Blood Pressure In Healthy Volunteers Research Articles

Wrist ballistocardiography and invasively recorded blood pressure in healthy volunteers during reclining bike exercise.

Objective: Ballistocardiogram (BCG) features are of interest in wearable cardiovascular monitoring of cardiac performance. We assess feasibility of wrist acceleration BCG during exercise for estimating pulse transit time (PTT), enabling broader cardiovascular response studies during acute exercise and improved monitoring in individuals at risk for cardiovascular disease (CVD). We also examine the relationship between PTT, blood pressure (BP), and stroke volume (SV) during exercise and posture interventions. Methods: 25 participants underwent a bike exercise protocol with four incremental workloads (0W, 50W, 100W, and 150W) in supine and semirecumbent postures. BCG, invasive radial artery BP, tonometry, photoplethysmography (PPG) and echocardiography were recorded. Ensemble averages of BCG signals determined aortic valve opening (AVO) timings, combined with peripheral pulse wave arrival times to calculate PTT. We tested for significance using Wilcoxon signed-rank test. Results: BCG was successfully recorded at the wrist during exercise. PTT exhibited a moderate negative correlation with systolic BP (ρSup = -0.65, ρSR = -0.57, ρAll = -0.54). PTT differences between supine and semirecumbent conditions were significant at 0W and 50W (p < 0.001), less at 100W (p = 0.0135) and 150W (p = 0.031). SBP and DBP were lower in semirecumbent posture (p < 0.01), while HR was slightly higher. Echocardiography confirmed association of BCG features with AVO and indicated a positive relationship between BCG amplitude and SV (ρ = 0.74). Significance: Wrist BCG may allow convenient PTT and possibly SV tracking during exercise, enabling studies of cardiovascular response to acute exercise and convenient monitoring of cardiovascular performance.

Effect of the Red Bull Energy Drink on Perfusion-Related Variables in Women Undergoing Microsurgical Breast Reconstruction: Protocol and Analysis Plan for a Prospective, Multicenter Randomized Controlled Trial

Maintaining a sufficiently high systolic blood pressure is essential for free flap perfusion after microsurgical breast reconstruction. Yet, many women undergoing these procedures have low postoperative systolic blood pressure. Intravenous volume administration or vasopressors may be needed to maintain systolic blood pressure above a predefined threshold. However, excessive volume administration may lead to volume overload and flap stasis, and the postoperative use of vasopressors may be limited depending on institutional standards. Additional nonpharmacological measures to raise blood pressure might be beneficial. Evidence suggests that the Red Bull energy drink could raise blood pressure. It has been shown to increase systolic and diastolic blood pressure in healthy volunteers and athletes. The primary objective of this study is to determine the difference in systolic blood pressure between an intervention group receiving Red Bull and a control group receiving still water after microsurgical breast reconstruction. Secondary objectives include postoperative heart rate, 24-hour fluid balance, pain level, or necessity for revision surgery due to flap complications. The Red Bull study is a prospective, multicenter randomized controlled trial comparing the effect of postoperative ingestion of Red Bull energy drink against still water in female patients undergoing unilateral microsurgical breast reconstruction. A total of 250 mL of Red Bull (intervention group) or 250 mL of still water (control group) will be administered to the study participants 2 hours postoperatively as well as for breakfast and lunch on postoperative day 1, amounting to a total volume of 750 mL per 24 hours. Female patients between 18 and 70 years of age undergoing unilateral microsurgical breast reconstruction will be included. Exclusion criteria are a history of arterial hypertension, cardiac rhythm disorder, diabetes mellitus, gastric or duodenal ulcer, thyroid disease, and current use of antihypertensive or antiarrhythmic drugs or thyroid hormones, as well as intolerance to Red Bull. Recruitment for the study started in June 2020 and was completed in December 2022. There is evidence that the Red Bull energy drink increases blood pressure in healthy volunteers and athletes. We hypothesize that postoperative ingestion of Red Bull will increase systolic blood pressure in women after microsurgical breast reconstruction. Red Bull could hence be used as a nonpharmacological adjunct to vasopressors or volume administration in women with hypotensive blood pressure after microsurgical breast reconstruction. This paper describes the Red Bull study trial protocol and analysis plan. The information will increase the transparency of the data analysis for the Red Bull study. ClinicalTrials.gov NCT04397419; https://clinicaltrials.gov/ct2/show/NCT04397419. DERR1-10.2196/38487.

