scholarly journals Effects of sodium nitrite supplementation on vascular function and related small metabolite signatures in middle-aged and older adults

2016 ◽  
Vol 120 (4) ◽  
pp. 416-425 ◽  
Author(s):  
Allison E. DeVan ◽  
Lawrence C. Johnson ◽  
Forrest A. Brooks ◽  
Trent D. Evans ◽  
Jamie N. Justice ◽  
...  
Keyword(s):  
Older Adults ◽  
Endothelial Dysfunction ◽  
Carotid Artery ◽  
Endothelial Function ◽  
Sodium Nitrite ◽  
Metabolic Pathways ◽  
Vascular Function ◽  
Plasma Metabolites ◽  
Middle Aged ◽  
Plasma Nitrite

Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction and arterial stiffening with aging. Supplementation with sodium nitrite, a precursor of NO, ameliorates age-related vascular endothelial dysfunction and arterial stiffness in mice, but effects on humans, including the metabolic pathways altered, are unknown. The purpose of this study was to determine the safety, feasibility, and efficacy of oral sodium nitrite supplementation for improving vascular function in middle-aged and older adults and to identify related circulating metabolites. Ten weeks of sodium nitrite (80 or 160 mg/day, capsules, TheraVasc; randomized, placebo control, double blind) increased plasma nitrite acutely (5- to 15-fold, P < 0.001 vs. placebo) and chronically ( P < 0.10) and was well tolerated without symptomatic hypotension or clinically relevant elevations in blood methemoglobin. Endothelial function, measured by brachial artery flow-mediated dilation, increased 45-60% vs. baseline ( P < 0.10) without changes in body mass or blood lipids. Measures of carotid artery elasticity (ultrasound and applanation tonometry) improved (decreased β-stiffness index, increased cross-sectional compliance, P < 0.05) without changes in brachial or carotid artery blood pressure. Aortic pulse wave velocity was unchanged. Nitrite-induced changes in vascular measures were significantly related to 11 plasma metabolites identified by untargeted analysis. Baseline abundance of multiple metabolites, including glycerophospholipids and fatty acyls, predicted vascular changes with nitrite. This study provides evidence that sodium nitrite supplementation is well tolerated, increases plasma nitrite concentrations, improves endothelial function, and lessens carotid artery stiffening in middle-aged and older adults, perhaps by altering multiple metabolic pathways, thereby warranting a larger clinical trial.

scholarly journals Sodium Nitrite Supplementation Improves Vascular Endothelial Function but not Motor or Cognitive Function in Middle‐Aged and Older Adults

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Kayla A. Woodward ◽  
Jessica R. Santos‐Parker ◽  
Kara L. Lubieniecki ◽  
Erzsebet Nagy ◽  
Nathan S. Bryan ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Function ◽  
Endothelial Function ◽  
Sodium Nitrite ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Middle Aged

scholarly journals Undercarboxylated osteocalcin is associated with vascular function in female older adults but does not influence vascular function in male rabbit carotid artery ex vivo

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242774
Author(s):  
Alexander Tacey ◽  
Cassandra Smith ◽  
Mary N. Woessner ◽  
Paul Chubb ◽  
Christopher Neil ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Older Adults ◽  
Carotid Artery ◽  
Endothelial Function ◽  
Vascular Function ◽  
Ex Vivo ◽  
Atherogenic Diet ◽  
Undercarboxylated Osteocalcin ◽  
Menopausal Women ◽  
Post Menopausal

