Larger Increases In Blood Pressure Research Articles

Pediatric blood pressure category predicts longitudinal blood pressure change in adolescence and early adulthood.

Patterns of blood pressure (BP) change from early adolescence to young adulthood have not been well-described. The objective of this study was to examine the predictive value of pediatric BP classification on BP change and identify subpopulations with large BP increases during adolescence and early adulthood. Baseline data were obtained from medical checkups of Japanese adolescents aged 12-13 years in 2009 or 2010 and subsequent BP values were followed for a 9-year period. Mixed-effects models were used to estimate the effects of baseline factors on subsequent BP changes. Hypertensive and elevated BP group consistently had higher BP values than normal BP group throughout the observation period. Multivariate mixed-effects model analyses revealed group-by-time interactions between systolic BP change and BP category in males and uric acid category in females, and between diastolic BP change and white blood cell count in males and obesity and high-density lipoprotein cholesterol in females; however, these factors had limited effects on the rate of BP increase, indicating that they are not suitable as clinical predictors of BP increase. Pediatric BP category predicted BP values, but there was no factor that identified subpopulations with large BP increases in adolescence and early adulthood. Blood pressure category in the American Academy of Pediatrics clinical practice guideline at age 12-13 years predicted subsequent blood pressure values during adolescence and early adulthood. No baseline factor that identified a subpopulation with large increase in blood pressure during adolescence and early adulthood in clinical practice was found. Our study contributes to the existing literature by demonstrating the usefulness of the American Academy of Pediatrics clinical practice guideline for blood pressure classification in a Japanese population.

Contribution of afferent renal nerve signals to acute and chronic blood pressure regulation in stroke-prone spontaneously hypertensive rats.

The activation of sympathetic nervous system plays a critical role in the development of hypertension. The input from afferent renal nerves may affect central sympathetic outflow; however, its contribution to the development of hypertension remains unclear. We investigated the role of afferent renal nerves in acute and chronic blood pressure regulation using normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Acute chemical stimulation of afferent renal nerves elicited larger increases in blood pressure and renal sympathetic nerve activity in young 9-week-old SHRSP compared to WKY. Selective afferent renal denervation (ARDN) and conventional total renal denervation (TRDN) ablating both afferent and efferent nerves in young SHRSP revealed that only TRDN, but not ARDN, chronically attenuated blood pressure elevation. ARDN did not affect plasma renin activity or plasma angiotensin II levels, whereas TRDN decreased both. Neither TRDN nor ARDN affected central sympathetic outflow and systemic sympathetic activity determined by neuronal activity in the parvocellular region of hypothalamic paraventricular nucleus and rostral ventrolateral medulla and by plasma and urinary norepinephrine levels, respectively. Renal injury was not apparent in young SHRSP compared with WKY, suggesting that renal afferent input might not be activated in young SHRSP. In conclusion, the chronic input from afferent renal nerves does not contribute to the development of hypertension in SHRSP despite the increased blood pressure response to the acute stimulation of afferent renal nerves. Efferent renal nerves may be involved in the development of hypertension via activation of the renin-angiotensin system in SHRSP.

Comparison of effect of etomidate with propofol on hemodynamics during modified electroconvulsive therapy.

Background and Aims:Studies comparing the effect of propofol and etomidate on hemodynamic parameters during electroconvulsive therapy (ECT) have shown ambiguous results. Although some studies observed a larger increase in blood pressure and heart rate during the use of etomidate than propofol in ECT, whereas some studies have shown no difference in hemodynamic parameters with the use of etomidate or propofol. Most of the studies done to compare the hemodynamic effects of etomidate and propofol were limited by small sample size or retrospective in nature. Therefore, we conducted a prospective randomized trial to compare the effects of etomidate and propofol on hemodynamics during ECT.Material and Methods:A prospective randomized crossover study was conducted on 30 patients with American Society of Anesthesiologist physical status I and II, between age 18 and 65 years, suffering from a mental disorder as per International Classification of Diseases-10 and requiring bilateral ECT as per clinical decision of consultant psychiatrist. They were randomized to receive both the drugs for their successive ECT sessions and were subjected to evaluation after clubbing together the ECT sessions of propofol or etomidate as anesthetic agent.Results:Duration of motor seizures was significantly more in patients receiving etomidate, whereas patients receiving propofol had more stable hemodynamics.Conclusion:Though propofol maintains stable hemodynamics during MECT, yet clinical applicability of etomidate outstrips it by a reasonable margin due to its better effect on seizure parameters.

