Context Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear.Objective To determine effects of low doses of polyphenol-rich dark chocolate on BP.Design, Setting, and Participants Randomized, controlled, investigatorblinded, parallel-group trial involving 44 adults aged 56 through 73 years (24 women, 20 men) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006.Intervention Participants were randomly assigned to receive for 18 weeks either 6.3 g (30 kcal) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate.Main Outcome Measures Primary outcome measure was the change in BP after 18 weeks. Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide (S-nitrosoglutathione) and oxidative stress (8-isoprostane), and bioavailability of cocoa polyphenols. ResultsFrom baseline to 18 weeks, dark chocolate intake reduced mean (SD) systolic BP by −2.9 (1.6) mm Hg (PϽ.001) and diastolic BP by −1.9 (1.0) mm Hg (PϽ.001) without changes in body weight, plasma levels of lipids, glucose, and 8-isoprostane. Hypertension prevalence declined from 86% to 68%. The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 (0.12) nmol/L (PϽ.001), and a dark chocolate dose resulted in the appearance of cocoa phenols in plasma. White chocolate intake caused no changes in BP or plasma biomarkers.Conclusions Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide.

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Background: Epidemiological evidence suggests blood pressure-lowering effects of cocoa and tea. We undertook a meta-analysis of randomized controlled trials to determine changes in systolic and diastolic blood pressure due to the intake of cocoa products or black and green tea.Methods: MEDLINE, EMBASE, SCOPUS, Science Citation Index, and the Cochrane Controlled Trials Register were searched from 1966 until October 2006 for studies in parallel group or crossover design involving 10 or more adults in whom blood pressure was assessed before and after receiving cocoa products or black or green tea for at least 7 days.Results: Five randomized controlled studies of cocoa administration involving a total of 173 subjects with a median duration of 2 weeks were included. After the cocoa

Abstract-Short-term treatment of the endothelium with dihydropyridine calcium antagonists resulted in an increased release in NO that is not due to a modulation of L-type calcium channels, because macrovascular endothelial cells do not express this channel. We investigated whether long-term (48 hours) treatment of porcine endothelial cell cultures with the dihydropyridine calcium antagonist nifedipine resulted in a similar enhanced NO liberation. Regarding to the underlying mechanism, we examined whether (1) nifedipine changed the mRNA and protein levels of the constitutive endothelial NO synthase (NOS) in endothelial cell cultures or (2) nifedipine exerts an NO protective effect via its antioxidative properties, as revealed in a cell culture model and with native endothelium from porcine coronary arteries. ihydropyridine (DHP)-type calcium antagonists are important drugs in the treatment of hypertension and coronary heart disease. They induce their specific pharmacological effects by binding to L-type calcium channels, 1,2 which results in a reduced calcium influx with impaired electromechanical coupling both in vascular smooth muscle cells and in the heart. 3 A few years ago, however, it was observed that removal of the endothelium or blockade of the guanylate cyclase of the vessel wall reduced the efficacy of the DHP-induced vasorelaxation, 4 which indicated an endothelium-responsive cGMP-mediated process as part of the DHP action. Because macrovascular endothelial cells lack voltage-operated L-type calcium channels, 5,6 the DHPs must exert these effects via other mechanisms. In this context, it is worth mentioning that DHPs may also exert antihrombotic 7,8 and antiatherosclerotic 9,10 effects in different experimental and clinical settings, of which the underlying signal transduction remains obscure.With this background, it is tempting to speculate that NO, one of the most prominent endothelium-derived factors, 11,12 which relaxes smooth muscle cells via the cGMP signal cascade, 13 might be involved in these DHP actions. In fact, in various models, evidence has accumulated that DHPs stimulate the endothelial NO release, 14 -19 which may mediate or at least contribute to the abovementioned calcium channel-independent effects.Up to now, however, all of these findings were obtained only after acute exposure to DHPs (lasting minutes to hours). Because patients usually take calcium antagonists for a longer period of time, we investigated whether long-term treatment of endothelial cell cultures with nifedipine may alter the basal endothelial NO release as well as the expression of the constitutive endothelial NO synthase (ecNOS) mRNA and protein. Furthermore, because NO is rapidly deactivated by reactive oxygen species (ROS) 20 and the DHPs may act as scavengers as known from different in vitro models, [21][22][23] we also determined the antioxidative potency of nifedipine in endothelial cell cultures as well as in native cells to reveal a potential NO-protection effect as an underlying mechanism of the increased ...

The high intake of polyphenols is thought to contribute to the beneficial cardiovascular effects of plant-centered diets. A putative mechanism underlying the cardioprotective activity is thought to be a plant phenol-induced increase of nitric oxide formation by the constitutive endothelial nitric oxide synthase. Twenty-eight phenols of different classes commonly occurring in plant foods were examined for their capability of enhancing the endothelial nitric oxide release of isolated porcine coronary arteries by direct real-time measurement of the luminal surface nitric oxide concentration with an amperometric microsensor. Additionally, the relaxing activity of the phenols was measured on porcine coronary rings. Quercetin, myricetin, leucocyanidol, and oligomeric proanthocyanidins induced the highest increases in nitric oxide release (delta[NO] > 8.5 nM ); caffeic acid, fisetin, hyperosid, and isoquercitrin were moderately active (5 nM < delta[NO] < 8.5 nM ); the other phenolic compounds caused only marginal increases of the nitric oxide levels (delta[NO] < 5 nM). The nitric oxide-stimulating activity of the phenols was uniformly positively correlated with their vasorelaxing activity. However, endothelium-dependent vasorelaxations were limited to phenols inducing nitric oxide elevations > 5 nM (= Km value of the soluble guanylate cyclase). Analysis of structure-activity relations revealed that a high nitric oxide activity was confined to a flavan-moiety with free hydroxyl-residues at C3, C3', C4', C5, and C7 and a hydroxyl-, oxo-, or phenolic substituent at C4, whereas the caffeic acid scaffolding emerged as the minimally essential motif for the nitric oxide-dependent vasorelaxation.