Background There are conflicting reports on the association of undercarboxylated osteocalcin (ucOC) in cardiovascular disease development, including endothelial function and hypertension. We tested whether ucOC is related to blood pressure and endothelial function in older adults, and if ucOC directly affects endothelial-mediated vasodilation in the carotid artery of rabbits. Methods In older adults, ucOC, blood pressure, pulse wave velocity (PWV) and brachial artery flow-mediated dilation (BAFMD) were measured (n = 38, 26 post-menopausal women and 12 men, mean age 73 ± 0.96). The vasoactivity of the carotid artery was assessed in male New Zealand White rabbits following a four-week normal or atherogenic diet using perfusion myography. An ucOC dose response curve (0.3–45 ng/ml) was generated following incubation of the arteries for 2-hours in either normal or high glucose conditions. Results ucOC levels were higher in normotensive older adults compared to those with stage 2 hypertension (p < 0.05), particularly in women (p < 0.01). In all participants, higher ucOC was associated with lower PWV (p < 0.05), but not BAFMD (p > 0.05). In rabbits, ucOC at any dose did not alter vasoactivity of the carotid artery, either following a normal or an atherogenic diet (p > 0.05). Conclusion Increased ucOC is associated with lower blood pressure and increased arterial stiffness, particularly in post-menopausal women. However, ucOC administration has no direct short-term effect on endothelial function in rabbit arteries. Future studies should explore whether treatment with ucOC, in vivo, has direct or indirect effects on blood vessel function.

scholarly journals Altered Purinergic Receptor Sensitivity in Type 2 Diabetes-Associated Endothelial Dysfunction and Up4A-Mediated Vascular Contraction

2018 ◽  
Vol 19 (12) ◽  
pp. 3942 ◽  
Author(s):  
Ali Mahdi ◽  
Tong Jiao ◽  
Yahor Tratsiakovich ◽  
Jiangning Yang ◽  
Claes-Göran Östenson ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Function ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Mesenteric Arteries ◽  
Vascular Contraction ◽  
Gk Rats ◽  
Vasoconstrictor Response

Purinergic signaling may be altered in diabetes accounting for endothelial dysfunction. Uridine adenosine tetraphosphate (Up4A), a novel dinucleotide substance, regulates vascular function via both purinergic P1 and P2 receptors (PR). Up4A enhances vascular contraction in isolated arteries of diabetic rats likely through P2R. However, the precise involvement of PRs in endothelial dysfunction and the vasoconstrictor response to Up4A in diabetes has not been fully elucidated. We tested whether inhibition of PRs improved endothelial function and attenuated Up4A-mediated vascular contraction using both aortas and mesenteric arteries of type 2 diabetic (T2D) Goto Kakizaki (GK) rats vs. control Wistar (WT) rats. Endothelium-dependent (EDR) but not endothelium-independent relaxation was significantly impaired in both aortas and mesenteric arteries from GK vs. WT rats. Non-selective inhibition of P1R or P2R significantly improved EDR in aortas but not mesenteric arteries from GK rats. Inhibition of A1R, P2X7R, or P2Y6R significantly improved EDR in aortas. Vasoconstrictor response to Up4A was enhanced in aortas but not mesenteric arteries of GK vs. WT rats via involvement of A1R and P2X7R but not P2Y6R. Depletion of major endothelial component nitric oxide enhanced Up4A-induced aortic contraction to a similar extent between WT and GK rats. No significant differences in protein levels of A1R, P2X7R, and P2Y6R in aortas from GK and WT rats were observed. These data suggest that altered PR sensitivity accounts for endothelial dysfunction in aortas in diabetes. Modulating PRs may represent a potential therapy for improving endothelial function.

Sleep deprivation and endothelial function: reconciling seminal evidence with recent perspectives

2021 ◽  
Vol 320 (1) ◽  
pp. H29-H35
Author(s):  
Joshua M. Cherubini ◽  
Jem L. Cheng ◽  
Jennifer S. Williams ◽  
Maureen J. MacDonald
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Sleep Deprivation ◽  
Vascular Function ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Health Concern ◽  
Short Sleep ◽  
Inadequate Sleep

Sleep is critical for the maintenance of physiological homeostasis and, as such, inadequate sleep beckons a myriad of pathologies. Sleep deprivation is a growing health concern in contemporary society since short sleep durations are associated with increased cardiovascular disease risk and atherosclerotic plaque development. Vascular endothelial dysfunction is an antecedent to atherosclerosis and cardiovascular disease. Herein, we review seminal literature indicating that short sleep durations attenuate endothelial function and explore more recent evidence indicating that sleep deprivation perturbs autonomic balance and the circadian rhythmicity of peripheral vascular clock components. We further examine literature that indicates a mechanistic link between short sleep duration and endothelial dysfunction and subsequent morbidity. Understanding the mechanisms that regulate endothelial function in the context of sleep deprivation facilitates the development and optimization of interventions, such as exercise, that mitigate the ramifications of inadequate sleep on vascular function and cardiovascular health. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/sleep-deprivation-and-endothelial-function/

scholarly journals The Efficacy of Stretching Exercises on Arterial Stiffness in Middle-Aged and Older Adults: A Meta-Analysis of Randomized and Non-Randomized Controlled Trials

