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1.
Acute resveratrol supplementation in coronary artery disease: towards patient stratification.
Diaz, M, Avila, A, Degens, H, Coeckelberghs, E, Vanhees, L, Cornelissen, V, Azzawi, M
Scandinavian cardiovascular journal : SCJ. 2020;(1):14-19
Abstract
Objective: Resveratrol (RV) is a polyphenol with antioxidant, anti-inflammatory and cardio-protective properties. Our objective was to investigate whether acute supplementation with high doses of RV would improve flow-mediated dilation (FMD) and oxygen consumption (VO2) kinetics in older coronary artery disease (CAD) patients. Design: We employed a placebo-controlled, single-blind, crossover design in which ten participants (aged 66.6 ± 7.8 years) received either RV or placebo (330 mg, 3× day-1) during three consecutive days plus additional 330 mg in the morning of the fourth day with a seven-day wash-out period in-between. On the fourth day, FMD of the brachial artery and VO2 on-kinetics were determined. Results: RV improved FMD in patients who had undergone coronary artery bypass grafting (CABG; -1.4 vs. 5.0%; p = .004), but not in those who had undergone percutaneous coronary intervention (PCI; 4.2 vs. -0.2%; NS). Conclusion: Acute high dose supplementation with RV improved FMD in patients after CABG surgery but impaired FMD in patients who underwent PCI. The revascularization method-related differential effects of RV may be due to its direct effects on endothelial-dependent dilator responses. Our findings have important implications for personalized treatment and stratification of older CAD patients.
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2.
Dilatation of Retinal Arterioles Induced by Topical Dorzolamide for One Week Is Impaired in Patients with Type 1 Diabetes and Mild Retinopathy.
Tilma, KK, Bek, T
Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde. 2020;(3):236-242
Abstract
BACKGROUND Diabetic retinopathy is characterised by morphological lesions in the retina secondary to disturbances in retinal blood flow. Previous studies have shown that the carbonic anhydrase inhibitor (CAI) dorzolamide can induce immediate dilatation of retinal arterioles and a sustained increase in retinal blood flow in primary open-angle glaucoma. However, the effect of sustained treatment with CAI on retinal arterioles in normal persons and in patients with diabetic retinopathy is unknown. METHODS The Dynamic Vessel Analyzer was used to assess the baseline diameter and the diameter response of retinal arterioles during an increase in arterial blood pressure induced by isometric exercise and during flicker stimulation before and 2 h, 24 h and 1 week after onset of topical treatment with dorzolamide. At each examination the diameter responses were studied before and during breathing in of a hypercapnic gas mixture. RESULTS Treatment with dorzolamide for 1 week significantly increased the diameter of retinal arterioles in normal persons, and breathing in of a hypercapnic gas mixture reduced this response. The pathological vasodilatation and reduced retinal autoregulation in patients with diabetic retinopathy were unaffected by dorzolamide and hypercapnia. CONCLUSIONS The study suggests a lack of relevance of CAI for the treatment of pathological vasodilatation in early diabetic retinopathy.
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3.
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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4.
Effect of 6 wk of high-intensity one-legged cycling on functional sympatholysis and ATP signaling in patients with heart failure.
Munch, GW, Iepsen, UW, Ryrsø, CK, Rosenmeier, JB, Pedersen, BK, Mortensen, SP
American journal of physiology. Heart and circulatory physiology. 2018;(3):H616-H626
Abstract
Breathlessness during daily activities is the primary symptom in patients with heart failure (HF). Poor correlation between the hemodynamic parameters of left ventricular performance and perceived symptoms suggests that other factors, such as skeletal muscle function, play a role in determining exercise capacity. We investigated the effect of 6 wk of high-intensity, one-legged cycling (HIC; 8 × 4 at 90% one-legged cycling max) on 1) the ability to override sympathetic vasoconstriction (arterial infusion of tyramine) during one-legged knee-extensor exercise (KEE), 2) vascular function (arterial infusion of ACh, sodium nitroprusside, tyramine, and ATP), and 3) exercise capacity in HF patients with reduced ejection fraction ( n = 8) compared with healthy individuals ( n = 6). Arterial tyramine infusion lowered leg blood flow and leg vascular conductance at rest and during KEE before the training intervention in both groups ( P < 0.05) but not during KEE after the training intervention. There was no difference between groups. The peak vasodilatory response to ATP was blunted in HF patients ( P < 0.05), whereas there was no difference in ACh- and sodium nitroprusside-induced vasodilation between HF patients and healthy individuals. ACh-induced vasodilation increased in HF patients after the training intervention ( P < 0.05). HIC improved aerobic capacity in both groups ( P < 0.05), whereas only HF patients made improvements in the 6-min walking distance ( P < 0.05). These results suggest that exercise hyperemia and functional sympatholysis are not altered in HF patients and that functional sympatholysis is improved with HIC in both HF patients and healthy individuals. Moreover, these results suggest that the peak vasodilatory response to ATP is blunted in HF. NEW & NOTEWORTHY The ability to override sympathetic vasoconstrictor activity (by arterial tyramine infusion) during exercise is not different between heart failure patients and healthy individuals and is improved by high-intensity, one-legged cycling training. The peak vasodilatory response to ATP is reduced in heart failure patients.
