Pressure In Humans Research Articles

Neuronal nitric oxide synthase contributes to the normalization of blood pressure in medicated hypertensive patients

Neuronal nitric oxide synthase (nNOS) is expressed in the cardiovascular system and besides NO, generates H2O2. nNOS has been proposed to contribute to the control of blood pressure in healthy humans. The aim of this study was to verify the hypothesis that nNOS can contribute to the control of vascular relaxation and blood pressure in hypertensive patients undergoing drug treatment. The study was conducted in resistance mesenteric arteries from 63 individuals, as follows: 1) normotensive patients; 2) controlled hypertensive patients (patients on antihypertensive treatment with blood pressure normalized); 3) uncontrolled hypertensive patients (patients on antihypertensive treatment that remained hypertensive). Only mesenteric arteries from uncontrolled hypertensive patients showed impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh). Selective nNOS blockade with inhibitor 1 and catalase, which decomposes H2O2, decreased vasorelaxation in the three groups. However, the inhibitory effect was greater in controlled hypertensive patients. Decreased eNOS expression was detected in both uncontrolled and controlled hypertensive groups. Interestingly nNOS expression and ACh-stimulated H2O2 production were greater in controlled hypertensive patients, than in the other groups. ACh-stimulated NO production was lower in controlled hypertensive when compared to normotensive patients, while uncontrolled hypertensive patients showed the lowest levels. Catalase and nNOS blockade inhibited ACh-induced H2O2 production. In conclusion, nNOS-derived H2O2 contributes to the endothelium-dependent vascular relaxation in human resistance mesenteric arteries. The endothelial dysfunction observed in uncontrolled hypertensive patients involves decreased eNOS expression and NO production. The normalization of vascular relaxation and blood pressure in controlled hypertensive patients involves increased nNOS-derived H2O2 and NO production.

Trans and Cis Conformations of the Antihypertensive Drug Valsartan Respectively Lock the Inactive and Active-like States of Angiotensin II Type 1 Receptor: A Molecular Dynamics Study.

Angiotensin II type 1 receptor (AT1R) is the principal regulator of blood pressure in humans. The overactivation of AT1R by the stimulation of angiotensin II would result in high blood pressure. To prevent hypertension, nonpeptide "sartan" drugs, such as valsartan (VST), have been developed to competitively block the access of angiotensin II to the receptor. Nuclear magnetic resonance spectroscopy and molecular modeling studies have identified that VST in solution and in lipid micelles (a mimic membrane environment) has two distinct trans/cis conformations (VSTtrans/VSTcis) that can be transformed into each other through the isomerization of the amide bond. To date, it is still not known whether the two conformations of VST can affect the binding of AT1R with VST. To this end, the binding of AT1R with VSTtrans or VSTcis was modeled based on the recently determined crystal structures of AT1R. Molecular dynamics simulations were then performed to study the structural and dynamical differences of AT1R caused by the two conformations of VST. Simulation results show that AT1R with VSTtrans has higher structural and dynamical stabilities compared to that with VSTcis. Binding energy analysis indicates that AT1R bind more strongly with VSTtrans, and the energy difference mainly results from the contribution of van der Waals and nonpolar interactions. Detailed analyses reveal that unlike AT1R with VSTtrans, AT1R with VSTcis displays an activate-like state, which is characterized by a small outward movement of transmembrane helix 6. Due to the altered interaction with the butyl group of VST, residue Tyr87 undergoes a conformational change that causes a contraction of the pocket for VST binding. The rearrangement of AT1R is then propagated to the intracellular side of the receptor through the conformational change of residue Trp253 (the toggle switch), which results in an expansion of the pocket for G protein binding and the breakage of the hydrogen bond containing the conserved residue Arg126. These data provide insights into the activation mechanism of AT1R caused by the binding of VSTcis, which may help to design a new drug to inhibit AT1R and prevent high blood pressure.

Abstract P289: Effect of Abaptacept on Blood Pressure in Essential Hypertensive Subjects with Rheumatological Disorders

