Pressure In Humans Research Articles

Protective Role of α-Calcitonin Gene-Related Peptide in Cardiovascular Diseases

α-Calcitonin gene-related peptide (α-CGRP) is a regulatory neuropeptide of 37 amino acids. It is widely distributed in the central and peripheral nervous system, predominantly in cell bodies of the dorsal root ganglion (DRG). It is the most potent vasodilator known to date and has inotropic and chronotropic effects. Using pharmacological and genetic approaches, our laboratory and other research groups established the protective role of α-CGRP in various cardiovascular diseases such as heart failure, experimental hypertension, myocardial infarction, and myocardial ischemia/reperfusion injury (I/R injury). α-CGRP acts as a depressor to attenuate the rise in blood pressure in three different models of experimental hypertension: (1) DOC-salt, (2) subtotal nephrectomy-salt, and (3) L-NAME-induced hypertension during pregnancy. Subcutaneous administration of α-CGRP lowers the blood pressure in hypertensive and normotensive humans and rodents. Recent studies also demonstrated that an α-CGRP analog, acylated α-CGRP, with extended half-life (~7 h) reduces blood pressure in Ang-II-induced hypertensive mouse, and protects against abdominal aortic constriction (AAC)-induced heart failure. Together, these studies suggest that α-CGRP, native or a modified form, may be a potential therapeutic agent to treat patients suffering from cardiac diseases.

Heat Acclimation Causes Profound Post-Exercise Hypotension and Favorable Improvements in Lipid and Immune Profiles

PURPOSE: We have previously reported that passive hyperthermic exposure causes an acute hypotensive response. The animal literature has shown that chronic heat stress causes alterations in metabolic and lipid metabolism. However, it is unknown if heat acclimation also causes chronic blood pressure and lipid responses in humans. This project tested the hypothesis that 10-day exercise-heat acclimation (HA) would cause greater post-exercise hypotensive responses and alter metabolic, lipid, and immune profiles compared to 10-day exercise under neutral conditions (CON). METHODS: Twelve healthy sedentary subjects (7M/5F, 28±6y, 78±17kg), completed a 10-day (90min/day exercise bout) clamp controlled (internal work-rate) hyperthermia HA (42°C, 28% RH) and control (CON: 23°C, 42% RH) protocols in a counterbalanced design separated by at least 2 months. Pre- and post-exercise HA/CON blood pressure was taken post-exercise over 1 hour after day 1 and day 10 exercise. Metabolic, lipid and immune panels were taken pre-post HA/CON. RESULTS: Exercise under heat stress had greater post-exercise hypotension (systolic; -6mmHg, diastolic -8mmHg; and mean arterial pressure, -7mmHg) on day 1 and day 10 compared to exercise under neutral conditions (main effect for condition, P≤0.004). Only from pre-to-post HA, total cholesterol (170±22 to 152±15; P<0.02) and triglycerides (130±63 to 93±27; P<0.03) were reduced. A trend for changes in glycemic control (%A1c; 5.4±0.3 to 5.3±0.4; P<0.06) neutrophils (52.3±5.6% to 57.5±4.0%; P<0.09), lymphocytes (37.9±5.7% to 32.9±3.0; P<0.07), and eosinophils (2.4±1.7 to 3.1±0.1; P<0.06) were found after HA. CONCLUSIONS: These preliminary data indicate that HA causes a profound post-exercise hypotensive response and favorable metabolic, lipid, and immune profile changes. Further examination of heat acclimation on vascular, metabolic, and immune responses will offer insight for benefits in other clinical populations with vascular, metabolic and immune dysfunction.

Measurement of Blood Pressure in Humans: A Scientific Statement From the American Heart Association.

The accurate measurement of blood pressure (BP) is essential for the diagnosis and management of hypertension. This article provides an updated American Heart Association scientific statement on BP measurement in humans. In the office setting, many oscillometric devices have been validated that allow accurate BP measurement while reducing human errors associated with the auscultatory approach. Fully automated oscillometric devices capable of taking multiple readings even without an observer being present may provide a more accurate measurement of BP than auscultation. Studies have shown substantial differences in BP when measured outside versus in the office setting. Ambulatory BP monitoring is considered the reference standard for out-of-office BP assessment, with home BP monitoring being an alternative when ambulatory BP monitoring is not available or tolerated. Compared with their counterparts with sustained normotension (ie, nonhypertensive BP levels in and outside the office setting), it is unclear whether adults with white-coat hypertension (ie, hypertensive BP levels in the office but not outside the office) have increased cardiovascular disease risk, whereas those with masked hypertension (ie, hypertensive BP levels outside the office but not in the office) are at substantially increased risk. In addition, high nighttime BP on ambulatory BP monitoring is associated with increased cardiovascular disease risk. Both oscillometric and auscultatory methods are considered acceptable for measuring BP in children and adolescents. Regardless of the method used to measure BP, initial and ongoing training of technicians and healthcare providers and the use of validated and calibrated devices are critical for obtaining accurate BP measurements.

