The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies.

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 vitro studies 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.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Casein-derived lactotripeptides reduce systolic and diastolic blood pressure in a meta-analysis of randomised clinical trials

There is an urgent need to treat individuals with high blood pressure (BP) with effective dietary strategies. Previous studies suggest a small, but significant decrease in BP after lactotripeptides (LTP) ingestion, although the data are inconsistent. The study aim was to perform a comprehensive meta-analysis of data from all relevant randomised controlled trials (RCT). Medline, Cochrane library, EMBASE and Web of Science were searched until May 2014. Eligibility criteria were RCT that examined the effects of LTP on BP in adults, with systolic BP (SBP) and diastolic BP (DBP) as outcome measures. Thirty RCT met the inclusion criteria, which resulted in 33 sets of data. The pooled treatment effect for SBP was −2.95 mmHg (95% CI: −4.17, −1.73; p < 0.001), and for DBP was −1.51 mmHg (95% CI: −2.21, −0.80; p < 0.001). Sub-group analyses revealed that reduction of BP in Japanese studies was significantly greater, compared with European studies (p = 0.002 for SBP and p < 0.001 for DBP). The 24-h ambulatory BP (AMBP) response to LTP supplementation was statistically non-significant (p = 0.101 for SBP and p = 0.166 for DBP). Both publication bias and “small-study effect” were identified, which shifted the treatment effect towards less significant SBP and non-significant DBP reduction after LTP consumption. LTP may be effective in BP reduction, especially in Japanese individuals; however sub-group, meta-regression analyses and statistically significant publication biases suggest inconsistencies.

Exploration of the neural correlates of cerebral palsy for sensorimotor BCI control

Cerebral palsy (CP) includes a broad range of disorders, which can result in impairment of posture and movement control. Brain-computer interfaces (BCIs) have been proposed as assistive devices for individuals with CP. Better understanding of the neural processing underlying motor control in affected individuals could lead to more targeted BCI rehabilitation and treatment options. We have explored well-known neural correlates of movement, including event-related desynchronization (ERD), phase synchrony, and a recently-introduced measure of phase dynamics, in participants with CP and healthy control participants. Although present, significantly less ERD and phase locking were found in the group with CP. Additionally, inter-group differences in phase dynamics were also significant. Taken together these findings suggest that users with CP exhibit lower levels of motor cortex activation during motor imagery, as reflected in lower levels of ongoing mu suppression and less functional connectivity. These differences indicate that development of BCIs for individuals with CP may pose additional challenges beyond those faced in providing BCIs to healthy individuals.

Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study

Background: Public health strategies to lower cardiovascular disease (CVD) risk involve reducing dietary saturated fatty acid (SFA) intake to ≤10% of total energy (%TE). However, the optimal type of replacement fat is unclear. Objective: We investigated the substitution of 9.5-9.6%TE dietary SFA with either monounsaturated (MUFA) or n-6 polyunsaturated fatty acids (PUFA) on vascular function and other CVD risk factors. Design: Using a randomized, controlled, single-blind, parallel group dietary intervention, 195 men and women aged 21-60 y with moderate CVD risk (≥50% above the population mean) from the United Kingdom followed one of three 16-wk isoenergetic diets (%TE target compositions, total fat:SFA:MUFA:n-6 PUFA): SFA-rich (36:17:11:4, n = 65), MUFA-rich (36:9:19:4, n = 64) or n-6 PUFA-rich (36:9:13:10, n = 66). The primary outcome measure was flow-mediated dilatation (%FMD); secondary outcome measures included fasting serum lipids, microvascular reactivity, arterial stiffness, ambulatory blood pressure, and markers of insulin resistance, inflammation and endothelial activation. Results: Replacing SFA with MUFA or n-6 PUFA did not significantly impact on %FMD (primary endpoint) or other measures of vascular reactivity. Of the secondary outcome measures, substitution of SFA with MUFA attenuated the increase in night systolic blood pressure (-4.9 mm Hg, P = 0.019) and reduced E-selectin (-7.8%, P = 0.012). Replacement with MUFA or n-6 PUFA lowered fasting serum total cholesterol (TC; -8.4% and -9.2%, respectively), low-density lipoprotein cholesterol (-11.3% and -13.6%) and TC to high-density lipoprotein cholesterol ratio (-5.6% and -8.5%) (P ≤ 0.001). These changes in low-density lipoprotein cholesterol equate to an estimated 17-20% reduction in CVD mortality. Conclusions: Substitution of 9.5-9.6%TE dietary SFA with either MUFA or n-6 PUFA did not impact significantly on %FMD or other measures of vascular function. However, the beneficial effects on serum lipid biomarkers, blood pressure and E-selectin offer a potential public health strategy for CVD risk reduction.