Auricular Acupressure Effect on Autonomic Responses Evoked by a Cold Pressor Test in Healthy Volunteers: A Pilot Study.

This pilot study was conducted to investigate changes in the pulse rate and blood pressure in healthy volunteers after applying auricular acupressure at the "heart acupoint." A total of 120 healthy volunteers with hemodynamic indexes within normal limits were randomly allocated into 4 groups to receive auricular acupressure treatment either at the heart acupoint of the left or the right, or in both ears, and one control group without applying auricular acupressure. Before the application of auricular acupressure, there were no statistical differences in pulse rate and blood pressure increments among the four groups during the first cold pressor test. In groups in which auricular pressure was applied, the pulse rate was significantly reduced after the application of auricular acupressure in three groups; however, no statistically significant difference was detected among the groups. Changes in blood pressure were not statistically significant in or among the different groups after applying auricular acupressure. The average recorded pulse rate values during the second cold pressor test (after auricular acupressure) were significantly lower compared to the corresponding values taken during the first cold pressor test (before auricular acupressure) (p < 0.05); however, pulse rate increments during the two cold pressor tests (with and without auricular acupressure) were similar (p > 0.05). These findings suggest that auricular acupressure could be used as an adjunctive nonpharmacological method for reducing the pulse rate.

Study on Clinical Assessment of Central Blood Pressure in Healthy Volunteers, and its Relation to Clinical Phenotyping

The Unani system of Medicine is a holistic system of medicine and does not confine to molecular approach but refers to knowledge as a total recognition of the person and stresses on health of body, mind and soul. Unani medicine states that disease is a natural process and that symptoms are the reactions of the body to disease. The individual humoural balance is influenced by lifestyle factors. It employs the humoral theory which presupposes the presence of four akhlaat (humours) in the body – dam (blood), balgham (phlegm), safra (yellow bile) and sauda (black bile). The Unani philosophy has 4 humours under clinical phenotyping such as Sanguine (Damavi), Phlegmatic (Balghami), Bilious (Safravi) and Melancholic (Saudavi). The 400 Healthy volunteers with 100 each from four different temperaments (balghami, saudavi, safravi, damavi) were selected.The present study validates some of the Unani concepts of humours or temperament with central hemodynamic parameters or Pulse Wave Analysis (PWA). A specially designed case record form as per the Unani classical text was designed for assessment of humours and the information obtained were recorded from healthy volunteers as subjects and determination of central hemodynamic parameters was performed by SphygmoCor technology (AtCor Medical, Sydney, Australia). The temperament of the present study showed that the Pulse Wave Analysis in healthy volunteers although showed the results in physiological range but the analysis in safravi (bilious) subjects is found to be significant when compared to other clinical phenotypes.

PXR and 4β-Hydroxycholesterol Axis and the Components of Metabolic Syndrome.

Pregnane X receptor (PXR) activation has been found to regulate glucose and lipid metabolism and affect obesity in response to high-fat diets. PXR also modulates vascular tone. In fact, PXR appears to regulate multiple components of metabolic syndrome. In most cases, the effect of PXR action is harmful to metabolic health, and PXR can be hypothesized to play an important role in metabolic disruption elicited by exposure to endocrine-disrupting chemicals. The majority of the data on the effects of PXR activation on metabolic health come from animal and cell culture experiments. However, randomized, placebo-controlled, human trials indicate that the treatment with PXR ligands impairs glucose tolerance and increases 24-h blood pressure and heart rate. In addition, plasma 4β-hydroxycholesterol (4βHC), formed under the control of PXR in the liver, is associated with lower blood pressure in healthy volunteers. Furthermore, 4βHC regulates cholesterol transporters in peripheral tissues and may activate the beneficial reverse HDL cholesterol transport. In this review, we discuss the current knowledge on the role of PXR and the PXR–4βHC axis in the regulation of components of metabolic syndrome.

Effect of hot arm and foot bath on heart rate variability and blood pressure in healthy volunteers.