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5.
The impact of an acute oral phosphate load on endothelium dependent and independent brachial artery vasodilation in healthy males.
Levac, BM, Adams, MA, Pyke, KE
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2017;(12):1307-1315
Abstract
Serum phosphate levels are associated with cardiovascular morbidity and mortality in the general population and endothelial dysfunction may be mechanistically involved. The purpose of this study was to investigate the effects of acute phosphate supplementation on endothelial-dependent (flow-mediated dilation; FMD) and -independent (glyceryl trinitrate; GTN)) vasodilation in young, healthy males. Seventeen healthy male participants (age, 23 ± 3 years) were exposed to an oral load of phosphate (PHOS; liquid supplement containing 1200 mg of phosphorous) and placebo (PLAC) over 2 experimental days. A brachial artery FMD test was performed pre-ingestion and at 20 min, 60 min, and 120 min following the ingestion of the phosphate load or the placebo. GTN tests were performed pre- and 140 min post-ingestion. Serum phosphate was not impacted differently by phosphate versus placebo ingestion (p = 0.780). In contrast, urinary phosphate excretion was markedly increased in the PHOS (p < 0.001) but not in the PLAC condition (p = 0.130) (Δ fractional excretion of phosphate in PHOS (29.2%) vs. PLAC (9.3%)). This indicates that circulating phosphate levels were homeostatically regulated. GTN-mediated vasodilation was not significantly affected by phosphate ingestion. In primary analysis no impact of phosphate ingestion on FMD was detected. However, when the shear stress stimulus was added as a covariate in a subset of participants, exploratory pairwise comparisons revealed a significantly lower FMD 20 min post-phosphate ingestion versus placebo (p = 0.024). The effects of phosphate ingestion on FMD and serum phosphate are in contrast with previous findings and the mechanisms that underlie the disparate results require further investigation.
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6.
Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion.
Limberg, JK, Kellawan, JM, Harrell, JW, Johansson, RE, Eldridge, MW, Proctor, LT, Sebranek, JJ, Schrage, WG
American journal of physiology. Heart and circulatory physiology. 2014;(6):H840-7
Abstract
We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise - rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = -0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA.
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7.
Effects of GLP-1 on forearm vasodilator function and glucose disposal during hyperinsulinemia in the metabolic syndrome.
Tesauro, M, Schinzari, F, Adamo, A, Rovella, V, Martini, F, Mores, N, Barini, A, Pitocco, D, Ghirlanda, G, Lauro, D, et al
Diabetes care. 2013;(3):683-9
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Abstract
OBJECTIVE Patients with the metabolic syndrome (MetS) have impaired insulin-induced enhancement of vasodilator responses. The incretin hormone glucagon-like peptide 1 (GLP-1), beyond its effects on blood glucose, has beneficial actions on vascular function. This study, therefore, aimed to assess whether GLP-1 affects insulin-stimulated vasodilator reactivity in patients with the MetS. RESEARCH DESIGN AND METHODS Forearm blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in MetS patients before and after the addition of GLP-1 to an intra-arterial infusion of saline (n = 5) or insulin (n = 5). The possible involvement of oxidative stress in the vascular effects of GLP-1 in this setting was investigated by infusion of vitamin C (n = 5). The receptor specificity of GLP-1 effect during hyperinsulinemia was assessed by infusing its metabolite GLP-1(9-36) (n = 5). The metabolic actions of GLP-1 were also tested by analyzing forearm glucose disposal during hyperinsulinemia (n = 5). RESULTS In MetS patients, GLP-1 enhanced endothelium-dependent and -independent responses to ACh and SNP, respectively, during hyperinsulinemia (P < 0.001 for both), but not during saline (P > 0.05 for both). No changes in vasodilator reactivity to ACh and SNP were seen after GLP-1 was added to insulin and vitamin C (P > 0.05 for both) and after GLP-1(9-36) was given during hyperinsulinemia (P > 0.05 for both). Also, GLP-1 did not affect forearm glucose extraction and uptake during hyperinsulinemia (P > 0.05 for both). CONCLUSIONS In patients with the MetS, GLP-1 improves insulin-mediated enhancement of endothelium-dependent and -independent vascular reactivity. This effect may be influenced by vascular oxidative stress and is possibly exerted through a receptor-mediated mechanism.