Abstract 9101: RVLM Microinjection to Explain the Role of Metabotropic Glutamate Receptors in the Regulation of Baseline Blood Pressure and Heart Rate in SHRSP

Introduction: Glutamate (Glu) is activated by the stimulation of its receptors. The microinjection of Glu in rostral ventrolateral medulla (RVLM) elicited a rapid and large increase in blood pressure (BP) and heart rate (HR), which is inhibited with kynurenic acid (KYN), a selective inhibitor of ionotropic glutamate receptors (iGluR). Further, we showed that the response to Glu was much greater in stroke-prone spontaneously hypertensive rats (SHRSP) than that in Wistar Kyoto (WKY) rats, indicating that iGluR in RVLM played an important role to maintain high BP & HR in SHRSP. Whereas, the role of metabotropic glutamate receptors (mGluR) in RVLM were not fully elucidated in SHRSP yet. Hypotheses: Since the different mGluR types, e.g., group I (mGluR1, mGluR5), group II (mGluR2, mGluR3) & group III (mGluR4, mGluR6, mGluR7, mGluR8), are expressed in the various regions of rat’s brain, and several studies reported that mGluR5 is largely expressed in RVLM of rats; in this study we evaluated the pathophysiological role(s) of mGluR5, expecting that mGluR5 in RVLM keeps high baseline (i) BP and (ii) HR in SHRSP. Method: MTEP (10 nmole, a highly selective mGluR5 antagonist) and KYN (4 nmole) were microinjected unilaterally in RVLM in SHRSP (n=10) and WKY (n=10) to determine the effects on baseline BP & HR. In addition, the effects of two inhibitors on response to Glu (5 nmole) microinjection were observed. Results: MTEP reduced baseline BP & HR significantly in SHRSP when compared to those in WKY (ΔMAP: -30±3 vs. -3±2 mmHg, ΔHR: -35±3 vs. -4±2 bpm, respectively, p< 0.05), but failed to attenuate a response to Glu microinjection. In contrast, KYN had no significant effects on baseline BP & HR in the two strains, whereas it showed an inhibitory effect on the response to microinjected Glu, which was significantly greater in SHRSP than that in WKY. Conclusions: This study suggested that mGluR5 in RVLM played a major role in the maintenance of high baseline BP & HR in SHRSP.

Abstract P136: Effects Of Sex Hormones On The Hemodynamic And Sympathetic Responses To Centrally Administered Tumor Necrosis Factor-α In Rats