Background Though hot arm and foot bath (HAFB) is widely used, a precise physiological response is not reported. Hence, the present study was conducted to evaluate the effect of HAFB on heart rate variability (HRV) and blood pressure (BP) in healthy volunteers. Materials and Methods Sixteen healthy male volunteers' aged 23.81 ± 5.27 (mean ± standard deviation) years were recruited. All the subjects underwent only one session of HAFB (104-degree Fahrenheit) for the duration of 20 min. Assessments such as Electrocardiography and BP were taken before and after the intervention. Results Results of this study showed a significant reduction in systolic-BP (SBP), diastolic-BP (DBP), mean arterial pressure (MAP), the mean of the intervals between adjacent QRS complexes or the instantaneous heart rate (RR interval), the number of interval differences of successive NN intervals greater than 50ms (NN50), the proportion derived by dividing NN50 by the total number of NN intervals (pNN50), and high frequency (HF) band of HRV along with a significant increase in heart rate (HR), low-frequency (LF) band of HRV and LF/HF ratio compared to its baseline. Conclusions Results of this study suggest that 20 min of HAFB produce a significant increase in HR and a significant reduction in SBP, DBP, and MAP while producing parasympathetic withdrawal.

Effect of flunitrazepam as an oral hypnotic on 24-hour blood pressure in healthy volunteers.

The present study was carried out in order to assess the effects of chronic administration of flunitrazepam (as an oral hypnotic) on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. Following a 2-week placebo run-in period, 28 healthy volunteers (13 males and 15 females) between 21 and 30years were randomized to receive either flunitrazepam 1mg or placebo (both administered once a day in the evening) for 4weeks in two cross-over periods; each separated by a 2-week placebo period. At the end of each study period, non-invasive 24-h BP and HR ambulatory monitoring was performed. Flunitrazepam produced a significant decrease in nighttime systolic blood pressure (SBP) (- 6.4mmHg) and diastolic blood pressure (DBP) (- 4.1mmHg) (both P < 0.05 vs placebo) without affecting nocturnal HR. During the morning hours, significantly higher values of SBP (+ 7.4mmHg, P < 0.01), DBP (+ 3.4mmHg, P < 0.05) and HR (+ 3.9beats/min, P < 0.05) were observed in the flunitrazepam group compared to the placebo-treated group. No significant differences were noted between the two groups during afternoon and evening hours. These results suggest that chronic oral administration of 1mg flunitrazepam as a hypnotic agent causes a significant nocturnal fall in BP and a transient rebound increase of both BP and HR at awakening in the morning. Mechanisms underlying these cardiovascular effects remain unclear, although the direct vasodilatory effect, which is typical of flunitrazepam (with consequent reflex counter-regulatory responses), and the attenuation of baroreflex sensitivity are likely to play a major role.

A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study.

Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid used in multiple sclerosis and intractable epilepsies. Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. The aim of this study was to investigate if CBD reduces BP in humans. Nine healthy male volunteers were given 600 mg of CBD or placebo in a randomized, placebo-controlled, double-blind, crossover study. Cardiovascular parameters were monitored using a finometer and laser Doppler. CBD reduced resting systolic BP (-6 mmHg; P < 0.05) and stroke volume (-8 ml; P < 0.05), with increased heart rate (HR) and maintained cardiac output. Subjects who had taken CBD had lower BP (-5 mmHg; P < 0.05, especially before and after stress), increased HR (+10 bpm; P < 0.01), decreased stroke volume (-13 ml; P < 0.01), and a blunted forearm skin blood flow response to isometric exercise. In response to cold stress, subjects who had taken CBD had blunted BP (-6 mmHg; P < 0.01) and increased HR (+7 bpm; P < 0.05), with lower total peripheral resistance. This data shows that acute administration of CBD reduces resting BP and the BP increase to stress in humans, associated with increased HR. These hemodynamic changes should be considered for people taking CBD. Further research is required to establish whether CBD has a role in the treatment of cardiovascular disorders.

Immediate effect of cool spinal bath on blood pressure of healthy volunteers – Results of a single arm study

IntroductionHydrotherapy is the use of water in various forms for treating diseases. Traditionally, spinal baths have been a common hydrotherapy technique prescribed for treating high blood pressure. However, despite such traditional use there have been no documented studies conducted to scientifically evaluate this indication. This study is an attempt to examine traditional claims and possible mechanisms of spinal baths and their effect on blood pressure. Materials and methodsFifty healthy volunteers were randomly selected from medical students enrolled in a naturopathic programme. The participants were of both sexes aged between 18 and 25 years. A cool (26±1°C) spinal bath was given to each of the participants for 15min. The outcome measures were resting blood pressure, body temperature, pulse rate and breathing rate. Results47 participants completed the study (male 19%, female 81%), all the participants have shown significant reduction in blood pressure (p<.001), pulse rate (p<.001) and body temperature (p<.001) but breathing rate was not significant. DiscussionA cool spinal bath for 15min has shown a significant short-term reduction in both systolic and diastolic blood pressure, pulse rate and temperature which indicate that a cool spinal immersion may potentially have a role in managing hypertension. However, these observations are based on a short-term single arm pre-post design on normotensive students, and large scale randomised control trials over a longer period are needed to warrant better results.