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Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women.
Akazawa, N, Choi, Y, Miyaki, A, Tanabe, Y, Sugawara, J, Ajisaka, R, Maeda, S
Nutrition research (New York, N.Y.). 2012;(10):795-9
Abstract
Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function.
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Chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation in middle-aged humans.
Holowatz, LA, Kenney, WL
Journal of applied physiology (Bethesda, Md. : 1985). 2009;(2):500-5
Abstract
Full expression of reflex cutaneous vasodilation is dependent on cyclooxygenase- (COX) and nitric oxide synthase- (NOS) dependent mechanisms. Low-dose aspirin therapy is widely prescribed to inhibit COX-1 in platelets for atherothrombotic prevention. We hypothesized that chronic COX inhibition with daily low-dose aspirin therapy (81 mg) would attenuate reflex vasodilation in healthy human skin. Two microdialysis fibers were placed in forearm skin of seven middle-aged (57 +/- 3 yr), normotensive, healthy humans with no preexisting cardiovascular disease, taking daily low-dose aspirin therapy (aspirin: 81 mg), and seven unmedicated, healthy, age-matched control (no aspirin, 55 +/- 3 yr) subjects, with one site serving as a control (Ringer) and the other NOS inhibited (NOS inhibited: 10 mM N(G)-nitro-l-arginine methyl ester). Red cell flux was measured over each site by laser-Doppler flowmetry, as reflex vasodilation was induced by increasing core temperature (oral temperature) 1.0 degrees C using a water-perfused suit. Cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure) and normalized to maximal CVC (CVC(max); 28 mM sodium nitroprusside). CVC(max) was not affected by either aspirin or NOS inhibition. The plateau in cutaneous vasodilation during heating (change in oral temperature = 1.0 degrees C) was significantly attenuated in the aspirin group (aspirin: 25 +/- 3% CVC(max) vs. no aspirin: 50 +/- 7% CVC(max), P < 0.001 between groups). NOS inhibition significantly attenuated %CVC(max) in both groups (aspirin: 17 +/- 2% CVC(max), no aspirin: 23 +/- 3% CVC(max); P < 0.001 vs. control), but this attenuation was less in the no-aspirin treatment group (P < 0.001). This is the first observation that chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation through both COX- and NOS-dependent mechanisms.
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Effect of acute changes in oxygen tension on flow-mediated dilation. Relation to cardivascular risk.
Frøbert, O, Holmager, P, Jensen, KM, Schmidt, EB, Simonsen, U
Scandinavian cardiovascular journal : SCJ. 2008;(1):38-47
Abstract
OBJECTIVE Oxygen-dependent changes in vascular diameters may be detrimental when the endothelium is dysfunctional. DESIGN Endothelial responsiveness was evaluated by brachial ultrasound and flow-mediated/nitroglycerin-mediated dilation (FMD/NMD). FMD/NMD was investigated in males with increased risk of cardiovascular disease (mean age 44+/-2 years, n=10) and matched controls without risk factors (44+/-2 years, n=10). FMD/NMD was assessed during normoxia (21% O2, 79% N2), while inhaling hypoxic gas (12.5% O2, FMDHyp/NMD), and 100% O2 supplementation (FMDO2/NMD). In a second study we addressed the effect of lipid lowering. Twenty persons with cardiovascular risk (mean age 50+/-2 years) were treated with atorvastatin (80 mg/day) and FMD/NMD was measured during normoxia, hypoxia and oxygen supplementation before, after 1 day and 3 months. RESULTS Oxygen supplementation evoked vasoconstriction, while FMDHyp/NMD was reduced compared to FMD/NMD. Atorvastatin significantly lowered total cholesterol, LDL cholesterol, and ADMA after 1 day of treatment, while triglycerides, ApoB and hsCRP were lowered after 3 months. Atorvastatin did not change FMD/NMD irrespective of oxygen tension. CONCLUSION Irrespective of risk factors or atorvastatin, hypoxia reduced endothelial vasodilation while oxygen supplementation evoked vasoconstriction.