Impact of slow breathing on the blood pressure and subarachnoid space width oscillations in humans

The aim of the study was to assess cardiac and respiratory blood pressure (BP) and subarachnoid space (SAS) width oscillations during the resting state for slow and fast breathing and breathing against inspiratory resistance. Experiments were performed on a group of 20 healthy volunteers (8 males and 12 females; age 25.3 ± 7.9 years; BMI = 22.1 ± 3.2 kg/m2). BP and heart rate (HR) were measured using continuous finger-pulse photoplethysmography. SAS signals were recorded using an SAS monitor. Oxyhaemoglobin saturation (SaO2) and end-tidal CO2 (EtCO2) were measured using a medical monitoring system. Procedure 1 consisted of breathing spontaneously and at controlled rates of 6 breaths/minute and 6 breaths/minute with inspiratory resistance for 10 minutes. Procedure 2 consisted of breathing spontaneously and at controlled rates of 6, 12 and 18 breaths/minute for 5 minutes. Wavelet analysis with the Morlet mother wavelet was applied for delineation of BP and SAS signals cardiac and respiratory components. Slow breathing diminishes amplitude of cardiac BP and SAS oscillations. The overall increase in BP and SAS oscillations during slow breathing is driven by the respiratory component. Drop in cardiac component of BP amplitude evoked by slow-breathing may be perceived as a cardiovascular protective mechanism to avoid target organ damage. Further studies are warranted to assess long-term effects of slow breathing.

Key genes differential expressions and pathway involved in salt and water-deprivation stresses for renal cortex in camel

BackgroundCamels possess the characteristics of salt- and drought-resistances, due to the long-time adaption to the living environment in desert. The camel resistance research on transcriptome is rare and deficient, especially reabsorption in renal cortex. Non-coding RNAs are normally considered as the RNA molecules that are not translated into proteins, their current roles remain mostly in regulation of information flux from DNA to protein, further on normal life activities and diseases. In order to reveal the mysterious veil of the post-transcriptional regulation of ncRNAs in renal cortex for the first time as far as we know, we designed and carried out the experiment of salt stress and water-deprivation stress in camel.ResultsBy means of RNA-seq in renal cortex of Alxa Bactrian Camel (Camelus bactrianus), we identified certain significantly differential RNAs, including 4 novel lncRNAs, 11 miRNAs and 13 mRNAs under salt stress, 0 lncRNAs, 18 miRNAs and 14 mRNAs under water-deprivation stress. By data analysis, the response pathway of post-transcriptional regulation concerning salt and water-deprivation stresses was put forward, involving preventing sodium from entering the cell, purifying of water and compensating neutral amino acids by miR-193b, miR-542-5p interaction with SLC6A19 mRNA.ConclusionBased on the resistance-related lncRNAs, miRNAs, and mRNAs, we proposed the post-transcriptional regulation pathway to explain how camels respond to salt and water-deprivation stresses in the ncRNAs regulation level of renal cortex for the first time, thus hoping to provide a theoretical basis for therapy of disease that is similar to high blood pressure in humans.

Loss of reticulocalbin 2 lowers blood pressure and restrains ANG II-induced hypertension in vivo.

Hypertension affects over 1 billion people worldwide and increases the risk for heart failure, stroke, and chronic kidney disease. Despite high prevalence and devastating impact, its etiology still remains poorly understood for most hypertensive cases. Rcn2, which encodes reticulocalbin 2, is a candidate gene for atherosclerosis that we have previously reported in mice. Here, we identified Rcn2 as a novel regulator of blood pressure in mice. Rcn2 was abundantly expressed in the endothelium and adventitia of normal arteries and was dramatically upregulated in the medial layer of the artery undergoing structural remodeling. Deletion of Rcn2 lowered basal blood pressure and attenuated ANG II-induced hypertension in C57BL/6 mice. siRNA knockdown of Rcn2 dramatically increased production of the nitric oxide (NO) breakdown products nitrite and nitrate by endothelial cells but not by smooth muscle cells. Isolated carotid arteries from Rcn2-/- mice showed an increased sensitivity to the ACh-induced NO-mediated relaxant response compared with arteries of Rcn2+/+ mice. Analysis of a recent meta-data set showed associations of genetic variants near RCN2 with blood pressure in humans. These data suggest that Rcn2 regulates blood pressure and contributes to hypertension through actions on endothelial NO synthase.