We previously showed that abatacept, an inhibitor of T cell co-stimulation, prevents and reverses experimental hypertension. We now investigated whether it lowers blood pressure (BP) in humans. Of 1624 subjects receiving this drug in our de-identified electronic health record, 320 had hypertension and adequate baseline and follow up data (1 month to 3 years). Use of glucocorticoids (GC), non-steroidal antiinflammatory agents (NSAIDs), and antihypertensive drugs (HTND) was scored with the WHO system. ΔBPs at 1, 3 and 6 months and 1, 2 and 3 years after abatacept were adjusted for concomitant changes in medications and weights (Wt) by multivariate regression. Subjects were 80.6% female, 88.4% white, age 62±1 y, BMI 30.9±0.4 Kg/m 2 and BP 128.2±0.8/74.6±0.5 mmHg. Significant changes in confounders over time included decreases in GC, NSAID and HTND over the initial months followed by rebound beyond baseline at 2 and 3 years, and increases in Wt in these late periods. Changes in adjusted BP were limited to an increase in systolic BP at 2 years (1.75±1.04, p<0.05) and a decrease in diastolic BP at 3 years (-1.67±0.80, p<0.02). 91 subjects (28.4%) had a decrease of MAP ≥5 mmHg in at least half of the periods. ΔBP in these “responders” vs all other subjects was -10.8±0.7/-7.6±0.4, MAP -8.6±0.4 vs +5.0±0.4/+2.3±0.2, MAP +3.2±0.2, but these groups did not differ in sex, age, race, obesity, use of concomitant immunomodulators, pressors or blockers of the renin-angiotensin system (RASB). However, pooled adjusted ΔBP differed between women and men (diastolic -0.72±0.26 vs +1.48±0.48, p=0.0002; MAP -0.29±0.26 vs +1.58±0.55, p=0.003); between subjects younger and older than 65 y (systolic -0.05±0.48 vs +1.88±0.58, p=0.021; MAP -0.39±0.33 vs +0.64±0.37, p=0.037); and between those with BMI≤25 and >25 Kg/m 2 (systolic -1.31±0.79 vs +1.37±0.42, p<0.008). Finally, Δsystolic BP was -0.15±0.53 in subjects not taking and +1.42±0.50 in those taking RASB, p=0.037. In summary, long term use of abatacept mildly reduces BP in lean women with essential hypertension and rheumatological disorders. The effect is attenuated by obesity and perhaps also by aging and treatment with RASB. Further studies of abatacept in resistant essential hypertension are warranted, particularly in women.

Abstract 094: Smooth Muscle PPARγ Mutation Causes Impaired Renal Blood Flow and Salt-Sensitive Hypertension

Mutations in PPARγ cause hypertension (HT) while PPARγ activation lowers blood pressure (BP) in humans. To determine if vascular smooth muscle (VSM) PPARγ regulates salt sensitivity, we studied transgenic mice selectively expressing a HT-causing PPARγ mutant in VSM (S-P467L) and non-transgenic littermates (NT) fed a 4% high salt (HS) diet for 4 weeks. Salt equally suppressed plasma renin in both strains, but S-P467L mice exhibited increased systolic BP (S-P467L 136±3 mmHg vs NT 124±2 mmHg, p<0.01) and pulse wave velocity (3.1±0.1 vs 2.7±0.1 m/s, p<0.01) in response to HS. The salt-induced HT was not associated with changes in diastolic BP, sympathetic nerve activity, heart rate, or cardiac output. Thus, the pressor effect of HS was likely due to higher peripheral vascular resistance. HS-fed S-P467L mice developed impaired acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation in carotid (Max ACh relaxation: 31±4.9% vs 90±1.8%, p<0.01; Max SNP relaxation: 38±2.8% vs 89±2.6%, p<0.01) and basilar artery (Max ACh relaxation: -3.2±9.3% vs 57±5.9%, p<0.01). The impaired vasodilation rapidly developed after 3-day HS diet, preceding salt-induced BP elevation. Pre-incubation with a cyclooxygenase inhibitor indomethacin normalized ACh/SNP relaxation responses, and preliminary mass spectrometry indicated HS increased prostaglandin E2 in S-P467L aortas. HS-fed S-P467L mice had smaller renal artery luminal diameter (322±21 vs 389±22 μm, p<0.05) and blunted renal blood flow (36±3.6 vs. 50±6.4 μL/min/g, p<0.05). During the 4 th week of HS diet, S-P467L mice produced 31% less nitrate/nitrite in 24 hour urine compared to NT controls (2.2±0.3 vs 3.2±0.4 μmol, p<0.05), suggesting blunted renal bioavailability of nitric oxide, a potent inhibitor of Na-K-2Cl cotransporter (NKCC2). This was associated with a declined capacity of HS-fed S-P467L mice to excrete an acute volume/Na + load, which was rescued by an NKCC2 inhibitor furosemide, but not by the Na-Cl-cotransporter inhibitor hydrochlorothiazide. Our data support the novel concept that smooth muscle PPARγ regulates systemic vascular resistance, renal perfusion and tubular sodium transport, and loss of these protective actions of PPARγ predisposes to salt sensitivity and hypertension.

