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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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Acute consumption of flavanol-rich cocoa beverage improves attenuated cutaneous microvascular function in healthy young African Americans.
Kim, K, Brothers, RM
Microvascular research. 2020;:103931
Abstract
Flavanols have beneficial effects on vascular health and we have recently demonstrated that cerebral vasodilatory capacity in healthy young African Americans (AA) is improved with acute flavanol intake relative to aged-matched Caucasian Americans (CA). However, whether the positive benefits of acute flavanol consumption would also be present in the cutaneous microvascular circulation of AA remains unknown. Thus, we hypothesized that acute consumption of flavanol-rich cocoa (FC) would improve the previously reported reduced cutaneous microvascular responses to local heating in young AA. Seven AA and seven CA participated in this double-blind crossover study. Data were collected on two different days, separated by a minimum of one week. Two intradermal microdialysis membranes were inserted in the forearm and each site was randomly assigned to receive lactated Ringer's solution or NO synthase (NOS) inhibitor. Participants were randomly assigned to consume either a non-flavanol containing (NF) beverage or FC beverage. Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flux/mean arterial pressure and normalized as % maximal CVC (%CVCmax). The difference in %CVCmax between the Ringer's site and NOS inhibited site was calculated to assess NO contribution (Δ %CVCmax). In the Ringer's site, acute consumption of FC beverage improved %CVCmax during 39 °C heating when compared to NF beverage in AA (NF: 36 ± 6 vs. FC: 47 ± 5%CVCmax; P < .01) while there was similar %CVCmax during 39 °C heating between beverages in CA (NF: 55 ± 4 vs. FC: 59 ± 5%CVCmax; P = .40). During 39 °C heating, NO contribution was significantly higher with FC beverage than NF beverage in AA (NF: 27 ± 5 vs. FC: 35 ± 4 Δ %CVCmax; P = .03) while there was similar NO contribution between beverages in CA (NF: 42 ± 4 vs. FC: 45 ± 4 Δ %CVCmax; P = .36). This data suggests that acute consumption of FC could be a therapeutic solution to improve an attenuated microvascular function in young AA.
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Increased fractalkine and vascular dysfunction in obesity and in type 2 diabetes. Effects of oral antidiabetic treatment.
Schinzari, F, Tesauro, M, Campia, U, Cardillo, C
Vascular pharmacology. 2020;:106676
Abstract
Activation of fractalkine and other chemokines plays an important role in atherogenesis and, in conjunction with endothelial dysfunction, promotes premature vascular damage in obesity and diabetes. We hypothesized that increased circulating fractalkine coexists with impaired vasomotor function in metabolically healthy or unhealthy obesity, and that treatment with antidiabetic drugs may impact these abnormalities in type 2 diabetes. Compared to lean subjects, in both obese groups the vasodilator responses to acetylcholine and sodium nitroprusside were impaired (both P < .001); ETA-receptor blockade resulted in greater vasodilation (both P < .001); and plasma levels of fractalkine, E-selectin and monocyte chemoattractant protein (MCP)-1 were increased (all P < .05). In diabetic patients, oral antidiabetic drugs (glyburide, metformin or pioglitazone) reduced circulating levels fractalkine and E-selectin (both P < .05), without affecting vascular responses (all P > .05). Our findings indicate that insulin resistant states are associated with elevated atherogenic chemokines and impaired vascular reactivity. Antidiabetic treatment results in lower circulating fractalkine, which may provide cardiovascular benefits.
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Cocoa might improve walking performance in PAD.
Huynh, K
Nature reviews. Cardiology. 2020;(5):266
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Vitamin D deficiency in association with endothelial dysfunction: Implications for patients with COVID-19.