Spectral Power of Slow Wave Sleep is Associated with Reductions of Nocturnal Blood Pressure in Humans

Slow wave sleep (SWS) is characterized by high amplitude, low frequency waveforms oscillating at 0.5 to 4 Hz. These slow wave oscillations, also referred to as delta waves, have been implicated as an important component of cardiovascular health. Specifically, SWS is associated with sympathoinhibition and decreased blood pressure, and studies suggest the greatest reductions of nocturnal blood pressure during SWS. Recent studies report that the strength of SWS, quantified using spectral analysis of the delta waves and referred to as delta power density, is related to clinical conditions such as fibromyalgia and depression. To date, the impact of delta power density on nocturnal blood pressure remains unknown. We hypothesized that delta power density would be greater during the first cycle of SWS compared to the second cycle of SWS, and that this would be associated with greater reductions of nocturnal blood pressure. Eight participants (5 female, 23 ± 1 years, 29 ± 2 kg/m2) were equipped with overnight finger plethysmography (NOVA, Finapres) and a standard 10–20 electroencephalography (EEG) for quantification of sleep stages. Overnight EEG was scored by a board certified sleep technician. EEG signals were filtered with a low pass (35 Hz), high pass (0.5 Hz), and notch filter (60 Hz). Central leads (C3 and C4) were analyzed using an original Matlab® code, applying a short‐term Fourier transform function (i.e., spectral analysis) with sliding window parameters of 10 seconds by 5 seconds to detect delta frequencies (i.e., 0.5 to 4 Hz). Delta frequencies were normalized to the entire overnight EEG to quantify delta power density. Beat‐to‐beat systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and heart rate (HR) were compared across a wake baseline (minimum 5 min), the first SWS cycle (18 ± 3 min), and the second SWS cycle (40 ± 13 min) using repeated measures ANOVA (p&lt;0.05). Pearson correlations were used to compare changes of delta power density with changes in blood pressure between SWS cycles 1 and 2. SAP was significantly reduced during the first (111 ± 3 to 96 ± 4 mmHg; p = 0.01), but not second (108 ± 5 mmHg), cycle of SWS when compared to the wake baseline. In contrast, DAP was significantly reduced during both the first (68 ± 3 to 56 ± 3 mmHg; p &lt; 0.02) and second (61 ± 5 mmHg; p = 0.03) cycles of SWS. HR was not statistically different between wake and either cycle of SWS. Delta power density was not different between SWS cycles, but changes in delta power density across SWS cycles was significantly correlated with changes in SAP (r = −0.69, p = 0.03) and DAP (r = −0.71, p = 0.02). Our findings indicate that the strength of SWS, as quantified by delta power density, is significantly associated with greater reductions in nocturnal blood pressure. These results support emerging evidence that sleep is important to cardiovascular health and that the strength of SWS is of particular relevance. This has potential clinical implications, as there are a number of conditions and drugs that can diminish slow wave sleep.Support or Funding InformationSupport provided by the National Institutes of Health (AA‐024892) and the Portage Health Foundation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of Acute Dietary Nitrate Supplementation on Exercise Blood Flow in Hypertension: Does Medication Status Matter?

