys. Urinary nitrate concentration, amount of nitrate excreted, renal nitrate clearance (Cnitrate ) and fractional excretion of nitrate (FEnitrate ) were lower in women compared to men. No association was observed between plasma nitrate concentrations and glomerular filtration rate (GFR), nor between FEnitrate and GFR in either sex. After 5 weeks of nitrate supplementation plasma nitrate and nitrite increased significantly, but blood pressure remained unchanged. FEnitrate increased significantly and the sex difference observed at baseline disappeared.CONCLUSION: Our findings demonstrate substantial nitrate sparing capacity of the kidneys, which is higher in women compared to men. This suggests higher tubular nitrate reabsorption in women but the underlying mechanism(s) warrants further investigation.
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| 6. |
- Yang, Jiangning, et al.
(author)
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Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP
- 2023
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In: Journal of Clinical Investigation. - : American Society For Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:17
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Journal article (peer-reviewed)abstract
- Red blood cells (RBCs) mediate cardioprotection via nitric oxide-like bioactivity, but the signaling and the identity of any mediator released by the RBCs remains unknown. We investigated whether RBCs exposed to hypoxia release a cardioprotective mediator and explored the nature of this mediator. Perfusion of isolated hearts subjected to ischemia-reperfusion with extracellular supernatant from mouse RBCs exposed to hypoxia resulted in improved postischemic cardiac function and reduced infarct size. Hypoxia increased extracellular export of cyclic guanosine monophosphate (cGMP) from mouse RBCs, and exogenous cGMP mimicked the cardioprotection induced by the supernatant. The protection induced by hypoxic RBCs was dependent on RBC-soluble guanylate cyclase and cGMP transport and was sensitive to phosphodiesterase 5 and activated cardiomyocyte protein kinase G. Oral administration of nitrate to mice to increase nitric oxide bioactivity further enhanced the cardioprotective effect of hypoxic RBCs. In a placebo-controlled clinical trial, a clear cardioprotective, soluble guanylate cyclase-dependent effect was induced by RBCs collected from patients randomized to 5 weeks nitrate-rich diet. It is concluded that RBCs generate and export cGMP as a response to hypoxia, mediating cardioprotection via a paracrine effect. This effect can be further augmented by a simple dietary intervention, suggesting preventive and therapeutic opportunities in ischemic heart disease.
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