A multiscale model for the simulation of cerebral and extracerebral blood flows and pressures in humans.

Brain hemodynamics is fundamental for the functioning of the human being. Many biophysical factors affect brain circulation, so that a satisfactory understanding of its behavior is challenging. We developed a mathematical model to simulate cerebral and extracerebral flows and pressures in humans. The model is composed of an anatomically informed 1-D arterial network, and two 0-D networks of the cerebral circulation and brain drainage, respectively. It takes into account the pulse-wave transmission properties of the 55 main arteries and the main hydraulic and autoregulation mechanisms ensuring blood supply and drainage to the brain. Proper pressure outputs from the arterial 1-D model are used as input to the 0-D models, together with the contribution to venous pressure due to breathing that simulates the drainage effect of the thoracic pump. The model we developed is able to link the arterial tree with the venous pathways devoted to the brain drainage, and to simulate important factors affecting cerebral circulation both for physiological and pathological conditions, such as breathing and hypo/hypercapnia. Finally, the average value of simulated flows and pressures is in agreement with the available experimental data. The model has the potential to predict important clinical parameters before and after physiological and/or pathological changes.

Gastric cooling and menthol cause an increase in cardiac parasympathetic efferent activity in healthy adult human volunteers

What is the central question of this study? How do gastric stretch and gastric cooling stimuli affect cardiac autonomic control? What is the main finding and its importance? Gastric stretch causes an increase in cardiac sympathetic activity. Stretch combined with cold stimulation result in an elimination of the sympathetic response to stretch and an increase in cardiac parasympathetic activity, in turn resulting in a reduction in heart rate. Gastric cold stimulation causes a shift in sympathovagal balance towards parasympathetic dominance. The cold-induced bradycardia has the potential to decrease cardiac workload, which might be significant in individuals with cardiovascular pathologies. Gastric distension increases blood pressure and heart rate in young, healthy humans, but little is known about the effect of gastric stretch combined with cooling. We used a randomized crossover study to assess the cardiovascular responses to drinking 300ml of ispaghula husk solution at either 6 or 37°C in nine healthy humans (age 24.08±9.36years) to establish the effect of gastric stretch with and without cooling. The effect of consuming peppermint oil capsules to activate cold thermoreceptors was also investigated. The ECG, respiratory movements and continuous blood pressure were recorded during a 5min baseline period, followed by a 115min post-drink period, during which 5min epochs of data were recorded. Cardiac autonomic activity was assessed using time and frequency domain analyses of respiratory sinus arrhythmia to quantify parasympathetic autonomic activity, and corrected QT (QTc) interval analysis to quantify sympathetic autonomic activity. Gastric stretch only caused a significant reduction in QTc interval lasting up to 15min, with a concomitant but non-significant increase in heart rate, indicating an increased sympathetic cardiac tone. The additional effect of gastric cold stimulation was significantly to reduce heart rate for up to 15min, elevate indicators of cardiac parasympathetic tone and eliminate the reduction in QTc interval seen with gastric stretch only. Stimulation of gastric cold thermoreceptors with menthol also caused a significant reduction in heart rate and concomitant increase in the root mean square of successive differences. These findings indicate that gastric cold stimulation causes a shift in the sympathovagal balance of cardiac control towards a more parasympathetic dominant pattern.

Effects of Alfuzosin, an α1-Adrenergic Antagonist, on Anal Pressures and Bowel Habits in Women With and Without Defecatory Disorders

Some patients with defecatory disorders (DD) have high anal pressures that may impede rectal evacuation. Alpha-1 adrenoreceptors mediate as much as 50% of anal resting pressure in humans. We performed a randomized, placebo-controlled study of the effects of alfuzosin, an alpha1-adrenergic receptor antagonist, on anal pressures alone in healthy women and also on bowel symptoms in women with DD. In a double-blind study performed from March 2013 through March 2017, anal pressures were evaluated before and after 36 women with DD (constipation for at least 1 year) and 36 healthy women (controls) were randomly assigned (1:1) to groups given oral alfuzosin (2.5 mg immediate release) or placebo. Thereafter, patients were randomly assigned (1:1) to groups given oral alfuzosin (10 mg extended release) or placebo each day for 2 weeks. Participants kept daily diaries of bowel symptoms for 2 weeks before (baseline) and during administration of the test articles (treatment). Weekly questionnaires recorded the overall severity of constipation symptoms, bloating, abdominal pain, nausea, and vomiting; overall satisfaction with treatment of constipation was evaluated at weeks 2 and 4. The primary endpoint was the change in the number of spontaneous (SBMs) and complete SBMs (CSBMs) between the treatment and baseline periods. We evaluated relationships between stool form, passage, and complete evacuation. Alfuzosin reduced anal resting pressure by 32 ± 3 mm Hg versus 16 ± 3 mm Hg for placebo (P=.0001) and anal pressure during evacuation by 26 ± 3 mm Hg versus 16 ± 3 mm Hg for placebo, (P= .03). However, alfuzosin did not significantly increase the rectoanal gradient, SBMs or CSBMs compared with placebo. Both formulations of alfuzosin were well tolerated. Hard stools and the ease of passage during defecation accounted for 72% and 76% of the variance in the satisfaction after defecation, respectively, during baseline and treatment periods. In a randomized trial, alfuzosin reduced anal pressure at rest and during simulated evacuation in healthy and constipated women, compared with placebo, but did not improve bowel symptoms in constipated women. This could be because the drug does not improve stool form or dyssynergia, which also contribute to DD. ClinicalTrials.gov number, NCT01834729.