Dietary nitrates are effective at lowering resting blood pressure (BP) in humans and improving skeletal muscle blood flow (BF) during exercise in animals. However, evidence of improved BP status and BF during exercise in hypertension is lacking. The purpose of this investigation was to determine if acute (3‐day) nitrate supplementation with beetroot juice (BR) lowers BP and augments BF in hypertensive individuals on and off antihypertensive medication during progressive handgrip (HG) and single‐leg knee extension (KE) exercise. In a double blind crossover study, placebo (nitrate depleted BR) and BR were administered in 14 subjects with controlled hypertension (ON‐MEDS; 53±11 yrs., 11 men, 3 women) and 14 subjects not taking antihypertensive medications (OFF‐MEDS; 49±13 yrs., 11 men, 3 women). Following either 3 days of BR or placebo supplementation, participants performed HG (15, 30, 45% of maximal voluntary contraction [MVC]) and single‐leg KE exercise (40, 60, 80% of work rate maximum [WRmax]). When OFF‐MEDs, BR significantly reduced resting diastolic BP (DBP) (BR: 84 ± 3 vs. PL: 88 ± 3 mmHg; p &lt; 0.01) and mean arterial pressure (MAP) (BR: 101 ± 3 vs. PL: 106 ± 3 mmHg; p &lt; 0.01), with systolic BP (SBP) trending lower (BR: 136 ± 4 vs. PL: 141 ± 5 mmHg; p = 0.067). BR did not change resting BP for the ON‐MEDS group. During HG exercise, BR supplementation only lowered SBP at 15% MVC (p &lt; 0.05) and 30% MVC (p = 0.05) when OFF‐MEDS, with no effect on BF or vascular conductance (VC). During KE exercise, in the OFF‐MEDS group, BR significantly lowered SBP and MAP at 80% WRmax, but not at the lower intensities. When OFF‐MEDS, BR significantly increased leg BF at 40% WRmax (BR: 2667 ± 173 vs. PL: 2461 ± 193 ml/min; p = 0.04) and leg VC at 40% (BR: 24 ± 2 vs. PL: 21 ± 1 ml/min/mmHg; p &lt; 0.01) and 60% (BR: 27 ± 2 vs. PL: 25 ± 2 ml/min/mmHg; p &lt; 0.03) WRmax. When ON‐MEDS, BR did not alter BP, BF or VC during HG or KE exercise. These findings reveal that BR can lower BP at rest and during exercise, as well as augment the blood flow response during leg exercise in unmedicated hypertensive individuals, suggesting a potential benefit of BR to this population.Support or Funding InformationThis study was supported by Veteran Affairs Rehabilitation Research and Development Grant IK2RX001215 CDA2 (to J. D. Trinity) and American Heart Association Grant 14SDG1850039 (to J. D. Trinity)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Acetazolamide Administration Restores the Blood Pressure Lowering Effect of Tempol in Female SHR

The mechanisms responsible for the sex differences in blood pressure (BP) in humans are not clear. Over the past several years, we have studied the spontaneously hypertensive rat (SHR) as a model of sex differences in BP control. Oxidative stress (OS) plays a major role in BP regulation in preclinical studies. There is a sex difference in the BP responses to pro‐oxidants and antioxidants in the SHR. In contrast to males, BP in female SHR does not decrease in response to Tempol or Apocynin. Acetazolamide (Aceta) inhibits proximal tubular sodium reabsorption, increasing sodium delivery to the distal tubule which increases distal tubule OS. We tested the hypothesis that an increase in sodium delivery in the distal tubule will restore the BP lowering effects of Tempol in female SHR.Materials and MethodsFemale SHR, aged twenty weeks, were implanted with radiotelemetry transmitters and following a two week recovery period, baseline mean arterial pressure (MAP) was measured 24 hrs per day. All rats were then given Aceta (100 mg/kg/day sc) for 14 days (n=14). After this period, a group of rats were randomized to receive Tempol (1mmol/L) in drinking water for an additional two weeks (Aceta + Tempol) (n=7/grp) and BP was compared to controls who received Aceta only (n=7/grp). MAP was measured continuously throughout the treatment periods.ResultsAt baseline, MAP was similar in both groups of female SHR (144 ± 1 vs. 145 ± 1 mmHg). Aceta administration for two weeks caused a 10 mmHg reduction in MAP, which was similar in both group of rats (132 ± 1 vs. 131 ± 1 mmHg, p=0.43). Tempol administration significantly lowered MAP in presence of Aceta (138 ± 1vs. 122 ± 1 mmHg, p&lt;0.0001). Body weight was similar between Aceta and Aceta + Tempol groups (200.3 ± 2.0g vs. 192.2 ± 4.0 g).In conclusion, our data suggest that there are sex differences in proximal sodium reabsorption that may impact OS in SHR. By increasing sodium delivery to the distal nephron with acetazolamide, the BP lowering effect of Tempol is restored in female SHR. These data suggest that different mechanisms may control oxidative stress and blood pressure in male and female SHR.Support or Funding InformationThis project was funded by NIH R01 HL135089, P20 GM12334, &amp; PO1HL51971This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The availability of sympathetic neurotransmitter release for nerve stimulation is enhanced in mesenteric arteries from long‐term paraplegic and tetraplegic rats

