Cocoa flavanols lower vascular arginase activity in human endothelial cells in vitro and in erythrocytes in vivo

Schnorr, Oliver; Brossette, Tatjana; Momma, Tony Y.; Kleinbongard, Petra; Keen, Carl L.; Schroeter, Hagen; Sies, Helmut

doi:10.1016/j.abb.2008.02.040

Cited by 120 publications

(80 citation statements)

References 34 publications

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“…Specifically, increased FMD resulting from cocoa/chocolate ingestion are reversed by NO synthase inhibition (16,22) and circulating biomarkers of NO synthesis are increased (19,22,42). Additionally, flavanols appear to increase endothelial-derived NO synthase activity (30,35) and lower vascular arginase activity (39). If NO production was increased by cocoa, we have no evidence that this was mediated by an antioxidant effect of cocoa, as we observed no change in oxidized LDL levels.…”

Section: Variablecontrasting

confidence: 46%

Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults

Monahan

Feehan

Kunselman

et al. 2011

Journal of Applied Physiology

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Monahan KD, Feehan RP, Kunselman AR, Preston AG, Miller DL, Lott ME. Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults. J Appl Physiol 111: 1568 -1574. First published September 8, 2011 doi:10.1152/japplphysiol.00865.2011.-An inverse relation exists between intake of flavonoid-rich foods, such as cocoa, and cardiovascular-related mortality. Favorable effects of flavonoids on the endothelium may underlie these associations. We performed a randomized, double-blind, placebo-controlled study to test the hypothesis that acute cocoa ingestion dose dependently increases endothelium-dependent vasodilation, as measured by an increase in brachial artery flow-mediated dilation (FMD), in healthy older adults. Measurements were obtained before (preingestion) and after (1-and 2-h postingestion) ingestion of 0 (placebo), 2, 5, 13, and 26 g of cocoa in 23 adults (63 Ϯ 2 yr old, mean Ϯ SE). Changes in brachial artery FMD 1-and 2-h postingestion compared with preingestion were used to determine the effects of cocoa. FMD was unchanged 1 (⌬Ϫ0.3 Ϯ 0.2%)-and 2-h (⌬0.1 Ϯ 0.1%) after placebo (0 g cocoa). In contrast, FMD increased both 1-h postingestion (2 g cocoa ⌬0.0 Ϯ 0.2%, 5 g cocoa ⌬0.8 Ϯ 0.3%, 13 g cocoa ⌬1.0 Ϯ 0.3%, and 26 g cocoa ⌬1.6 Ϯ 0.3%: P Ͻ 0.05 compared with placebo for 5, 13, and 26 g cocoa) and 2-h postingestion (2 g cocoa ⌬0.5 Ϯ 0.3%, 5 g cocoa ⌬1.0 Ϯ 0.3%, 13 g cocoa ⌬1.4 Ϯ 0.2%, and 26 g cocoa ⌬2.5 Ϯ 0.4%: P Ͻ 0.05 compared with placebo for 5, 13, and 26 g cocoa) on the other study days. A serum marker of cocoa ingestion (total epicatechin) correlated with increased FMD 1-and 2-h postingestion (r ϭ 0.44 -0.48; both P Ͻ 0.05). Collectively, these results indicate that acute cocoa ingestion dose dependently increases brachial artery FMD in healthy older humans. These responses may help to explain associations between flavonoid intake and cardiovascular-related mortality in humans.flavonoid; flavanol; chocolate; endothelium; endothelial function THE ENDOTHELIUM CONTRIBUTES critically to cardiovascular homeostasis by influencing factors such as vascular tone, vascular permeability, platelet aggregation, and thrombosis. As abnormal function of the endothelium is a key event in the atherosclerotic process (15), it is not surprising that endothelial dysfunction is a hallmark feature of many cardiovascular disease states (33). Moreover, it is not surprising that aging, which is a primary risk factor for the development of cardiovascular disease and atherosclerosis (29,36), is associated with marked endothelial dysfunction. Specifically, in response to stimulation of the vascular endothelium via pharmacological substances, such as acetylcholine, or physiological stimuli, such as increases in vascular shear stress, a reduced endothelium-dependent vasodilatory response occurs in healthy older adults compared with healthy young adults (7,11,12,41). As low levels of brachial artery flow-mediated dilation (FMD), a commonly used method to assess endothelium-dependent vasodi...

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Section: Variablecontrasting

confidence: 46%

Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults

Monahan

Feehan

Kunselman

et al. 2011

Journal of Applied Physiology

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“…In particular, dark chocolate intake reduced mean SBP by 2.9 mmHg (p < 0.001) and DBP by 1.9 mmHg (p < 0.001); these results were accompanied by a sustained increase of S-nitrosoglutathione, a source of bioavailable NO, by 0.23 nmol/L (p < 0.001) (50). Flavanols, and particularly flavanol-rich cocoa, elevate NO bioavailability by both stimulating the NO synthase (eNOS) activity (82,83) and increasing the availability of l-arginine (via reduction of its degradation by arginase) (84). Furthermore, in a rat model, flavanols prevented the elevation of BP induced by l-nitroarginine methyl ester (l-NAME), a powerful inhibitor of NOS (83).…”

Section: Putative Mechanismsmentioning

confidence: 98%

Cocoa, Blood Pressure, and Vascular Function

et al. 2012

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Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function.

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“…Corroborating this, in vitro testing of ARG inhibition in HUVEC cells shows that both (−)-epicatechin and its mixture of flavanol metabolites exhibited effects, suggesting that after metabolisation, polyphenols can retain anti-ARG activity (at least under controlled conditions) [29].…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, Schnorr et al [29] performed a study regarding the action of a cocoa drink that was either poor (< 90 mg) or rich (985 mg) in flavanols. This mixture provided (−)-epicatechin (0.1 µM) and catechin (0.4 µM) as well as the metabolites epicatechin-7-β-glucuronide (0.25 µM), 4′-O-methyl-epicatechin (0.2 µM), and 4′-O-methyl-epicatechin-7-β-glucuronide (1.7 µM) (values of plasma concentration measured after 2 h of consumption of 200 mL of cocoa beverage that provided 2.6 µM of flavonoids) in healthy humans (2 days).…”

Section: Methodsmentioning

confidence: 99%

“…With regard to the latter point, special attention has been paid to substances belonging to the class of polyphenols [26,29,[34][35][36][37][38]. Therefore, this article presents recent research regarding the search for new ARG inhibitors derived from medicinal plants with a potential therapeutic application in the fight against diseases related to the development of ED, as well as seeking to increase interest in the development of promising drugs in this field.…”

Section: Introductionmentioning

confidence: 99%

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2018

Planta Med

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IntroductionSeveral diseases have been linked to the development of ED, such as atherosclerosis, hypercholesterolaemia, coronary disease, erectile dysfunction, asthma, renal failure, rheumatoid arthritis, periodontitis, psychiatric disorders, and cancer, as well as diseases with a high prevalence, such as diabetes (types 1 and 2) and SAH [1-9].The preservation of the endothelium is fundamental in maintaining the physiology of the vascular system (in the regulation of its tonus, the development of immune, structural, and proliferative functions, and interaction with other cellular types) and also in the prevention of the development/aggravation of diseases [10][11][12].

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Cocoa flavanols lower vascular arginase activity in human endothelial cells in vitro and in erythrocytes in vivo

Cited by 120 publications

References 34 publications

Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults

Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults

Cocoa, Blood Pressure, and Vascular Function

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