Inflammation plays an important role in the pathophysiology of cardiovascular dysfunction and neurohumoral excitation in heart failure and hypertension. Growing evidence has demonstrated significant sex differences in the inflammatory response and immune processes, with estrogen exerting an anti-inflammatory effects and testosterone potentially having pro-inflammatory influence. We previously reported that central administration of tumor necrosis factor-α (TNF-α) elicited different effects on blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in male and female rats. Whether the sex steroids estrogen and testosterone contribute to the observed differences in TNF-α-induced hemodynamic and sympathetic responses remains unknown. We hypothesized that estrogen protects against TNF-α-induced sympathetic excitation and pressor responses while testosterone enhances these excitatory outcomes in response to TNF-α. Female or male Sprague Dawley rats (10-12 weeks) anesthetized with ketamine plus xylazine underwent bilateral ovariectomy or castration, respectively, 2 weeks prior to study. Sham-operated (Sham) female or male animals served as controls. TNF-α (100 ng) was administered intracerebroventricularly (ICV). BP (mmHg), HR (bpm) and RSNA (% change) were recorded in urethane anesthetized rats. In ovariectomized female rats (n=6), ICV TNF-α induced significantly (*p<0.05 vs. Sham) larger increases in BP (19.3 ± 1.4* vs. 12.8 ± 1.2 ), HR (76.3 ± 4.8* vs. 51.5 ± 4.3) and RSNA (104.8 ± 6.9* vs. 72.4 ± 5.1), compared with Sham-female rats, that began within 20-30 mins and peaked at 90-120 mins after ICV injection. In castrated male rats (n=6), ICV TNF-α-elicited significantly smaller increases in BP (15.2 ± 1.3* vs. 21.8 ± 1.6), HR (57.7 ± 4.2* vs. 82.6 ± 4.1) and RSNA (72.6 ± 4.3* vs. 110.3 ± 4.7), compared with Sham-male animals. These data indicate a distinct role of sex hormones estrogen and testosterone in central inflammation-driven cardiovascular and sympathetic activation and suggest a protective effect of estrogen and a harmful effect of testosterone in the development of hypertension and heart failure.

No Sex Differences in Cerebral Blood Velocity Responses During Resistance Exercise

IntroductionThe brain requires intricate regulation of blood flow to maintain adequate perfusion to the tissue. Resistance exercise (RE) causes large increases in mean arterial pressure that challenges the regulation of cerebral blood flow. It is unknown, however, if the sex differences in blood pressure regulation may alter how cerebral blood flow responds to the large increases in blood pressure induced during RE.PurposeTo determine if the cerebral blood velocity response during an acute bout of RE differs by sex.MethodsTwenty‐nine young, healthy adults (M/F: 17/12; 25 ± 5 yrs; 23.9 ± 3.3 kg/m2) performed 3 sets of 10 repetitions maximal isokinetic knee flexion/extension exercise. Systolic (SBP), diastolic (DBP), and mean (MAP) arterial pressure were measured using finger photoplethysmography and used to calculate pulse pressure (PP). Transcranial Doppler ultrasound (2 MHz) was used to measure right middle cerebral artery mean blood velocity (MCAmv) and calculate pulsatility index ([MCAsystolic ‐ MCAdiastolic velocity]/MCAmv). Conductance was calculated as MCAmv/MAP. The last 30‐sec of a 10‐min baseline and last 10‐sec of the 3rd RE set were averaged for analyses.ResultsOverall, females had higher MCAmv and conductance compared to males (p<0.05). SBP, DBP, MAP, PP, MCAmv increased and conductance decreased similarly for males and females during RE (p<0.05). Pulsatility index did not change during RE in either sex (p>0.05).ConclusionsThe blood pressure and cerebral hemodynamic response during RE was not different between sexes. These data suggest sex may not effect cerebrovascular responses to a large increase in blood pressure incurred during maximal RE in young healthy adults. Blood pressure and cerebral blood velocity responses at baseline and during an acute bout of resistance exercise in young adults. Male (n= 17) Female (n= 12) p for Interaction Baseline Resistance Exercise Baseline Resistance Exercise SBP (mmHg) * 124 ± 10 172 ± 18 123 ± 7 170 ± 27 0.92 DBP (mmHg) * 73 ± 7 99 ± 10 74 ± 7 103 ± 17 0.58 MAP (mmHg) * 93 ± 8 128 ± 13 96 ± 7 132 ± 10 0.80 PP (mmHg) * 52 ± 7 72 ± 11 50 ± 6 67 ± 14 0.42 MCA Mean Velocity (cm/sec) *, ‡ 55 ± 9 65 ± 12 70 ± 15 81 ± 30 0.89 MCA Pulsatility Index 0.90 ± 0.16 0.82 ± 0.14 0.81 ± 0.15 0.82 ± 0.27 0.27 Conductance (cm/sec/mmHg) *, ‡ 0.60 ± 0.09 0.51 ±0.10 0.74 ± 0.17 0.62 ± 0.24 0.39 All data are presented mean ± standard deviation *Main effect for time (p<0.05) ‡Main effect for sex (p<0.05)

Sodium-activated potassium channels moderate excitability in vascular smooth muscle.