Two flavonoid metabolites, 3,4-dihydroxyphenylacetic acid and 4-methylcatechol, relax arteries ex vivo and decrease blood pressure in vivo

ScopeThe flavonoid quercetin reduces arterial blood pressure in animals and humans but the mechanisms remains elusive. The aim of this study was to test the activity of flavonoid microbial metabolites, which can participate on the final vasorelaxant effect. Methods and resultsBoth ex vivo (isolated rat thoracic aorta and mesenteric artery) and in vivo (normotensive and spontaneously hypertensive rats) approaches were used in this study.4-methylcatechol and 3,4-dihydroxyphenylacetic acid (DHPA) had greater vasorelaxant effects on mesenteric artery than 3-(3-hydroxyphenyl)propionic acid, the previously reported metabolite with vasorelaxant effect. In vivo testing confirmed their blood pressure decreasing effect given both as bolus and slow infusion. Their mechanism at molecular level was different. ConclusionsThis study is the first to show that flavonoid metabolites DHPA and 4-methylcatechol decrease arterial blood pressure and hence a mixture of microbial metabolites formed in the gastrointestinal tract may be responsible for or contribute to the effect of orally ingested quercetin.

The Effects of Oral Taurine on Resting Blood Pressure in Humans: a Meta-Analysis.

The aims of this meta-analysis were to investigate the effects of orally administered isolated taurine on resting systolic blood pressure (SBP) and diastolic blood pressure (DBP) in humans. There is growing evidence that taurine deficiency is associated with hypertension and that oral supplementation can have antihypertensive effects in humans. However, these investigations have been conducted across a number of decades and populations and have not been collectively reviewed. A search was performed using various databases in May 2018 and later screened using search criteria for eligibility. There were seven peer-reviewed studies meeting the inclusion criteria, encompassing 103 participants of varying age and health statuses. Taurine ingestion reduced SBP (Hedges' g = - 0.70, 95% CI - 0.98 to - 0.41, P < 0.0001) and DBP (Hedges' g = - 0.62, 95% CI - 0.91 to - 0.34, P < 0.0001). These results translated to mean ~ 3mmHg reductions in both SBP (range = 0-15mmHg) and DBP (range = 0-7mmHg) following a range of doses (1 to 6g/day) and supplementation periods (1day to 12weeks), with no adverse events reported. These preliminary findings suggest that ingestion of taurine at the stated doses and supplementation periods can reduce blood pressure to a clinically relevant magnitude, without any adverse side effects. Future studies are needed to establish the effects of oral taurine supplementation on targeted pathologies and the optimal supplementation doses and periods.

Reconstruction of continuous brachial artery pressure wave from continuous finger arterial pressure in humans.

Generalized transfer functions (GTFs) are available to compute the more relevant proximal blood pressure (BP) waveform from a more easily measured peripheral BP waveform. However, GTFs are based on the black box model. This paper presents a practical approach to reconstruct brachial artery pressure (BAP) distally from finger artery pressure (FAP). We assume that continuous BAP can be simply approximated by summing two halves of the continuous FAP shifted by the time delay. We firstly showed that the pressure wave in the finger artery can be considered twice as much as the forward/backward wave in the finger. A simplified individualized transfer function was then derived so as to estimate BAP from FAP. The effectiveness of the method was examined by experiment involving 26 healthy volunteers (26.7 ± 3.8years old) in a resting state. By comparing with a reference BAP, we found that the proposed method can correct the FAP. The errors of the proposed method in estimating systolic and diastolic pressures are - 0.6 ± 6.0 and - 0.6 ± 3.7mmHg, respectively. These results agree with the standard of Association for the Advancement of Medical Instrumentation (AAMI). We also found that the reconstructed BAP from FAP by terminal arterial occlusion technology (TAOT) is comparable to that of the artery occlusion technology (AOT). Our method or TAOT is promising in estimating continuous proximal blood pressure from peripheral blood pressure in practice.