Loss of supraspinal inputs to sympathetic preganglionic neurons causes a marked reduction in post‐ganglionic sympathetic vasoconstrictor nerve activity and sympathetic support of blood pressure in both humans and rats with spinal cord injury (SCI). The long‐term impact of this reduced sympathetic outflow on sympathetic neurotransmission is unknown. We investigated this question using established long‐term animal models of paraplegic (P, T2–3) and tetraplegic (T, C6–7) SCI in male Sprague Dawley rats (26 weeks in total age). Sixteen weeks after SCI, P and T rats showed significantly lower blood pressure than sham operated rats (P 103±2mmHg, T 97±4mmHg, sham 117±6mmHg) (P&lt;0.05 P or T vs sham). P rats had faster heart rate (410±6bpm), while T rats had slower heart rate (299±10bpm) than sham rats (321±14bpm) (P&lt;0.05, P or T vs sham). P and T rats also showed lower body weight than sham rats (P 380±5g, T 340±12g, sham 459±18g) (P&lt;0.05, P or T vs sham). Small mesenteric arteries (MA) were collected from these rats for detailed examination of sympathetic neurotransmission. Norepinephrine (NE) release from sympathetic nerve terminals was measured using amperometry. ATP release was determined indirectly by measuring excitatory junction potentials (EJPs) in MA smooth muscle cells. Frequency dependent NE release curves in response to nerve stimulation were slightly leftward‐shifted in MA from P and T rats compared to sham rats. Interestingly, frequency dependent EJP response curves to nerve stimulation in MA of P and T rats were shifted markedly leftward and upward compared to sham rats; and responses in these rats also showed significant initially facilitation of EJPs during long‐train nerve stimulation. In pressurized MA, exogenous NE and ATP‐induced contractions were comparable in all rats. Immune staining of tyrosine hydroxylase in MA showed comparable sympathetic nerve density and distribution in all rats. NE content in tissues from left ventricle, kidney, spleen and MA were measured by HPLC. Compared to sham rats, NE content in left ventricle from P and T rats, and in MA from T rats, was significantly increased. NE content in MA from P rats was not different from sham rats, and NE content in kidney and spleen from P and T rats did not differ from sham animals. Our studies show that peripheral vascular NE, and especially ATP, release is enhanced during nerve stimulation 16 weeks after SCI, whereas post‐ganglionic nerve density and arterial reactivity to sympathetic neurotransmitters are unchanged. Even though overall sympathetic support of blood pressure is reduced after SCI, improvement in sympathetic neurotransmitter release may help maintain cardiovascular stability in long‐term SCI subjects. (Supported by NHLBI 2P01HL070687 and HL122223).Support or Funding InformationNHLBI 2P01HL070687 and HL122223This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of Fragrance Inhalation of Grapefruit Essential Oil on Blood Pressure and Baroreflex Sensitivity in Human with, and without, Family History of Hypertension

PurposeFragrance inhalation of essential oils used in aromatherapy can affect blood pressure (BP) and autonomic nervous system in humans. Considerably wide individual variations have been observed in the response, but the background factors behind the wide individual variations remain unknown. Previous studies have reported that resting circulatory variables and baroreflex sensitivity, and also the response of BP and muscle sympathetic nerve activity with mental stress and upright tilting are different between subjects with and without family history of hypertension (FH). We tested the hypothesis that the response of BP with fragrance inhalation of grapefruit essential oil (GF) was different between subjects with (FH+) and without FH (FH−).MethodsEighteen healthy subjects participated in this study (FH+, n = 8; FH−, n = 10). While subjects in the supine position, they breathed blank air through a face mask for 10 min as baseline (BL). Then, they inhaled air with the fragrance of GF from Douglas bags for 10 min. Beat‐by‐beat heart rate and BP were recorded continuously. Cardiovagal baroreflex sensitivity was determined with data for the last 2 min of each stage, as the slope of the liner regression between beat‐by‐beat changes in systolic BP and R‐R interval.ResultsAt 6 to 10 min of BL, heart rate, systolic and diastolic BP was not significantly different between FH+ group and FH− group. During GF inhalation, diastolic BP in FH− group increased significantly (p &lt; 0.05) from BL whereas it remained unchanged in FH+ group. Systolic BP and heart rate remained unchanged during GF inhalation in both groups. There were no significant changes in baroreflex sensitivity with fragrance inhalation in both groups.ConclusionsThe FH is a possible background factor behind the individual variation observed in the response of BP with fragrance inhalation of GF.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cardiac output during exercise is related to plasma atrial natriuretic peptide but not to central venous pressure in humans.