2020 ◽  
Vol 17 (16) ◽  
pp. 5643 ◽  
Author(s):  
Michitaka Kato ◽  
Fumi Nihei Green ◽  
Kazuki Hotta ◽  
Toshiya Tsukamoto ◽  
Yasunari Kurita ◽  
...  
Keyword(s):  
Older Adults ◽  
Arterial Stiffness ◽  
Endothelial Function ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Middle Aged ◽  
Randomized Controlled ◽  
Stretching Exercises

Background: Aerobic exercise is known to reduce arterial stiffness; however, high-intensity resistance exercise is associated with increased arterial stiffness. Stretching exercises are another exercise modality, and their effect on arterial stiffness remains unclear. The purpose of this study was to determine whether stretching exercises reduce arterial stiffness in middle-aged and older adults, performing the first meta-analysis of currently available studies. Methods: We searched the literature for randomized controlled trials (RCTs) and non-RCTs published up to January 2020 describing middle-aged and older adults who participated in a stretching intervention vs. controls without exercise training. The primary and secondary outcomes were changes in arterial stiffness and vascular endothelial function and hemodynamic status. Pooled mean differences (MDs) and standard MDs (SMDs) with 95% confidence intervals (CIs) between the intervention and control groups were calculated using a random effects model. Results: We identified 69 trials and, after an assessment of relevance, eight trials, including a combined total of 213 subjects, were analyzed. Muscle stretching exercises were shown to significantly reduce arterial stiffness and improve vascular endothelial function (SMD: −1.00, 95% CI: −1.57 to −0.44, p = 0.0004; SMD: 1.15, 95% CI: 0.26 to 2.03, p = 0.01, respectively). Resting heart rate (HR) and diastolic blood pressure (DBP) decreased significantly after stretching exercise intervention (MD: −0.95 beats/min, 95% CI: −1.67 to −0.23 beats/min, p = 0.009; MD: −2.72 mm Hg, 95% CI: −4.01 to −1.43 mm Hg, p < 0.0001, respectively) Conclusions: Our analyses suggest that stretching exercises reduce arterial stiffness, HR, and DBP, and improve vascular endothelial function in middle-aged and older adults.

scholarly journals MnSOD protects against COX1-mediated endothelial dysfunction in chronic heart failure

2010 ◽  
Vol 298 (5) ◽  
pp. H1600-H1607 ◽  
Author(s):  
Jordan D. Miller ◽  
Veronica A. Peotta ◽  
Yi Chu ◽  
Robert M. Weiss ◽  
Kathy Zimmerman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Function ◽  
Manganese Superoxide Dismutase ◽  
Reduced Ejection Fraction ◽  
Manganese Superoxide ◽  
Cox Inhibitor