Adaptive Landscape of Protein Variation in Human Exomes.

The human genome contains hundreds of thousands of missense mutations. However, only a handful of these variants are known to be adaptive, which implies that adaptation through protein sequence change is an extremely rare phenomenon in human evolution. Alternatively, existing methods may lack the power to pinpoint adaptive variation. We have developed and applied an Evolutionary Probability Approach (EPA) to discover candidate adaptive polymorphisms (CAPs) through the discordance between allelic evolutionary probabilities and their observed frequencies in human populations. EPA reveals thousands of missense CAPs, which suggest that a large number of previously optimal alleles experienced a reversal of fortune in the human lineage. We explored nonadaptive mechanisms to explain CAPs, including the effects of demography, mutation rate variability, and negative and positive selective pressures in modern humans. Many nonadaptive hypotheses were tested, but failed to explain the data, which suggests that a large proportion of CAP alleles have increased in frequency due to beneficial selection. This suggestion is supported by the fact that a vast majority of adaptive missense variants discovered previously in humans are CAPs, and hundreds of CAP alleles are protective in genotype–phenotype association data. Our integrated phylogenomic and population genetic EPA approach predicts the existence of thousands of nonneutral candidate variants in the human proteome. We expect this collection to be enriched in beneficial variation. The EPA approach can be applied to discover candidate adaptive variation in any protein, population, or species for which allele frequency data and reliable multispecies alignments are available.

Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans

Imbalances in the oral microbial community have been associated with reduced cardiovascular and metabolic health. A possible mechanism linking the oral microbiota to health is the nitrate (NO3-)-nitrite (NO2-)-nitric oxide (NO) pathway, which relies on oral bacteria to reduce NO3- to NO2-. NO (generated from both NO2- and L-arginine) regulates vascular endothelial function and therefore blood pressure (BP). By sequencing bacterial 16S rRNA genes we examined the relationships between the oral microbiome and physiological indices of NO bioavailability and possible changes in these variables following 10 days of NO3- (12 mmol/d) and placebo supplementation in young (18–22 yrs) and old (70–79 yrs) normotensive humans (n = 18). NO3- supplementation altered the salivary microbiome compared to placebo by increasing the relative abundance of Proteobacteria (+225%) and decreasing the relative abundance of Bacteroidetes (−46%; P < 0.05). After NO3-supplementation the relative abundances of Rothia (+127%) and Neisseria (+351%) were greater, and Prevotella (−60%) and Veillonella (−65%) were lower than in the placebo condition (all P < 0.05). NO3- supplementation increased plasma concentration of NO2- and reduced systemic blood pressure in old (70–79 yrs), but not young (18–22 yrs), participants. High abundances of Rothia and Neisseria and low abundances of Prevotella and Veillonella were correlated with greater increases in plasma [NO2-] in response to NO3- supplementation. The current findings indicate that the oral microbiome is malleable to change with increased dietary intake of inorganic NO3-, and that diet-induced changes in the oral microbial community are related to indices of NO homeostasis and vascular health in vivo.

Effects of Topical Latanoprost on Intraocular Pressure and Myopia Progression in Young Guinea Pigs.

PurposeTo determine whether latanoprost, a prostaglandin analog proven to be very effective in reducing intraocular pressure (IOP) in humans, can also slow myopia progression in the guinea pig form deprivation (FD) model.MethodsTwo-week-old pigmented guinea pigs underwent monocular FD and daily topical latanoprost (0.005%, n = 10) or artificial tears (control, n = 10) starting 1 week after the initiation of FD, with all treatments continuing for a further 9 weeks. Tonometry, retinoscopy, and high-frequency A-scan ultrasonography were used to monitor IOP, refractive error, and ocular axial dimensions, respectively.ResultsLatanoprost significantly reduced IOP and slowed myopia progression. Mean interocular IOP differences (±SEM) recorded at baseline and week 10 were −0.30 ± 0.51 and 1.80 ± 1.16 mm Hg (P = 0.525) for the control group and 0.07 ± 0.35 and −5.17 ± 0.96 mm Hg (P < 0.001) for the latanoprost group. Equivalent interocular differences for optical axial length at baseline and week 10 were 0.00 ± 0.015 and 0.29 ± 0.04 mm (P < 0.001; control) and 0.02 ± 0.02 and 0.06 ± 0.02 mm (P = 0.202; latanoprost), and for refractive error were +0.025 ± 0.36 and −8.2 ± 0.71 diopter (D) (P < 0.001; control), and −0.15 ± 0.35 and −2.25 ± 0.54 D (P = 0.03; latanoprost).ConclusionsIn the FD guinea pig model, latanoprost significantly reduces the development of myopia. Although further investigations into underlying mechanisms are needed, the results open the exciting possibility of a new line of myopia control therapy.