What is the central question of this study? Is cardiac output during exercise dependent on central venous pressure? What is the main finding and its importance? The increase in cardiac output during both rowing and running is related to preload to the heart, as indicated by plasma atrial natriuretic peptide, but unrelated to central venous pressure. The results indicate that in upright humans, central venous pressure reflects the gravitational influence on central venous blood rather than preload to the heart. We evaluated the increase in cardiac output (CO) during exercise in relationship to central venous pressure (CVP) and plasma arterial natriuretic peptide (ANP) as expressions of preload to the heart. Seven healthy subjects (four men; mean ± SD: age 26±3years, height 181± 8cm and weight 76±11kg;) rested in sitting and standing positions (in randomized order) and then rowed and ran at submaximal workloads. The CVP was recorded, CO (Modelflow) calculated and arterial plasma ANP determined by radioimmunoassay. While sitting, (mean±SD) CO was 6.2±1.6lmin-1 , plasma ANP 70±10pgml-1 and CVP 1.8±1.1mmHg, and when standing decreased to 5.9±1.0lmin-1 , 63±10 pgml-1 and -3.8±1.2mmHg, respectively (P<0.05). Ergometer rowing elicited an increase in CO to 22.5±5.5lmin-1 as plasma ANP increased to 156±11 pgml-1 and CVP to 3.8±0.9mmHg (P<0.05). Likewise, CO increased to 23.5±6.0lmin-1 during running, albeit with a smaller (P<0.05) increase in plasma ANP, but with little change in CVP (-0.9±0.4mmHg). The increase in CO in response to exercise is related to preload to the heart, as indicated by plasma ANP, but unrelated to CVP. The results indicate that in upright humans, CVP reflects the gravitational influence on central venous blood rather than preload to the heart.

Fabrication of N-doped multidimensional carbon nanofibers for high-performance cortisol biosensors

Cortisol is an hormone that regulates blood pressure, glucose levels and carbohydrate metabolism in humans. Abnormal secretion of cortisol can cause various symptoms closely linked to psychological and physical health. In this study, high-performance field-effect transistor (FET)-based biosensors for cortisol detection were fabricated from N-doped multidimensional carbon nanofibers. Nanofiber morphology was controlled by tailoring the pressure conditions during vapor deposition polymerization (VDP). Thereafter, conductive channels of FET were completed by thermal annealing, acid treatment, and antibody attachment. Changes associated with chemical processes were characterized by various instruments. The resulting transducers exhibited a rapid response toward cortisol molecules with accurate selectivity, stable reusability, and high sensitivity. Minimum detection level were as low as 100 aM with a wide linear detection range of 100 aM to 10 nM due to the large surface area of the transducer and a correspondingly high number of antibody labels. The response and applicability of these cortisol biosensors were also assessed using saliva as a test matrix.

Aortic Arch Baroreceptor Stimulation in an Experimental Goat Model: A Novel Method to Lower Blood Pressure.

The effect of aortic baroreceptor stimulation on blood pressure manipulation was assessed using the goat species Capra aegagrus hircus. The aim of this study was to manipulate blood pressure with future intention to treat high blood pressure in humans. The ages of the animals ranged from 6 months to 2 years. A standard anesthesia protocol was used. A lateral thoracotomy was performed to gain access to the aortic arch. Data was collected with the Vigileo system. Pre stimulation blood pressure was compared with maximum post stimulation blood pressure values. Results were analyzed with the Wilcoxon signed rank test. In the study 38 animals were enrolled. Baroreceptor stimulation was performed for each animal using 3 different electrodes each of which emits an electrical impulse. In the pilot phase of the study, the median baseline blood pressure prior to stimulation of the baroreceptors was 110.8 mmHg. After stimulation the median blood pressure decreased to 88 mmHg. The average decrease in blood pressure was 22.8 mmHg. This decrease of blood pressure after stimulation of the baroreceptors is statistically significant (p < 0.0001) and the proof of concept was shown. During the extended phase all three probes had a significant effect on blood pressure lowering (p < 0.0001). The study confirmed that aortic baroreceptor stimulation has an effect on blood pressure lowering. This is a novel field of blood pressure manipulation. The hemodynamic effects of long-term aortic baroreceptor stimulation are unknown. Further investigations need to be done to determine whether a similar effect can be induced in different species such as primates and humans.