We report that a sodium-activated potassium current, IKNa , has been inadvertently overlooked in both conduit and resistance arterial smooth muscle cells. IKNa is a major K+ resting conductance and is absent in cells of IKNa knockout (KO) mice. The phenotype of the IKNa KO is mild hypertension, although KO mice react more strongly than wild-type with raised blood pressure when challenged with vasoconstrictive agents. IKNa is negatively regulated by angiotensin II acting through Gαq protein-coupled receptors. In current clamp, KO arterial smooth muscle cells have easily evoked Ca2+ -dependent action potentials. Although several potassium currents have been reported to play a role in arterial smooth muscle (ASM), we find that one of the largest contributors to membrane conductance in both conduit and resistance ASMs has been inadvertently overlooked. In the present study, we show that IKNa , a sodium-activated potassium current, contributes a major portion of macroscopic outward current in a critical physiological voltage range that determines intrinsic cell excitability; IKNa is the largest contributor to ASM cell resting conductance. A genetic knockout (KO) mouse strain lacking KNa channels (KCNT1 and KCNT2) shows only a modest hypertensive phenotype. However, acute administration of vasoconstrictive agents such as angiotensin II (Ang II) and phenylephrine results in an abnormally large increase in blood pressure in the KO animals. In wild-type animals Ang II acting through Gαq protein-coupled receptors down-regulates IKNa , which increases the excitability of the ASMs. The complete genetic removal of IKNa in KO mice makes the mutant animal more vulnerable to vasoconstrictive agents, thus producing a paroxysmal-hypertensive phenotype. This may result from the lowering of cell resting K+ conductance allowing the cells to depolarize more readily to a variety of excitable stimuli. Thus, the sodium-activated potassium current may serve to moderate blood pressure in instances of heightened stress. IKNa may represent a new therapeutic target for hypertension and stroke.

Abstract P3035: Role of T Cells in Sex Differences in Blood Pressure Elevation and Adipose Tissue Expansion Following Chronic High Fat Diet Feeding in Dahl Rats

Diets high in saturated fats are increasingly linked to the development of hypertension, yet the mechanisms by which high saturated fat diet (HFD) increases blood pressure remain unclear. Although young women are typically protected from hypertension relative to age-matched men, recent studies suggest that the cardiovascular protection in young women is compromised by chronic consumption of a HFD. We hypothesize that chronic HFD treatment causes a greater increase in blood pressure in females via sex-specific activation and recruitment of T cells and adipocyte expansion. Male and female Dahl rats (n=4-5) were placed on HFD at 8 wks of age. After 4 wks of HFD, blood pressure (BP) significantly increased in male and female Dahl rats to a comparable degree. Although BP continued to increase over the course of 10 wks of HFD treatment, female rats have a greater increases in BP (~40 mmHg increase in BP) after 10 weeks of HFD vs. males (~20 mmHg increase in BP). Fat pad weight and adipose tissue expansion increased in WT rats of both sexes following 10 wks of HFD treatment, yet females exhibited greater increases in fat pad weight and adipose tissue expansion vs. males. To determine whether T cells contributes to sex differences in BP elevation in Dahl rats fed HFD, we utilized Dahl rats lacking CD247 which encodes the T cell receptor CD3 chain that is required for T cell signaling. 10 wks of HF feeding did not change BP in either sex of Dahl CD247 KO rats. There were attenuated increases in fat pad weight and adipocyte expansion in Dahl CD247 KO rats and females exhibited more pronounced attenuations than males. Flow cytometric analysis revealed that HFD decreased Tregs and increased Th17 cells in both sexes of Dahl WT rats and females on HFD had the most pro-inflammatory T cell profile indicted by the Th17 cells:Tregs ratio. Our data suggest that greater adipocyte expansion with a HFD feeding in female Dahl rats vs. male might result in greater recruitment and activation of pro-inflammatory T cells and larger increases in BP.