Zhang, J, McCullough, PA, Tecson, KM
Reviews in cardiovascular medicine. 2020;(3):339-344
Abstract
There is emerging evidence to suggest that vitamin D deficiency is associated with adverse outcomes in COVID-19 patients. Conversely, vitamin D supplementation protects against an initial alveolar diffuse damage of COVID-19 becoming progressively worse. The mechanisms by which vitamin D deficiency exacerbates COVID-19 pneumonia remain poorly understood. In this review we describe the rationale of the putative role of endothelial dysfunction in this event. Herein, we will briefly review (1) anti-inflammatory and anti-thrombotic effects of vitamin D, (2) vitamin D receptor and vitamin D receptor ligand, (3) protective role of vitamin D against endothelial dysfunction, (4) risk of vitamin D deficiency, (5) vitamin D deficiency in association with endothelial dysfunction, (6) the characteristics of vitamin D relevant to COVID-19, (7) the role of vitamin D on innate and adaptive response, (8) biomarkers of endothelial cell activation contributing to cytokine storm, and (9) the bidirectional relationship between inflammation and homeostasis. Finally, we hypothesize that endothelial dysfunction relevant to vitamin D deficiency results from decreased binding of the vitamin D receptor with its ligand on the vascular endothelium and that it may be immune-mediated via increased interferon 1 α. A possible sequence of events may be described as (1) angiotensin II converting enzyme-related initial endothelial injury followed by vitamin D receptor-related endothelial dysfunction, (2) endothelial lesions deteriorating to endothelialitis, coagulopathy and thrombosis, and (3) vascular damage exacerbating pulmonary pathology and making patients with vitamin D deficiency vulnerable to death.
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Effects of Oral Magnesium Supplementation on Vascular Function: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Marques, BCAA, Klein, MRST, da Cunha, MR, de Souza Mattos, S, de Paula Nogueira, L, de Paula, T, Corrêa, FM, Oigman, W, Neves, MF
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension. 2020;(1):19-28
Abstract
INTRODUCTION The effects of magnesium (Mg) supplementation on vascular function have been evaluated in some randomized controlled trials (RCT) but their results are conflicting. AIM: A systematic review and meta-analysis were conducted to summarize the effects of oral Mg supplementation on vascular function in RCT. METHODS The databases MEDLINE (PubMed), Embase, Web of Science and Cochrane Library were accessed from inception to May 27, 2019. Intergroup differences (treatment vs. control group) related to changes in flow-mediated dilation (FMD) and pulse wave velocity (PWV), expressed as mean and standard deviation, were used to evaluate the effect of Mg supplementation on these outcomes. The results of the meta-analysis were expressed using a random-effects model. The heterogeneity between studies was evaluated using the I2 statistic. RESULTS The oral supplementation of Mg had no significant effect on FMD (mean difference 2.13; 95% CI - 0.56, 4.82; p = 0.12) and PWV (mean difference - 0.54, 95% CI - 1.45, 0.36, p = 0.24). Heterogeneity for both outcomes (FMD and PWV) was high (I2 = 99%, p < 0.001). However, in subgroup analyses, oral Mg significantly improved FMD in studies longer than 6 months, in unhealthy subjects, in individuals older than 50 years, or in those with body mass index (BMI) ≥ 25 kg/m2. The reduced number of RCT and the heterogeneity among them were the main limitations. CONCLUSIONS This meta-analysis suggest that oral Mg supplementation may improve endothelial function when conducted at least for 6 months and in unhealthy, overweight or older individuals. Registration number: PROSPERO CRD42019111462.
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Dietary nitrate does not acutely enhance skeletal muscle blood flow and vasodilation in the lower limbs of older adults during single-limb exercise.
Hughes, WE, Kruse, NT, Ueda, K, Feider, AJ, Hanada, S, Bock, JM, Casey, DP
European journal of applied physiology. 2020;(6):1357-1369
Abstract
PURPOSE Blood flow (BF) and vasodilator responses to knee-extension exercise are attenuated in older adults across an exercise transient (onset, kinetics, and steady-state), and reduced nitric oxide bioavailability (NO) has been hypothesized to be a primary mechanism contributing to this attenuation. We tested the hypothesis acute dietary nitrate (NO3-) supplementation (~ 4.03 mmol NO3- and 0.29 mmol NO2-) would improve leg vasodilator responses across an exercise transient during lower limb exercise in older adults. METHODS Older (n = 10) untrained adults performed single and rhythmic knee-extension contractions at 20% and 40% work-rate maximum (WRmax) prior to and 2-h after consuming a NO3- or placebo beverage in a double-blind, randomized fashion. Femoral artery BF was measured by Doppler ultrasound. Vascular conductance was calculated using BF and mean arterial pressure. RESULTS Acute ingestion of dietary NO3- enhanced plasma [NO3-] and [NO2-] (P < 0.05). Neither dietary NO3- or placebo enhanced vasodilator responses at the onset of exercise or during steady state at 20% and 40% WRmax (P > 0.05). Leg vasodilator kinetics during rhythmic exercise remained unchanged following NO3- and placebo ingestion (P > 0.05). CONCLUSIONS The key findings of this study are that despite increasing plasma [NO3-] and [NO2-], acute dietary NO3- intake had no effect on (1) rapid hyperaemic or vasodilator responses at the onset of exercise; (2) hyperaemic and vasodilator responses during steady-state submaximal exercise; or (3) kinetics of vasodilation preceding steady-state responses. Collectively, these findings suggest that low dose dietary NO3- supplementation does not improve hyperaemic and vasodilator responses across an exercise transient in older adults.