Chronic ouabain treatment exacerbates blood pressure elevation in spontaneously hypertensive rats: the role of vascular mechanisms

Objective Hypertensive rats are more sensitive to the pressor effects of acute ouabain than normotensive rats. We analyzed the effect of chronic ouabain (similar to 8.0 mu g/day, 5 weeks) treatment on the blood pressure of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats and the contribution of vascular mechanisms. Methods Responses to acetylcholine and phenylephrine were analyzed in isolated tail arteries. Protein expression of endothelial nitric oxide synthase and cyclooxygenase-2 (COX-2) were also investigated. Results Ouabain treatment enhanced blood pressure only in SHRs. The pD(2) for acetylcholine was decreased in arteries from SHRs compared with Wistar-Kyoto rats, and ouabain did not change this parameter. However, ouabain was able to increase the pD(2) to phenylephrine in SHRs. Nitric oxide synthase inhibition with N(G)-nitro-L-arginine methyl ester or potassium channel blockade by tetraetylamonium increased the response to phenylephrine in SHRs, with a smaller increase in response observed in ouabain-treated SHRs. In addition, indomethacin (a COX inhibitor) and ridogrel (a thromboxane A(2) synthase inhibitor and prostaglandin H(2)/thromboxane A(2) receptor antagonist) decreased contraction to phenylephrine in tail rings from ouabain-treated SHRs. Protein expression of endothelial nitric oxide synthase was unaltered following ouabain treatment in SHRs, whereas COX-2 expression was increased. Conclusion Chronic ouabain treatment further increases the raised blood pressure of SHRs. This appears to involve a vascular mechanism, related to a reduced vasodilator influence of nitric oxide and endothelium-derived hyperpolarizing factor and increased production of vasoconstrictor prostanoids by COX-2. These data suggest that the increased plasma levels of ouabain could play an important role in the maintenance of hypertension and the impairment of endothelial function. J Hypertens 27:1233-1242 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people

The polymorphisms of endothelial nitric oxide synthase (eNOS) are associated with reduced eNOS activity. Aerobic exercise training (AEX) may influence resting nitric oxide (NO) production, oxidative stress and blood pressure. The purpose of this study was to investigate the effect of AEX on the relationship among blood pressure, eNOS gene polymorphism and oxidative stress in pre-hypertensive older people. 118 pre-hypertensive subjects (59 +/- A 6 years) had blood samples collected after a 12 h overnight fast for assessing plasma NO metabolites (NOx) assays, thiobarbituric acid reactive substances (T-BARS) and superoxide dismutase activity (ecSOD). eNOS polymorphism (T-786C and G-894T) was done by standard PCR methods. All people were divided according to the genotype results (G1: TT/GG, G2: TT/GT + TT, G3: TC + CC/GG, G4: TC + CC/GT + TT). All parameters were measured before and after 6 months of AEX (70% of VO(2 max)). At baseline, no difference was found in systolic and diastolic blood pressure, ecSOD and T-BARS activity. Plasma NOx levels were significantly different between G1 (19 +/- A 1 mu M) and G4 (14.2 +/- A 0.6 mu M) and between G2 (20.1 +/- A 1.7 mu M) and G4 (14.2 +/- A 0.6 mu M). Therefore, reduced NOx concentration in G4 group occurred only when the polymorphisms were associated, suggesting that these results are more related to genetic factors than NO-scavenging effect. After AEX, the G4 increased NOx values (17.2 +/- A 1.2 mu M) and decreased blood pressure. G1, G3 and G4 decreased T-BARS levels. These results suggest the AEX can modulate the NOx concentration, eNOS activity and the relationship among eNOS gene polymorphism, oxidative stress and blood pressure especially in C (T-786C) and T (G-894T) allele carriers.

