scholarly journals The Role of Dietary Nitrate and the Oral Microbiome on Blood Pressure and Vascular tone

2020 ◽  
pp. 1-53
Author(s):  
H.S. Alzahrani ◽  
K.G. Jackson ◽  
D.A. Hobbs ◽  
J.A. Lovegrove

Abstract There is increasing evidence for the health benefits of dietary nitrates including lowering blood pressure and enhancing cardiovascular health. Although commensal oral bacteria play an important role in converting dietary nitrate to nitrite, very little is known about the potential role of these bacteria in blood pressure regulation and maintenance of vascular tone. The main purpose of this review is to present the current evidence on the involvement of the oral microbiome in mediating the beneficial effects of dietary nitrate on vascular function and to identify sources of inter and intra-individual differences in bacterial composition. A systematic approach was used to identify the relevant articles published on PubMed and Web of Science in English from January 1950 until September 2019 examining the effects of dietary nitrate on oral microbiome composition and association with blood pressure and vascular tone. To date, only a limited number of studies have been conducted, with n=9 in humans and n=3 in animals focusing mainly on blood pressure. In general, elimination of oral bacteria with use of a chlorhexidine based antiseptic mouthwash reduced the conversion of nitrate to nitrite and was accompanied in some studies by an increase in blood pressure in normotensive subjects. In conclusion, our findings suggest that oral bacteria may play an important role in mediating the beneficial effects of nitrate-rich foods on blood pressure. Further human intervention studies assessing the potential effects of dietary nitrate on oral bacteria composition and relationship to real time measures of vascular function are needed, particularly in individuals with hypertension and those at risk of developing cardiovascular diseases.

2013 ◽  
Vol 26 (2) ◽  
pp. 210-222 ◽  
Author(s):  
Ditte A. Hobbs ◽  
Trevor W. George ◽  
Julie A. Lovegrove

Evidence has accumulated in recent years that suggests that nitrate from the diet, particularly vegetables, is capable of producing bioactive NO in the vasculature, following bioconversion to nitrite by oral bacteria. The aim of the present review was to consider the current body of evidence for potential beneficial effects of dietary nitrate on blood pressure and endothelial function, with emphasis on evidence from acute and chronic human intervention studies. The studies to date suggest that dietary nitrate acutely lowers blood pressure in healthy humans. An inverse relationship was seen between dose of nitrate consumed and corresponding systolic blood pressure reduction, with doses of nitrate as low as 3 mmol of nitrate reducing systolic blood pressure by 3 mmHg. Moreover, the current studies provide some promising evidence on the beneficial effects of dietary nitrate on endothelial function.In vitrostudies suggest a number of potential mechanisms by which dietary nitrate and its sequential reduction to NO may reduce blood pressure and improve endothelial function, such as: acting as a substrate for endothelial NO synthase; increasing vasodilation; inhibiting mitochondrial reactive oxygen species production and platelet aggregation. In conclusion, the evidence for beneficial effects of dietary nitrate on blood pressure and endothelial function is promising. Further long-term randomised controlled human intervention studies assessing the potential effects of dietary nitrate on blood pressure and endothelial function are needed, particularly in individuals with hypertension and at risk of CVD.


Author(s):  
Ilaria Del Gaudio ◽  
Luisa Rubinelli ◽  
Linda Sasset ◽  
Christian Wadsack ◽  
Timothy Hla ◽  
...  