Endothelial function is impaired by oxidative stress in chronic heart failure (HF). Mechanisms that protect against increases in oxidative stress in HF are not clear. The goal of this study was to determine whether manganese superoxide dismutase (MnSOD) plays a key role in protecting against endothelial dysfunction in HF. Endothelial function and gene expression were examined in aorta from wild-type mice (MnSOD+/+) and mice deficient in MnSOD (MnSOD+/−) 12 wk after ligation of the left coronary artery (LCA). LCA ligation produced similar size myocardial infarctions in MnSOD+/+ and MnSOD+/− mice and reduced ejection fraction to ∼20% in both groups. Maximal relaxation in response to acetylcholine was 78 ± 3% (mean ± SE) and 66 ± 8% in sham-operated MnSOD+/+ and MnSOD+/− mice, respectively. Expression of antioxidant enzymes increased in MnSOD+/+ mice with HF, and maximal relaxation to acetylcholine was slightly impaired (68 ± 4%). Greater endothelial dysfunction was observed in MnSOD+/− mice with HF (46 ± 5%, P < 0.05), which was significantly improved by polyethylene glycol-catalase but not Tempol. Incubation with the nonspecific cyclooxygenase (COX) inhibitor indomethacin or the COX1 inhibitor valeryl salicylate, but not the COX-2 inhibitor NS-398, significantly improved relaxation to acetylcholine in HF mice (maximum relaxation = 74 ± 5, 91 ± 1, and 58 ± 5%). These data suggest that MnSOD plays a key role in protecting against endothelial dysfunction in HF. A novel mechanism was identified whereby chronic increases in oxidative stress, produced by mitochondrial SOD deficiency, impair vascular function via a hydrogen peroxide-dependent, COX1-dependent, endothelium-derived contracting factor.

scholarly journals Longer-Term Soy Nut Consumption Improves Vascular Function and Cardiometabolic Risk Markers in Older Adults: Results of a Randomized, Controlled Cross-Over Trial

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 58-58
Author(s):  
Lea Tischmann ◽  
Tanja Adam ◽  
Ronald Mensink ◽  
Peter Joris
Keyword(s):  
Older Adults ◽  
Arterial Stiffness ◽  
Endothelial Function ◽  
Vascular Function ◽  
Ldl Cholesterol ◽  
Control Period ◽  
Daily Intake ◽  
Cardiometabolic Health ◽  
Cvd Risk ◽  
Randomized Controlled

Abstract Objectives Soy foods may contribute to the beneficial effects of plant-based diets on cardiovascular disease (CVD) risk. However, their effects on vascular function have hardly been investigated. The objective was to investigate if longer-term soy nut consumption improves vascular function and cardiometabolic health in older adults. Methods Twenty-three apparently healthy participants (60–70 years; BMI between 20–30 kg/m2) participated in a randomized, controlled, single-blinded cross-over trial with an intervention (67 g of soy nuts daily providing 25.5 g soy protein) and control period (no nuts) of 16 weeks, separated by eight weeks wash-out. Volunteers followed the Dutch food-based dietary guidelines. At baseline and at 8 and 16 weeks anthropometric measurements and fasting blood samples were collected. Markers of vascular function (i.e., endothelial function, arterial stiffness, and microvascular structure) were assessed at week 16. Results No serious adverse events were reported and the soy nut regime was well tolerated. Body weight remained stable. Serum isoflavone concentrations, a marker of compliance, increased after the intervention period (daidzein: 128.3 ng/mL; 95% CI: 72.6–183.9 ng/mL; P &lt; 0.001 and genistein: 439.8 ng/mL 95% CI: 246.7–632.9 ng/mL; P &lt; 0.001). The brachial artery flow-mediated vasodilation (FMD) response increased by 1.49 pp (95% CI: 0.03–2.95 pp; P = 0.046) following the soy intervention, but no effect was found on the carotid artery reactivity (CAR) response. Arterial stiffness, assessed by carotid-to-femoral pulse wave velocity (PWVc-f), was unchanged. Retinal arteriolar calibers (CRAE), a measure for microvascular structure, tended to improve by 1.42 mm (95% CI: −0.05–2.90 mm; P = 0.059). Soy consumption also lowered serum LDL-cholesterol concentrations by 0.17 mmol/L (95% CI: 0.02–0.32 mmol/L; P = 0.027). HDL-cholesterol and triacylglycerol (TAG) did not change. Finally, office SBP and DBP decreased by 4 mmHg (95% CI: 0–8 mmHg; P = 0.034) and 2 mmHg (95% CI: 1–4 mmHg; P = 0.005), respectively. Conclusions A longer-term daily intake of soy nuts improved endothelial function, office blood pressure, and serum LDL-cholesterol concentrations, suggesting mechanisms by which an increased soy food intake beneficially affects CVD risk in older adults. Funding Sources This study was supported by a grant from the Alpro Foundation.

Sign in / Sign up

Export Citation Format

Share Document