Evaluation of the Omron MX3 Plus monitor for blood pressure measurement in adolescents

This study analyzed the accuracy/agreement of the Omron MX3 monitor on 165 adolescents. Blood pressure was measured by the automatic monitor connected in Y with the mercury column (three consecutive and simultaneous measures). The independent measures were analyzed, and the mean differences between systolic and diastolic measures for both methods were calculated and compared with British Hypertension Society (BHS) and Association for the Advancement of Medical Instrumentation (AAMI) criteria. The automatic monitor received the highest degree of BHS recommendations for systolic and diastolic blood pressures according to the BHS. The median (25th and 75th) difference between the observer and the monitor measurements was -2 (-6 and 1) mmHg for systolic and 0 (-3 and1) mmHg for diastolic pressures. The monitor also satisfies the AAMI standard for the studied population. In conclusion, the Omron MX3 Plus monitor can be considered reliable and valid for clinical practice and is in accordance with BHS and AAMI criteria.

The Accuracy of National Body Fat Cutoff Levels in the Prediction of Elevated Blood Pressure among Brazilian Male Adolescents

Objective: To assess viability of the development of percentage body fat cutoffs based on blood pressure values in Brazilian adolescents.Methods: A cross-sectional study was conducted with a sample of 358 male subjects from 8 to 18 years old. Blood pressure was measured by the oscilometric method, and body composition was measured by dual-energy X-ray absorptiometry (DXA).Results: For the identification of elevated blood pressure, these nationally developed body fat cutoffs presented relative accuracy. The cutoffs were significantly associated with elevated blood pressure [odds ratio = 5.91 (95% confidence interval: 3.54-9.86)].Conclusions: Development of national body fat cutoffs is viable, because presence of high accuracy is an indication of elevated blood pressure.

Incidence of high blood pressure in a group of tannery workers in Brazil

O objetivo deste estudo foi medir a incidência de hipertensão arterial sistêmica em um curtume de médio porte em Botucatu, São Paulo, Sudeste do Brasil, onde havia sido observada, em estudo prévio, uma correlação positiva entre tempo de trabalho e níveis pressóricos, bem como uma alta prevalência de hipertensão. Para tanto, uma coorte de trabalhadores desse curtume foi acompanhada durante sete anos. Ao final do seguimento, estimou-se a taxa de incidência de hipertensão arterial como 0,0964.ano-1, valor considerado elevado se comparado com o encontrado em outros grupos profissionais.

Recovery of high blood pressure after chronic lesions of the commissural NTS in SHR

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nitric oxide of the supraoptic nucleus influences the salivary secretion, sodium renal excretion, urinary volume and arterial blood pressure induced by pilocarpine