The orphan G protein-coupled receptor 25 (GPR25) is activated by Apelin and Apela in non-mammalian vertebrates

G protein-coupled receptor 25 (GPR25) is an orphan G protein-coupled receptor in vertebrates, that has been implicated to be associated with autoimmune diseases and regulate blood pressure in humans. However, the endogenous ligand of GPR25 remains unknown in vertebrates. Here, we reported that in non-mammalian vertebrates (zebrafish, spotted gars, and pigeons), GPR25 could be activated by Apelin and Apela peptides, which are also the two endogenous ligands of vertebrate Apelin receptor (APLNR). Using the pGL3-CRE-luciferase reporter assay and confocal microscopy, we first demonstrated that like APLNR, zebrafish GPR25 expressing in HEK293 cells could be effectively activated by zebrafish Apelin and Apela peptides, leading to the inhibition of forskolin-stimulated cAMP production and receptor internalization. Like zebrafish GPR25, pigeon and spotted gar GPR25 could also be activated by Apelin and Apela, and their activation could inhibit forskolin-induced cAMP accumulation. Interestingly, unlike zebrafish (/spotted gar/pigeon) GPR25, human GPR25 could not be activated by Apelin and Apela under the same experimental conditions. RNA-seq analysis further revealed that GPR25 is expressed in a variety of tissues, including the testes and intestine of zebrafish/spotted gars/humans, implying the potential roles of GPR25 signaling in many physiological processes in vertebrates. Taken together, our data not only provides the first proof that the orphan receptor GPR25 possesses two potential ligands ‘Apelin and Apela’ and its activation decreases intracellular cAMP levels in non-mammalian vertebrates, but also facilitates to unravel the physiological roles of GPR25 signaling in vertebrates.

Effects of fragrance inhalation of essential oil on control of blood pressure and muscle sympathetic nerve activity in humans

AimsWe recently reported that inhalation of fragrance of Grapefruit essential oil increased blood pressure (BP) while that of Marjoram essential oil decreased BP in humans. In this study, we investigated the effects of fragrance inhalation of Grapefruit and Marjoram essential oil on control of BP and muscle sympathetic nerve activity (MSNA), and also cardiovagal and sympathetic baroreflex function.MethodsThirteen healthy subjects participated in each trial of this study. The experiment was performed in the supine position. Subjects breathed blank air through a face mask for 10 min as baseline. Then, they inhaled air with the fragrance of Grapefruit or Marjoram essential oil from Douglas bags for 10 min. Throughout the trial, MSNA (peroneal nerve, microneurography), beat‐by‐beat heart rate and BP, and breath‐by‐breath respiratory variables were recorded continuously.ResultsBy inhalation of the fragrance of Grapefruit essential oil, diastolic BP increased at 8 to 10 min of inhalation (64 ± 9 mmHg) compared to baseline (62 ± 9 mmHg), whereas MSNA burst rate remained unchanged at the period of inhalation (14.2 ± 8.5 bursts/min) from baseline (13.2 ± 7.0 bursts/min). Cardiovagal (10.8 ± 5.6 vs. 11.9 ± 9.6 ms/mmHg) or sympathetic baroreflex sensitivity (−0.84 ± 0.61 vs. −1.03 ± 0.78 au/mmHg) remained unchanged from baseline at the period of inhalation. On the other hand, by inhalation of the fragrance of Marjoram essential oil, diastolic BP increased at 8 to 10 min of inhalation (61 ± 7 mmHg) compared to baseline (60 ± 8 mmHg) against our previous studies, while MSNA burst rate remained unchanged at the period of inhalation (14.0 ± 8.5 bursts/min) from baseline (12.0 ± 9.4 bursts/min). Cardiovagal (12.0 ± 7.3 vs. 14.9 ± 13.1 ms/mmHg) or sympathetic baroreflex sensitivity (−1.06 ± 0.65 vs. −0.97 ± 0.54 au/mmHg) remained unchanged from baseline at the period of inhalation. Heart rate and respiratory variables remained unchanged in both trials.ConclusionsThe fragrance stimulation of Grapefruit essential oil increased BP without increase in MSNA nor modulating cardiovagal and sympathetic control of BP in humans.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Phthalate exposure and high blood pressure in adults: a cross-sectional study in China.