Gastrointestinal absorption and metabolism of hesperetin-7-O-rutinoside and hesperetin-7-O-glucoside in healthy humans.

Hesperetin-7-O-rutinoside (hesperidin) reduces blood pressure in healthy volunteers but its intestinal absorption and metabolism are not fully understood. Therefore, we aimed to determine sites of absorption and metabolism of dietary flavanone glycosides in humans. Using a single-blind, randomized crossover design, we perfused equimolar amounts of hesperetin-7-O-rutinoside and hesperetin-7-O-glucoside directly into the proximal jejunum of healthy volunteers. We assessed the appearance of metabolites in the perfusate, blood and urine, to determine the sites of metabolism and excretion, and compared this to oral administration. The glucoside was rapidly hydrolyzed by brush border enzymes without any contribution from pancreatic, stomach, or other secreted enzymes, or from bacterial enzymes. Only ∼3% of the dose was recovered intact in the perfusate, indicating high absorption. A proportion was effluxed directly back into the perfused segment mainly in the form of hesperetin-3'-O-sulfate. In contrast, very little hydrolysis or absorption of hesperetin-7-O-rutinoside was observed with ∼80% recovered in the perfusate, no hesperetin metabolites were detected in blood and only traces were excreted in urine. The data elucidate the pathways of metabolism of dietary hesperidin in vivo and will facilitate better design of mechanistic studies both in vivo and in vitro.

Effects of a nitrate-rich meal on arterial stiffness and blood pressure in healthy volunteers

An increase in nitrate intake can augment circulating nitrite and nitric oxide. This may lead to lower blood pressure and improved vascular function. Green leafy vegetables, such as spinach, are rich sources of nitrate. We aimed to assess the acute effects of a nitrate-rich meal containing spinach on arterial stiffness and blood pressure in healthy men and women. Twenty-six participants aged 38–69years were recruited to a randomized controlled cross-over trial. The acute effects of two energy-matched (2000kJ) meals, administered in random order, were compared. The meals were either high nitrate (220mg of nitrate derived from spinach [spinach]) or low nitrate [control]. Outcome measurements were performed pre-meal and at specific time points up to 210min post meal. Spinach resulted in an eightfold increase in salivary nitrite and a sevenfold increase in salivary nitrate concentrations from pre-meal (P<0.001) to 120min post meal. Spinach compared with control resulted in higher large artery elasticity index (P<0.001), and lower pulse pressure (P<0.001) and systolic blood pressure (P<0.001). Post meal carotid–femoral pulse wave velocity (P=0.07), augmentation index (P=0.63), small artery elasticity index (P=0.98) and diastolic blood pressure (P=0.13) were not significantly altered by spinach relative to control. Therefore, consumption of a nitrate-rich meal can lower systolic blood pressure and pulse pressure and increase large artery compliance acutely in healthy men and women. If sustained, these effects could contribute to better cardiovascular health.