The effect of remote ischemic pre-conditioning on pulmonary vascular pressure and gas exchange in healthy humans during hypoxia

This study investigated whether rIPC alters the typical changes in pulmonary arterial pressure, pulmonary gas exchange associated with exercise in hypoxia. Methods16 healthy adults were randomized to either rIPC treatment (n = 8) or control (n = 8). Afterward, subjects performed supine ergometry at constant load (30 W, 40˜50 rpm) for 25 min during hypoxia (12.5% O2). Following a 90˜120 min rest, either rIPC or sham treatment was performed, which was then followed by post-assessment exercise. Throughout exercise, pulmonary arterial systolic pressure (PASP) and mean pulmonary arterial pressure (mPAP) were measured via echocardiography, while pulmonary gas exchange was being assessed. ResultsThe rICP group demonstrated improved PASP and mPAP (p < 0.05), whereas the control group did not. Additionally, breathing efficiency (VE/VCO2) and end-tidal CO2 (PETCO2) were improved in rIPC group (p < 0.05), but not in controls. ConclusionThese data suggest that rIPC contributes to reduced pulmonary arterial pressure, and improved pulmonary gas exchange during hypoxic exercise. However, follow-up studies are needed to apply these findings to patient care settings.

Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.

The thick ascending limb plays a key role in maintaining water and electrolyte balance. The importance of this segment in regulating blood pressure is evidenced by the effect of loop diuretics or local genetic defects on this parameter. Hormones and factors produced by thick ascending limbs have both autocrine and paracrine effects, which can extend prohypertensive signaling to other structures of the nephron. In this review, we discuss the role of the thick ascending limb in the development of hypertension, not as a sole participant, but one that works within the rich biological context of the renal medulla. We first provide an overview of the basic physiology of the segment and the anatomical considerations necessary to understand its relationship with other renal structures. We explore the physiopathological changes in thick ascending limbs occurring in both genetic and induced animal models of hypertension. We then discuss the racial differences and genetic defects that affect blood pressure in humans through changes in thick ascending limb transport rates. Throughout the text, we scrutinize methodologies and discuss the limitations of research techniques that, when overlooked, can lead investigators to make erroneous conclusions. Thus, in addition to advancing an understanding of the basic mechanisms of physiology, the ultimate goal of this work is to understand our research tools, to make better use of them, and to contextualize research data. Future advances in renal hypertension research will require not only collection of new experimental data, but also integration of our current knowledge.

Combined impact of green coffee bean extract consumption and concurrent training on arterial blood pressure in overweight and obese women

Context: Green coffee ingestion improves blood pressure in healthy humans, but the interactive effect of green coffee and exercise is unknown. Aims: The purpose was to determine the combined effect of green coffee bean extract (GCE) consumption and concurrent training (CT) on arterial blood pressure in overweight and obese women. Setting and Design: This study was an experimental pilot study, which was conducted in 2017. Materials and Methods: Among overweight and obese women of the Rasht city, 30 participants were allocated to three groups via simple randomization to receive treatment with GCE (125 mg, twice/day, before lunch and dinner), CT (four sessions aerobic-resistance training/week), or both. Systole blood pressure (SBP), diastole blood pressure (DBP), heart rate, and mean arterial pressure (MAP) were measured before and 48 h after interventions. Statistical Analysis Used: Mean and standard deviation, analysis of covariance, and paired sample t-test were used. Results: Heart rate decreased in all intervention groups (P 0.05). Conclusion: It seems that GCE, CT, or combination of both had a little effect for improving arterial blood pressure, and therefore, simultaneous effect of CT-GCE was not more effective than CT or GCE for improving the blood pressure in women with normal blood pressure.