Widespread phthalate exposure has been recently documented and is hypothesized to increase blood pressure (BP) in humans. However, current studies have provided inconclusive evidence for an association between phthalate exposure and BP. Human epidemiologic studies on the topic remain lacking. Therefore, this study aims to examine the association between serum phthalate concentrations and BP in a Chinese population. We measured several parameters of BP (systolic BP, diastolic BP, total cholesterol, and triglyceride) and the concentrations of 16 phthalates (dimethyl phthalate (DMP), diethyl phthalate, diisobutyl phthalate, dibutyl phthalate (DBP), bis (2-methoxyethyl) phthalate, bis (4-methyl-2-pentyl) phthalate, bis (2-ethoxyethyl) phthalate, diamyl phthalate, dihexyl phthalate, benzyl butyl phthalate, bis (2-nbutoxyethyl) phthalate (DBEP), dicyclohexyl phthalate, bis (2-ethyl hexyl) phthalate (DEHP), diisononyl phthalate, diphenyl phthalate, and di-n-octyl phthalate) in the serum of 474 adults recruited from a primary health care clinic. The relationship between serum phthalate concentrations and BP parameters was assessed with multivariate linear regressions. DBP was the most ubiquitous and dominant contaminant in the study population. The systolic BP of subjects in the median-exposure DEHP group significantly increased by 2.96mmHg (p < 0.05) relative to that of subjects in the low-exposure group. Significant positive dose-related associations of DMP and DBEP with the levels of total cholesterol in serum (p for trend < 0.05) were also found. These associations persisted even when considering exposure to multiple phthalates. Our results suggested that phthalate exposure might increase BP in adults. However, our findings warrant further studies in a larger and more general population.

The haemodynamic response to incremental increases in negative intrathoracic pressure in healthy humans.

What is the central question of this study? The haemodynamic response to incremental increases in negative intrathoracic pressure (nITP) during spontaneous breathing and the mechanisms of cardiac impairment at these levels of nITP remain unclear. What is the main finding and its importance? nITP of -20cmH2 O or greater reduces stroke volume in healthy, spontaneously breathing supine humans due to direct ventricular interaction and increased left ventricular afterload. Negative intrathoracic pressure (nITP) generally augments venous return and left ventricular (LV) stroke volume (LVSV), though large increases in nITP, commonly seen in respiratory disease, attenuate LVSV. Despite this consistent finding, the degree of nITP required to reduce LVSV and the contributions of series and direct ventricular interaction (DVI) in mediating this response remain unclear. We hypothesized that nITP ≤-15cmH2 O would augment LVSV, while nITP ≥-20cmH2 O would reduce LVSV via DVI and increased afterload. Twenty-three healthy subjects were randomly given inspiratory loads during spontaneous breathing to generate -5, -10, -15, -20 and -25cmH2 O. LV volumes, LV geometry, inferior vena cava collapsibility (cIVC) and LV end-systolic meridional wall-stress (LVESMWS) were assessed in the supine position using tri-plane echocardiography. LVSV remained unchanged up to -15cmH2 O, but was significantly reduced at nITP ≥-20cmH2 O (-12±8% and -15±11% at -20 and -25cmH2 O, respectively, P<0.05) due to significant reductions in LV end-diastolic volume (LVEDV), while LV end-systolic volume was unchanged. cIVC on inspiration was significantly increased at all levels of nITP, while LVESMWS only increased at -25 cmH2 O (P<0.05). DVI, as indicated by a significant increase in the radius of septal curvature, occurred at nITP ≥-10cmH2 O. In supine healthy humans, nITP ≤-15cmH2 O does not significantly affect LV function, despite increased DVI. In contrast, nITP ≥-20cmH2 O causes significant reductions in LVSV and LVEDV, which appear to be mediated by DVI and increased afterload at -25cmH2 O. The impact of cIVC during nITP remains unclear.

Effects of ninety minutes per week of continuous aerobic exercise on blood pressure in hypertensive obese humans.