Impaired dynamic cerebral autoregulation in trained breath-hold divers.

Breath-hold divers (BHD) experience repeated bouts of severe hypoxia and hypercapnia with large increases in blood pressure. However, the impact of long-term breath-hold diving on cerebrovascular control remains poorly understood. The ability of cerebral blood vessels to respond rapidly to changes in blood pressure represents the property of dynamic autoregulation. The current investigation tested the hypothesis that breath-hold diving impairs dynamic autoregulation to a transient hypotensive stimulus. Seventeen BHD (3 women, 11 ± 9 yr of diving) and 15 healthy controls (2 women) completed two or three repeated sit-to-stand trials during spontaneous breathing and poikilocapnic conditions. Heart rate (HR), finger arterial blood pressure (BP), and cerebral blood flow velocity (BFV) from the right middle cerebral artery were measured continuously with three-lead electrocardiography, finger photoplethysmography, and transcranial Doppler ultrasonography, respectively. End-tidal carbon dioxide partial pressure was measured with a gas analyzer. Offline, an index of cerebrovascular resistance (CVRi) was calculated as the quotient of mean BP and BFV. The rate of the drop in CVRi relative to the change in BP provided the rate of regulation [RoR; (∆CVRi/∆T)/∆BP]. The BHD demonstrated slower RoR than controls (P ≤ 0.001, d = 1.4). Underlying the reduced RoR in BHD was a longer time to reach nadir CVRi compared with controls (P = 0.004, d = 1.1). In concert with the longer CVRi response, the time to reach peak BFV following standing was longer in BHD than controls (P = 0.01, d = 0.9). The data suggest impaired dynamic autoregulatory mechanisms to hypotension in BHD. NEW & NOTEWORTHY Impairments in dynamic cerebral autoregulation to hypotension are associated with breath-hold diving. Although weakened autoregulation was observed acutely in this group during apneic stress, we are the first to report on chronic adaptations in cerebral autoregulation. Impaired vasomotor responses underlie the reduced rate of regulation, wherein breath-hold divers demonstrate a prolonged dilatory response to transient hypotension. The slower cerebral vasodilation produces a longer perturbation in cerebral blood flow velocity, increasing the risk of cerebral ischemia.

The Effects of Age and Cyclooxygenase Inhibition on the Cerebrovascular Response to a Metabolic Stimulus