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A Paradoxical Vasodilatory Nutraceutical Intervention for Prevention and Attenuation of Migraine-A Hypothetical Review.
Chaliha, DR, Vaccarezza, M, Takechi, R, Lam, V, Visser, E, Drummond, P, Mamo, JCL
Nutrients. 2020;(8)
Abstract
Studies suggest that migraine pain has a vascular component. The prevailing dogma is that peripheral vasoconstriction activates baroreceptors in central, large arteries. Dilatation of central vessels stimulates nociceptors and induces cortical spreading depression. Studies investigating nitric oxide (NO) donors support the indicated hypothesis that pain is amplified when acutely administered. In this review, we provide an alternate hypothesis which, if substantiated, may provide therapeutic opportunities for attenuating migraine frequency and severity. We suggest that in migraines, heightened sympathetic tone results in progressive central microvascular constriction. Suboptimal parenchymal blood flow, we suggest, activates nociceptors and triggers headache pain onset. Administration of NO donors could paradoxically promote constriction of the microvasculature as a consequence of larger upstream central artery vasodilatation. Inhibitors of NO production are reported to alleviate migraine pain. We describe how constriction of larger upstream arteries, induced by NO synthesis inhibitors, may result in a compensatory dilatory response of the microvasculature. The restoration of central capillary blood flow may be the primary mechanism for pain relief. Attenuating the propensity for central capillary constriction and promoting a more dilatory phenotype may reduce frequency and severity of migraines. Here, we propose consideration of two dietary nutraceuticals for reducing migraine risk: L-arginine and aged garlic extracts.
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Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.
Papp, Z, Agostoni, P, Alvarez, J, Bettex, D, Bouchez, S, Brito, D, Černý, V, Comin-Colet, J, Crespo-Leiro, MG, Delgado, JF, et al
Journal of cardiovascular pharmacology. 2020;(1):4-22
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Abstract
Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.
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Acute Exenatide Therapy Attenuates Postprandial Vasodilation in Humans with Prediabetes: A Randomized Controlled Trial.
Hamidi, V, Riggs, K, Zhu, L, Bermudez Saint Andre, K, Westby, C, Coverdale, S, Dursteler, A, Wang, H, Miller Iii, C, Taegtmeyer, H, et al
Metabolic syndrome and related disorders. 2020;(5):225-233
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Abstract
Background: The state of prediabetes comprises atherosclerotic changes leading to decreased vascular function in humans. This study examined the effects on incretin mimetics on vascular physiology in the prediabetic postprandial state. Methods: Fifteen obese adults with prediabetes participated in a randomized, crossover, double-blinded trial comparing the postprandial effects of exenatide, saxagliptin, and placebo on peripheral vasodilation. All studies utilized a standardized high-fat meal. Resting and peak forearm blood flow (FBF) were measured via strain gauge venous occlusion plethysmography, and makers of vascular dysfunction were measured in plasma. Results: Exenatide attenuated resting FBF at 3 hr (P = 0.003) and 6 hr (P = 0.056) postmeal, compared to placebo. Nonsignificant reductions in resting FBF were observed between saxagliptin and placebo at the same time points. No group differences were observed for peak FBF, plasma nitrotyrosine, and plasma 8-iso-prostaglandin F2alpha. A transient increase in plasma triglyceride was abated in the exenatide group, when compared to saxagliptin and placebo groups. Only exenatide group showed no significant upsurge in plasma insulin. Plasma-free fatty acids significantly declined in all three groups, although less markedly for exenatide. Postmeal glucose increased at 2 hr with placebo and saxagliptin, but simultaneously decreased with exenatide. Conclusions: Acute treatment with exenatide blunted the postprandial vasodilatory effect of a high-fat meal in prediabetes. Exenatide's acute effects derived primarily from multiple endothelium-independent processes. Trial Registration Number: NCT02104739.