Enhanced Vasodilator Activity of Nitrite in Hypertension

Elevation of circulating nitrite (NO 2 − ) levels causes vasodilatation and lowers blood pressure in healthy volunteers. Whether these effects and the underpinning mechanisms persist in hypertension is unknown. Therefore, we investigated the consequences of systemic nitrite elevation in spontaneously hypertensive rats and conducted proof-of-principle studies in patients. Nitrite caused dose-dependent blood pressure–lowering that was profoundly enhanced in spontaneously hypertensive rats versus normotensive Wistar Kyoto controls. This effect was virtually abolished by the xanthine oxidoreductase (XOR) inhibitor, allopurinol, and associated with hypertension-specific XOR-dependent nitrite reductase activity localized to the erythrocyte but not the blood vessel wall. To determine whether these pathways translate to human hypertension, we investigated the effects of elevation of circulating nitrite levels in 15 drug naïve grade 1 hypertensives. To elevate nitrite, we used a dose of dietary nitrate (≈3.5 mmol) that elevated nitrite levels ≈1.5-fold ( P &lt;0.01); a rise shown previously to exert no significant blood pressure–lowering effects in normotensives. This dose caused substantial reductions in systolic (≈12 mm Hg) and diastolic blood pressures ( P &lt;0.001) and pulse wave velocity ( P &lt;0.05); effects associated with elevations in erythrocytic XOR expression and XOR-dependent nitrite reductase activity. Our observations demonstrate the improved efficacy of inorganic nitrate and nitrite in hypertension as a consequence of increased erythrocytic XOR nitrite reductase activity and support the concept of dietary nitrate supplementation as an effective, but simple and inexpensive, antihypertensive strategy.

Acute Effects of Chlorogenic Acid on Nitric Oxide Status, Endothelial Function, and Blood Pressure in Healthy Volunteers: A Randomized Trial

There is mounting evidence that specific dietary polyphenols can enhance vascular health by augmenting nitric oxide. Our aim was to investigate the acute effects of chlorogenic acid, an important dietary phenolic acid present in coffee (400 mg, equivalent to 2 cups of coffee), on nitric oxide status, endothelial function, and blood pressure. Healthy men and women (n = 23) were recruited to a randomized, double-blind, placebo-controlled, crossover trial. Chlorogenic acid resulted in significantly higher plasma concentrations of chlorogenic acid (P < 0.001). Relative to control, the mean post-treatment systolic blood pressure (-2.41 mmHg, 95% CI: -0.03, -4.78; P = 0.05) and diastolic blood pressure (-1.53 mmHg, 95% CI: -0.05, -3.01; P = 0.04) were significantly lower with chlorogenic acid. Markers of nitric oxide status (P > 0.10) and the measure of endothelial function (P = 0.60) were not significantly influenced. Chlorogenic acid can lower blood pressure acutely, an effect that, if sustained, would benefit cardiovascular health.

Acute effects of chlorogenic acid on nitric oxide status, endothelial function and blood pressure in healthy volunteers: A randomised trial

Acute effects of chlorogenic acid on nitric oxide status, endothelial function and blood pressure in healthy volunteers: A randomised trial

The effect of cryotherapy on oral mucosa: a study in healthy volunteers

Oral cryotherapy causes local vasoconstriction, which reduces blood flow and reduces the cytotoxic damage to the oral mucosa, has been shown to reduce oral mucositis after intense cytostatic treatment. The main object of this study was to investigate the effect of oral cryotherapy on the temperature in the oral mucosa, the level of proinflammatory cytokine interleukin-6 (IL-6) in saliva and the effect on blood pressure in healthy volunteers, before and after 1 h of cooling the oral cavity with crushed ice. Twelve healthy volunteers [mean age 32.4 (SD 13.2) (20-56) years] were treated with oral cryotherapy in the form of crushed ice. Temperature measurements were performed in the oral mucosa using infrared thermograph following a flowchart protocol. Blood pressure (BP) was measured with a sphygmomanometer. Saliva was analysed for inflammatory cytokine IL-6, using an enzyme-linked immunosorbent assay (ELISA). All participants fulfilled the cooling session. The temperature in the oral cavity decreased significantly (mean 12.9 °C, p < .002). The systolic BP was marginally but significantly higher after cooling (~5 mmHg, p = .019). We could not detect any differences in cytokine IL-6 levels before and after oral cooling. We conclude that cryotherapy during 1 h lowers the mucosal temperature as much as ~12.9 °C, which explains the significant protective effect against mucosal damage by cytostatic drugs. The cooling caused no increase in IL-6 levels. Systemic blood pressure was marginally increased.