Leptin Is Not Essential for Obesity-Associated Hypertension

Background and Objective: Hyperleptinemia is supposed to play a causal role in the development of obesity-associated hypertension, possibly via increased sympathetic tone. Hence patients with congenital leptin deficiency should be hypotensive and their low blood pressure should increase under leptin substitution. Subjects and Methods: To test this assumption, we examined ambulatory blood pressure, resting heart rate, Schellong test results, cold pressor test results, heart rate variability, catecholamine metabolites, and aldosterone levels in 6 patients with congenital leptin deficiency before as well as 2–7 days and 7–14 months after the start of leptin substitution. Ambulatory blood pressure was also examined in 3 patients with biallelic disease-causing variants in the leptin receptor gene. Results: Contrary to our expectations, even before leptin substitution, 1 patient with biallelic leptin receptor gene variants and 4 patients with leptin deficiency had been suffering from hypertension. Short-term substitution with leptin increased blood pressure further in 3 out of 4 patients (from 127.0 ± 11.7 to 133.8 ± 10.6 mm Hg), concomitant with an increase in resting heart rate as well as in heart rate during the Schellong test in all patients (from 87.6 ± 7.7 to 99.9 ± 11.0 bpm, p = 0.031, and from 102.9 ± 13.5 to 115.6 ± 11.3 bpm, p = 0.031, respectively). Furthermore, the systolic blood pressure response during the cold pressor test increased in 4 out of 6 patients. Unexpectedly, catecholamine metabolites and aldosterone levels did not increase. After long-term leptin substitution and weight loss, the resting heart rate decreased in 4 out of 6 patients compared to baseline, and in all patients below the heart rate seen immediately after the start of therapy (from 99.9 ± 11.0 to 81.7 ± 5.4 bpm; p = 0.031). Conclusions: These results show that obesity-associated hypertension does not depend on the presence of leptin. However, short-term leptin substitution can increase the blood pressure and heart rate in obese humans with leptin deficiency, indicating that leptin plays at least an additive role in obesity-associated hypertension. The mechanisms behind this are not clear but might include an increase in regional sympathetic tone.

Differences in regional grey matter volume of the brain are related to mean blood pressure and muscle sympathetic nerve activity in normotensive humans.

The brainstem plays a critically important role in the beat-to-beat control of blood pressure, as well as setting mean blood pressure (MBP). We recently showed that regional cerebral blood flow to specific brainstem nuclei is inversely related to resting MBP in healthy normotensive individuals. Here we tested the hypothesis that grey matter volume in these same nuclei, and areas above the brainstem to which they are connected, is also associated with resting MBP and muscle sympathetic nerve activity (MSNA). Structural MRI of the brain and recordings of MSNA and BP were collected in 54 healthy participants. Subjects were divided into a lower MBP group (mean ± SEM 78.8 ± 1.5 mmHg, n=27) and higher MBP group (96.6 ± 1.2 mmHg, n = 27), as well as into a lower MSNA (9.5 ± 0.8 bursts/min, n = 27) and higher MSNA (25.4 ± 1.2 bursts/min, n = 27) group. Regional grey matter volume was higher in the region of the rostral ventrolateral medulla, nucleus tractus solitarius, and medullary raphe in the group with higher MBP and correlated significantly with mean MBP across all participants. Grey matter volume was significantly higher in the dorsomedial hypothalamus and anterior and posterior cingulate cortices in the group with lower MSNA and was inversely related to MSNA across all participants. We conclude that small differences in MBP and MSNA are associated with significant differences in grey matter volume in cortical and subcortical regions known to be involved in blood pressure regulation, suggesting that these structural differences contribute to resting MBP and MSNA and can predict the establishment of hypertension.

A Synergistic Approach to the Real-Time Estimation of the Feet Ground Reaction Forces and Centers of Pressure in Humans With Application to Human–Robot Collaboration

This letter proposes a novel technique for the real-time estimation of the human feet ground reaction forces (GRFs) and centers of pressure (CoP) from the whole-body CoP and body configuration. The estimated variables are used for the estimation of the overloading torques in human joints during double support, with the aim to provide an evaluation of the human ergonomics while performing heavy manipulation tasks with a robot, or when exposed to an external force. The estimation of the feet GRFs and CoP is achieved using a synergistic approach that combines a simplified geometrical model of the whole-body CoP and a learning technique to address the underdetermined force distribution problem. First, a statically equivalent serial chain (SESC) model which enables the whole-body CoP estimation is identified. Then, the estimated whole-body CoP and the simplified body pose information are used for the training and validation of the learning technique. The displacements between the feet CoP estimated using the synergistic model and the values measured using insole sensors, along with the GRFs vectors are finally used for the estimation of the body overloading joint torques. The proposed synergistic model is first validated experimentally in five subjects. Next, its real-time efficacy is assessed in a human–robot load sharing task, in which the robot trajectories are optimized to minimize the effect of the external load on the human joints.