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle and stainless steel cannulas were implanted into their supraoptic nucleus (SON). We investigated the effects of the injection into the supraoptic nucleus (SON) of FK 409, a nitric oxide donor, and N(W-)nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor (NOS), on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine, which was injected into SON. The drugs were injected in 0.5 mul volume over 30-60 s. Controls was injected with a similar volume of 0.15 M NaCl. FK 409 and L-NAME were injected at doses of 20 mug/0.5 mul and 40 mug/0.5 mul. respectively. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into SON. Injection of pilocarpine (10, 20, 40, 80, 160 mug/mul) into SON produced a dose-dependent increase in salivary secretion. L-NAME was injected into SON prior to the injection of pilocarpine into SON, producing an increase in salivary secretion due to the effect of pilocarpine. FK 409 injected into SON attenuating the increase in salivary secretion induced by pilocarpine. Mean arterial pressure (MAP) increase after injections of pilocarpine into the SON. L-NAME injected into the SON prior to injection of pilocarpine into SON increased the MAP. FK 409 injected into the SON prior to pilocarpine attenuated the effect of pilocarpine on MAP. Pilocarpine (0.5 mumol/0.5 mul) injected into the SON induced an increase in sodium and urinary excretion. L-NAME injected prior to pilocarpine into the SON increased the urinary sodium excretion and urinary volume induced by pilocarpine. FK 409 injected prior to pilocarpine into the SON decreased the sodium excretion and urinary volume induced by pilocarpine. All these roles of pilocarpine depend on the release of nitric oxide into the SON. In summary the present results show: a) SON is involved in pilocarpine-induced salivation; b) that mechanism involves increase in MAP, sodium excretion and urinary volume. (C) 2003 Elsevier B.V. All rights reserved.

Lateral hypothalamus lesions influences water and salt intake, and sodium and urine excretion, and arterial blood pressure induced by L-NAME and FK 409 injections into median preoptic nucleus in conscious rats

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125,0 mg and zolazepan chloridrate 125,0 mg) into quadriceps muscle and submitted an electrolytic lesion of the lateral hypothalamus (LH) and a stainless steel cannula was implanted into their median preoptic nucleus (MnPO). We investigated the effects of the injection into the (MnPO) of FK 409 (20 mug/0.5 mul), a nitric oxide (NO) donor, and N-W-nitro-L-arginine methyl ester (L-NAME) 40 mug/0.5 mul, a nitric oxide synthase inhibitor (NOSI), on the water and sodium appetite and the natriuretic, diuretic and cardiovascular effects induced by injection of L-NAME and FK 409 injected into MnPO in rats with LH lesions. Controls were injected with a similar volume of 0.15 M NaCl. L-NAME injected into MnPO produced an increase in water and sodium intake and in sodium and urine excretion and increase de mean arterial pressure (MAP). FK 409 injected into MnPO did not produce any change in the hydro electrolytic and cardiovascular parameters in LH-sham and lesioned rats. FK 409 injected before L-NAME attenuated its effects. These data show that electrolytic lesion of the LH reduces fluid and sodium intake as well as sodium and urine excretion, and the pressor effect induced by L-NAME. LH involvement with NO of the MnPO excitatory and inhibitory mechanisms related to water and sodium intake, sodium excretion and cardiovascular control is suggested. (C) 2004 Elsevier B.V. All rights reserved.

Vasopressin and angiotensin receptors of the medial septal area in the control of mean arterial pressure induced by vasopressin

Introduction. Brain arginine(8)-vasopressin (AVP), through the V-1a- and V-2-receptors, is essential for the maintenance of mean arterial pressure (MAP). Central AVP interacts with the components of the renin-angiotensin system, which participate in MAP regulation. This study all to determine the effects of V-1a-, V-2- and V-1a/V-2-AVP selective antagonists and AT(1)- and AT(2)-angiotensin II (Ang II) selective antagonists on the MAP induced by AVP injected into the medial septal area (MSA) of the brain.Materials and methods. Male Holtzman rats with stainless steel cannulae implanted into the MSA were used in experiments. Direct MAP was recorded in Conscious rats.Results. AVP administration into the MSA caused a prompt and potent pressor response in a dose-dependent fashion. Pretreatment with the V-1a- and V-2-antagonists reduced, whereas prior injection of the V-1a/V-2-antagonist induced a decrease in the MAP that remained below the baseline. Both AT(1)- and AT(2)-antagonists elicited a decrease, While simultaneous injections of two antagonists were more effective in decreasing the MAP induced AVP.Conclusion. These results indicate there is a synergism bell the V-1a- and V-2-AVP, and AT(1)- AT, and AT(2)-Ang II receptors in the MSA in the regulation of MAP.