Background Most of the circulating sphingosine‐1‐phosphate (S1P) is bound to ApoM (apolipoprotein M) of high‐density lipoprotein (HDL) and mediates many beneficial effects of HDL on the vasculature via G protein–coupled S1P receptors. HDL‐bound S1P is decreased in atherosclerosis, myocardial infarction, and diabetes mellitus. In addition to being the target, the endothelium is a source of S1P, which is transported outside of the cells by Spinster‐2, contributing to circulating S1P as well as to local signaling. Mice lacking endothelial S1P receptor 1 are hypertensive, suggesting a vasculoprotective role of S1P signaling. This study investigates the role of endothelial‐derived S1P and ApoM‐bound S1P in regulating vascular tone and blood pressure. Methods and Results ApoM knockout (ApoM KO) mice and mice lacking endothelial Spinster‐2 (ECKO‐Spns2) were infused with angiotensin II for 28 days. Blood pressure, measured by telemetry and tail‐cuff, was significantly increased in both ECKO‐Spns2 and ApoM KO versus control mice, at baseline and following angiotensin II. Notably, ECKO‐Spns2 presented an impaired vasodilation to flow and blood pressure dipping, which is clinically associated with increased risk for cardiovascular events. In hypertension, both groups presented reduced flow‐mediated vasodilation and some degree of impairment in endothelial NO production, which was more evident in ECKO‐Spns2. Increased hypertension in ECKO‐Spns2 and ApoM KO mice correlated with worsened cardiac hypertrophy versus controls. Conclusions Our study identifies an important role for Spinster‐2 and ApoM‐HDL in blood pressure homeostasis via S1P‐NO signaling and dissects the pathophysiological impact of endothelial‐derived S1P and ApoM of HDL‐bound S1P in hypertension and cardiac hypertrophy.


Author(s):  
Andrii Boguslavskyi ◽  
Sergiy Tokar ◽  
Oleksandra Prysyazhna ◽  
Olena Rudyk ◽  
David Sanchez-Tatay ◽  
...  

Background: Background: While it has long been recognized that smooth muscle Na/K ATPase (NKA) modulates vascular tone and blood pressure (BP), the role of its accessory protein phopholemman (PLM) has not been characterized. The aim of this study was to test the hypothesis that PLM phosphorylation regulates vascular tone in vitro and this mechanism plays an important role in modulation of vascular function and BP in experimental models in vivo and in man. Methods: Mouse studies : PLM knock-in mice (PLM 3SA ), in which PLM is rendered unphosphorylatable, were used to assess the role of PLM phosphorylation in vitro in aortic and mesenteric vessels using wire myography and membrane potential measurements. In vivo BP and regional blood flow were assessed using Doppler flow and telemetry in young (14-16 weeks) and old (57-60 weeks) wild-type (WT) and transgenic mice. Human studies : We searched human genomic databases for mutations in PLM in the region of the phosphorylation sites and performed analyses within two human data cohorts (UK Biobank and GoDARTS) to assess the impact of an identified SNP on BP. This SNP was expressed in HEK cells and its effect on PLM phosphorylation determined using Western Blotting. Results: PLM phosphorylation at Ser63 and Ser68 limited vascular constriction in response to phenylephrine. This effect was blocked by ouabain. Prevention of PLM phosphorylation in the PLM 3SA mouse profoundly enhanced vascular responses to PE both in vitro and in vivo . In ageing WT mice PLM was hypophosphorylated and this correlated with the development of ageing-induced essential hypertension. In man we identified a non-synonymous coding variant, single nucleotide polymorphism rs61753924, which causes the substitution R70C in PLM. In HEK cells the R70C mutation prevented PLM phosphorylation at Ser68. This variant's rare allele is significantly associated with increased BP in middle-aged men. Conclusions: These studies demonstrate the importance of PLM phosphorylation in the regulation of vascular tone and BP and suggest a novel mechanism, and therapeutic target, for ageing-induced essential hypertension in man.


Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1852 ◽  
Author(s):  
Amy Rees ◽  
Georgina Dodd ◽  
Jeremy Spencer

Research has suggested a number of beneficial effects arising from the consumption of dietary flavonoids, found in foods such as cocoa, apples, tea, citrus fruits and berries on cardiovascular risk factors such as high blood pressure and endothelial dysfunction. These effects are thought to have a significant impact upon both vascular and cerebrovascular health, ultimately with the potential to prevent cardiovascular and potentially neurodegenerative disease with a vascular component, for example vascular dementia. This review explores the current evidence for the effects of flavonoid supplementation on human endothelial function and both peripheral and cerebral blood flow (CBF). Evidence presented includes their potential to reduce blood pressure in hypertensive individuals, as well as increasing peripheral blood perfusion and promoting CBF in both healthy and at-risk populations. However, there is great variation in the literature due to the heterogeneous nature of the randomised controlled trials conducted. As such, there is a clear need for further research and understanding within this area in order to maximise potential health benefits.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Javier I. Ottaviani ◽  
Abigail Britten ◽  
Debora Lucarelli ◽  
Robert Luben ◽  
Angela A. Mulligan ◽  
...  

Abstract Flavan-3-ols are a group of bioactive compounds that have been shown to improve vascular function in intervention studies. They are therefore of great interest for the development of dietary recommendation for the prevention of cardio-vascular diseases. However, there are currently no reliable data from observational studies, as the high variability in the flavan-3-ol content of food makes it difficult to estimate actual intake without nutritional biomarkers. In this study, we investigated cross-sectional associations between biomarker-estimated flavan-3-ol intake and blood pressure and other CVD risk markers, as well as longitudinal associations with CVD risk in 25,618 participants of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort. High flavan-3-ol intake, achievable as part of an habitual diet, was associated with a significantly lower systolic blood pressure (− 1.9 (− 2.7; − 1.1) mmHg in men and − 2.5 (− 3.3; − 1.8) mmHg in women; lowest vs highest decile of biomarker), comparable to adherence to a Mediterranean Diet or moderate salt reduction. Subgroup analyses showed that hypertensive participants had stronger inverse association between flavan-3-ol biomarker and systolic blood pressure when compared to normotensive participants. Flavanol intake could therefore have a role in the maintenance of cardiovascular health on a population scale.


2011 ◽  
Vol 110 (4) ◽  
pp. 1013-1020 ◽  
Author(s):  
Shane A. Phillips ◽  
Emon Das ◽  
Jingli Wang ◽  
Kirkwood Pritchard ◽  
David D. Gutterman

Resistance and aerobic exercise is recommended for cardiovascular health and disease prevention. However, the accompanying increase in arterial pressure during resistance exercise may be detrimental to vascular health. This study tests the vascular benefits of aerobic compared with resistance exercise on preventing impaired vascular function induced by a single weight lifting session that is associated with acute hypertension. Healthy, lean sedentary (SED) subjects, weight lifters, runners (>15 miles/wk), and cross trainers (chronic aerobic and resistance exercisers), underwent a single progressive leg press weight lifting session with blood pressure measurements. Brachial artery flow-mediated vasodilation (FMD; an index of arterial endothelial function) was determined using ultrasonography immediately before and after weight lifting. Sublingual nitroglycerin (0.4 mg) was used to determine endothelium-independent dilation after weight lifting. All subjects were normotensive with similar blood pressure responses during exercise. Baseline FMD was lower in runners (5.4 ± 0.5%; n = 13) and cross trainers (4.44 ± 0.3%; n = 13) vs. SED (8.5 ± 0.8%; n = 13; P = 0.037). Brachial FMD improved in conditioned weight lifters (to 8.8 ± 0.9%; P = 0.007) and runners (to 7.6 ± 0.6%; P < 0.001) but not cross trainers (to 5.3 ± 0.6%; P = NS) after acute hypertension. FMD was decreased in SED (to 5.7 ± 0.4%; P = 0.019). Dilation to nitroglycerin was similar among groups. These data suggest that endothelial responses are maintained after exposure to a single bout of weight lifting in resistance and aerobic athletes. Resistance and aerobic exercise may confer similar protection against acute vascular insults such as exertional hypertension.