The main objective of this study was to examine the effect of continuous aerobic training (CAT) in hypertensive, obese people. Seven patients of average age (45.3±3.9 years), height (1.63±0.1 m), body weight (89.09±22.0 kg), and body mass index (33.44±8.6 kg/m2) were subjected to the training. CAT was performed in thrice-weekly nonconsecutive sessions (90 min per week) with intervals of 48 hr between each session. The training sessions entailed 30 min of walking at an intensity of 70%–80% of the maximum heart rate (MHR) on a treadmill over a period of eight weeks, giving a total of 24 sessions. Through correlation analyses, we found significant improvement in the systolic pressure (R=0.5675, P=0.0253) and diastolic pressure (R=0.7083, P=0.0088) when the last session was compared to the first session of training. We found no differences in the diastolic pressure and systolic pressure before, during and after 15 min of the protocol exercise. The program showed a large effect size (ES) for systolic pressure (ES=0.85) and a small ES for diastolic pressure (ES=0.33). We found no differences in the blood pressure (BP) and heart rate (HR) during and after the training of obese hypertensive humans, but we found a positively significant correlation between HR and BP in the last session and a large ES, suggesting that this protocol exercise might have significance effect in the long term.

High-Density Lipoprotein Function in Cardiovascular Disease and Diabetes Mellitus.

Cardiovascular disease (CVD) is the most common cause of death worldwide.1 Major CVD risk factors are hypertension, smoking, physical inactivity, abnormal glucose levels/diabetes mellitus, and dyslipidemia. Among these, dyslipidemia characterized by a low level of HDL-C (high-density lipoprotein cholesterol) is strongly and inversely correlated with CVD risk,2–4 and low HDL-C levels is part of the atherogenic dyslipidemia complex associated with diabetes mellitus.5 These observations triggered intense interest in increasing HDL-C levels for therapeutic intervention of CVD.6,7 However, several recent lines of evidence now suggest that the association between HDL-C levels and CVD status may be indirect or more complicated than previously recognized.7 Thus, human genetic studies demonstrate that genetically altered HDL-C levels do not necessarily translate to an altered risk of CVD.8–12 Phase III clinical trials of drugs that elevate HDL-C, such as niacin and CETP (cholesteryl ester transfer protein) inhibitors, also have largely failed to reduce CVD events in statin-treated subjects with established CVD.13–15 For several CETP inhibitors, improvement in CVD prevention was unsuccessful because of off-target effects (torcetrapib) or lack of efficacy (dalcetrapib and evacetrapib).14,16–18 The exception is the recent REVEAL trial (Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification), which included more subjects and was performed for longer than previous CETP inhibitor trials. The REVEAL demonstrated that the CETP inhibitor anacetrapib exhibited beneficial effects on cardiovascular outcomes on top of those of statin therapy, although the risk reduction was moderate19,20 and might have been due, at least in part, to a reduction in non-HDL-C rather than elevated HDL-C.21 Considering these cumulative observations, it remains uncertain whether increased HDL-C directly impacts atherosclerosis and the …

Differential effects of Bach's Orchestral Suite No. 3 on blood pressure and heart rate - a prospective controlled study

Background There is little known whether music of different styles can directly alter blood pressure (BP) and heart rate (HR) in humans. We studied the potential effects of Bach’s orchestral Suite No. 3 in comparison to silence (S [“controls CO]) on BP and HR.Objective To analyse the effect of different music styles (intervention group) on BP, HR and C compared to S (control group).Methods 120 volunteers aged 25-75 years were randomly assigned in the intervention group (n=60) or to a control group (n=60). Interventional music styles were the different parts of Bach’s Suite No. 3, BWV 1068 [Ouverture, Air, Gavotte, Bourrée, Gigue]). Sixty healthy volunteers served as “control group” (CO): they underwent an identical study protocol but without music application.Results In studied volunteers, systolic, diastolic BP (mm Hg) and HR (min-1) decreased when Bach was played compared to CO (p&lt;0.001). Prior to the study BPsyst was 128.3+11.3 mm Hg, BPdiast was 81.9+7.9 Hg and HR was 75.3+12.0 bpm. After sound exposure or in CO the following results were observed (table). *p&lt;0.001, ap=0.01, bp=0.08 BPsyst (mm Hg) BPdiast (mm Hg) HR (min-1)Ouverture 120.9+12.4* 76.9+8.8* 69.8+11.2*Air 121.1+12.4* 77.1+7.9* 68.4+9.4*Gavotte 120.9+12.6* 77.0+8.9* 68.5+9.8*Bourrée 120.6+13.7* 76.5+9.4* 66.4+8.4*Gigue 120.4+15.2* 78.5+11.1* 68.1+9.2*Controls 120.6+8.7a 75.4+5.5b 78.8+11.9*Conclusions The results provide clear evidence for the potential of Bach’ music styles to influence cardiovascular parameters. All parts of the Suite No. 3 lead to decreased values of BP and HR. In the control group we could not observe similar findings.Trial registration German Clinical Trials Register (DRKS00009835)Funding: None