Hyperthermia by bathing in a hot spring improves cardiovascular functions and reduces the production of inflammatory cytokines in patients with chronic heart failure

Balneotherapy has been shown to reduce systemic blood pressure in healthy volunteers. Hyperthermia might ameliorate the inflammatory status in heart failure through improving cardiac function. The purpose of this study was to examine the beneficial effects of balneotherapy in patients with chronic heart failure (CHF). Thirty-two patients with systolic CHF classified as New York Heart Association functional status II or III were randomized to divide either a balneotherapy group or a control group. The patients in the balneotherapy group were immersed in a hot spring at 40°C for 10 min daily for 2 weeks; the control group patients took a shower daily. The left ventricular ejection fraction (EF) and cardiothoracic ratio (CTR) were evaluated and plasma brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were measured. The clinical symptoms improved after 2 weeks of hot spring therapy. Although the heart rate did not change, clinical symptoms, CTR, EF, and BNP were significantly improved. Moreover, the inflammatory responses, including hsCRP, TNF-α and IL-6 decreased significantly after balneotherapy. The improvement of BNP correlates with the changes in inflammatory biomarkers. Repeated hyperthermia by bathing in a hot spring is therefore considered to improve the cardiac and inflammatory status in patients with CHF.

Reply to Lundberg, Larsen, and Weitzberg

to the editor: The letter of Lundberg et al. ([12][1]) does not relate directly to any of the articles we published in this journal ([1][2], [2][3], [6][4]). Rather, the correspondents make a general point on the potential risks to athletes who might choose to supplement their diet with nitrate or (

P51. Interruption of the entero-salivary metabolism of nitrate to nitrite increases blood pressure in healthy volunteers

P51. Interruption of the entero-salivary metabolism of nitrate to nitrite increases blood pressure in healthy volunteers

The effect of conjugated linoleic acid, a natural trans fat from milk and meat, on human blood pressure: results from a randomized crossover feeding study

Cis-9, trans-11 conjugated linoleic acid (CLA) is a natural trans fatty acid that is largely restricted to ruminant fats and consumed in foods and supplements. Its role in blood pressure (BP) regulation is still unclear. We examined the effect of cis-9, trans-11 CLA on BP compared with oleic acid. A total of 61 healthy volunteers were sequentially fed each of 3 diets for 3 weeks, in random order, for a total of 9 weeks. The diets were identical except for 7% of energy (18.9 g in a diet of 10 MJ day(-1)) that was provided either by oleic acid, by industrial trans fatty acids or by cis-9, trans-11 CLA. We measured BP on two separate days at the end of each intervention period. At baseline, mean BP was 113.8±14.4 mm Hg systolic and 66.3±9.6 mm Hg diastolic. The effect of the CLA diet compared with the oleic acid diet was 0.11 mm Hg (95% confidence interval: -1.27, 1.49) systolic and -0.45 mm Hg (-1.63, 0.73) diastolic. After the industrial trans fatty acid diet, the effect was 1.13 mm Hg (-0.25, 2.51) systolic and -0.44 mm Hg (-1.62, 0.73) diastolic compared with the oleic acid diet. Our study suggests that short-term high intakes of cis-9,trans-11 CLA do not affect BP in healthy volunteers.

Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans

Ingestion of dietary (inorganic) nitrate elevates circulating and tissue levels of nitrite via bioconversion in the entero-salivary circulation. In addition, nitrite is a potent vasodilator in humans, an effect thought to underlie the blood pressure-lowering effects of dietary nitrate (in the form of beetroot juice) ingestion. Whether inorganic nitrate underlies these effects and whether the effects of either naturally occurring dietary nitrate or inorganic nitrate supplementation are dose dependent remain uncertain. Using a randomized crossover study design, we show that nitrate supplementation (KNO(3) capsules: 4 versus 12 mmol [n=6] or 24 mmol of KNO(3) (1488 mg of nitrate) versus 24 mmol of KCl [n=20]) or vegetable intake (250 mL of beetroot juice [5.5 mmol nitrate] versus 250 mL of water [n=9]) causes dose-dependent elevation in plasma nitrite concentration and elevation of cGMP concentration with a consequent decrease in blood pressure in healthy volunteers. In addition, post hoc analysis demonstrates a sex difference in sensitivity to nitrate supplementation dependent on resting baseline blood pressure and plasma nitrite concentration, whereby blood pressure is decreased in male volunteers, with higher baseline blood pressure and lower plasma nitrite concentration but not in female volunteers. Our findings demonstrate dose-dependent decreases in blood pressure and vasoprotection after inorganic nitrate ingestion in the form of either supplementation or by dietary elevation. In addition, our post hoc analyses intimate sex differences in nitrate processing involving the entero-salivary circulation that are likely to be major contributing factors to the lower blood pressures and the vasoprotective phenotype of premenopausal women.