2011 ◽  
Vol 301 (2) ◽  
pp. H584-H591 ◽  
Author(s):  
Wei-Qi He ◽  
Yan-Ning Qiao ◽  
Cheng-Hai Zhang ◽  
Ya-Jing Peng ◽  
Chen Chen ◽  
...  

Vascular tone, an important determinant of systemic vascular resistance and thus blood pressure, is affected by vascular smooth muscle (VSM) contraction. Key signaling pathways for VSM contraction converge on phosphorylation of the regulatory light chain (RLC) of smooth muscle myosin. This phosphorylation is mediated by Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) but Ca2+-independent kinases may also contribute, particularly in sustained contractions. Signaling through MLCK has been indirectly implicated in maintenance of basal blood pressure, whereas signaling through RhoA has been implicated in salt-induced hypertension. In this report, we analyzed mice with smooth muscle-specific knockout of MLCK. Mesenteric artery segments isolated from smooth muscle-specific MLCK knockout mice (MLCKSMKO) had a significantly reduced contractile response to KCl and vasoconstrictors. The kinase knockout also markedly reduced RLC phosphorylation and developed force. We suggest that MLCK and its phosphorylation of RLC are required for tonic VSM contraction. MLCKSMKO mice exhibit significantly lower basal blood pressure and weaker responses to vasopressors. The elevated blood pressure in salt-induced hypertension is reduced below normotensive levels after MLCK attenuation. These results suggest that MLCK is necessary for both physiological and pathological blood pressure. MLCKSMKO mice may be a useful model of vascular failure and hypotension.


2019 ◽  
Vol 79 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Charlotte Elizabeth Louise Evans

Dietary fibre comprises many different, mainly plant-based, compounds that are not fully digested in the human gut. Insoluble fibres include cellulose, hemi-celluloses and lignin and soluble fibres include pectins, β-glucan and hydro-colloids. In the UK, the daily recommended amount has increased to 30 g but only 13 % of men and 4 % of women meet this recommendation. Currently the mean intake for adults is 21 g for men and 17 g for women. There is a wealth of epidemiological evidence based on systematic reviews of trials and cohorts to support the higher fibre recommendation. This includes evidence of reductions in the risk for CVD (both heart disease and stroke) and lower risk of type 2 diabetes, lower blood pressure, lower LDL-cholesterol, as well as some cancers. Beneficial effects of fibre operate via a diverse range of mechanisms throughout the digestive system including the mouth, stomach and small and large intestine; some of which are still not completely understood. The updated recommendation for fibre is a long way from a typical British diet and requires several daily portions of fruit and vegetables and wholegrain foods. Improving dietary fibre intakes will require a variety of actions and policies from stakeholders; however, there is currently more of a focus on reducing sugar than increasing fibre. In order to increase the number of adults meeting the fibre recommendation, social marketing and labelling of high-fibre foods are warranted as well as reformulation and wider availability of wholegrain versions of popular foods.


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3611
Author(s):  
Rocío González-Soltero ◽  
María Bailén ◽  
Beatriz de Lucas ◽  
Maria Isabel Ramírez-Goercke ◽  
Helios Pareja-Galeano ◽  
...  

Nitrate supplementation is an effective, evidence-based dietary strategy for enhancing sports performance. The effects of dietary nitrate seem to be mediated by the ability of oral bacteria to reduce nitrate to nitrite, thus increasing the levels of nitrite in circulation that may be further reduced to nitric oxide in the body. The gut microbiota has been recently implicated in sports performance by improving muscle function through the supply of certain metabolites. In this line, skeletal muscle can also serve as a reservoir of nitrate. Here we review the bacteria of the oral cavity involved in the reduction of nitrate to nitrite and the possible changes induced by nitrite and their effect on gastrointestinal balance and gut microbiota homeostasis. The potential role of gut bacteria in the reduction of nitrate to nitrite and as a supplier of the signaling molecule nitric oxide to the blood circulation and muscles has not been explored in any great detail.


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