BackgroundProstaglandins, such as cyclooxygenase (COX), may play an important role in regulating the cerebral blood flow response to a stimulus. We have previously shown that the vasodilatory response to a chemical stimulus decreases with age, and this difference is abolished by COX inhibition. However, the effects of COX inhibition on the cerebrovascular response to an increase in metabolic demand during a cognitive challenge is unknown. This information is important due to the frequent use of COX inhibitors for pain management. Thus, the purpose of this study was to determine the effect of COX inhibition on the cerebrovascular response to a metabolic stimulus in young and older adults.MethodsSeventy‐six participants, including 42 young adults (YA; 26 ± 5 y) and 34 older adults (OA; 64 ± 6 y) completed the Stroop Color Word Test, which is a test of executive function. A subset of 42 participants (n = 22 YA, n = 20 OA) also completed the N‐back Test, which is a test of working memory. Beat‐to‐beat middle cerebral artery velocity (MCAv) and mean arterial pressure (MAP) were measured at baseline and in response to each cognitive test. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. The response to each cognitive test was calculated as the peak percent change (%Δ) from baseline. Oral administration of the COX inhibitor Indomethacin (Indo) was given at 1.2mg/kg. Cognitive tests were then repeated after a 120‐minute wash‐in period.ResultsAt baseline, YA had higher MCAv, CVCi, and lower MAP (p<0.01 for all) compared to OA. There were no significant differences between groups in the %Δ from baseline during the Stroop or N‐back test (p>0.05). During Indo, YA had higher MCAv (p<0.01), CVCi (p<0.01), and lower MAP (p<0.05) compared to OA. Indo decreased baseline MCAv and CVCi in both groups (p<0.01 for all) but had no effect on MAP (p>0.05). During Indo, the %Δ in MCAv during Stroop and N‐back was lower in YA (p<0.01) compared to baseline in YA. During Indo, the %Δ in MCAv was lower during Stroop in OA (p<0.01), with a trend for significance in OA during N‐back (p=0.06) compared to baseline. In YA during Indo, the %Δ in MAP was lower during Stroop (p<0.01) with a trend for significance during Nback (p=0.08) compared to baseline. In OA, the %Δ in MAP during N‐back was lower during Indo compared to baseline (p<0.05). Indo had no effect on the %Δ in CVCi (p>0.05). Importantly, there were group differences in the %Δ in MAP during Indo, such that the change was greater in OA compared with YA during Stroop (14.1 ± 1.3% vs. 10.6 ± 1.0%; p<0.05).ConclusionAfter administration of Indo, OA increased MAP to a greater extent during the Stroop test when compared to YA. These results suggest that OA required a larger increase in blood pressure to complete a test of executive function during COX inhibition. Because some COX inhibitors attenuate cerebral blood flow, OA may need to augment blood pressure to complete this metabolically‐challenging task.Support or Funding InformationThis research was funded by NIH grant HL118154.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Unusually large ephedrine-induced blood pressure increases due to cardiac sympathetic denervation supersensitivity in a patient with Parkinson\u2019s disease

BackgroundParkinson’s disease (PD) patients often suffer from cardiac sympathetic denervation, a hallmark of which is orthostatic hypotension. Denervation supersensitivity to sympathomimetic drugs is also seen in such patients, and this phenomenon is important and can be sometimes dangerous.Case presentationA 65-year-old male underwent gastrojejunostomy. The patient had severe PD and did not exhibit metaiodobenzylguanidine (MIBG) accumulation in his heart, which was indicative of cardiac sympathetic nerve denervation. When 8 mg of ephedrine was administered intravenously, an unexpectedly large increase in blood pressure was observed. The phenomenon recurred when 4 mg of ephedrine was administered again, and nicardipine was required to suppress the patient’s blood pressure.ConclusionsDenervation supersensitivity is not as well recognized as other complications seen in PD patients, but anesthesiologists should be aware of it because sympathomimetic drugs can have excessively strong effects in patients with the condition.

A longitudinal study of altered taste and smell perception and change in blood pressure

Background and AimsPrevious studies suggest that olfactory receptors, which mediate smell chemosensation, are located in the kidney and involved in blood pressure regulation. Mammalian epithelial sodium channels located in taste receptor cells are also found to participate in blood pressure regulation. However, there is currently no human study that has examined the association between taste and smell function and blood pressure. We thus conducted a longitudinal study to examine whether participants with altered taste and smell perception had larger increases in blood pressure compared with those without altered perception in a community-based cohort. Methods and ResultsThe study included 5190 Chinese adults (4058 men and 1132 women) who were normotensive at baseline. Taste and smell perception were assessed via questionnaire in 2012 (baseline). Blood pressure was measured in 2012 and 2014 to determine relative change in blood pressure. Mean differences of 2-year blood pressure change and 95% confidence intervals (CIs) across four categories of taste and smell perception were calculated after adjusting for known risk factors for hypertension. After adjusting for potential confounders, individuals with altered taste and smell perception had larger increases in systolic blood pressure (adjusted mean difference = 5.1 mmHg, 95% CI: 0.1–10.0, p-value: 0.04) and mean arterial pressure (adjusted mean difference = 3.8 mmHg, 95% CI: 0.4–7.1, p-value: 0.03) after two years of follow-up compared with those having neither altered taste nor altered smell perception. No significant association was observed in individuals with altered taste or smell perception only. ConclusionOur results suggest an association between chemosensory function and blood pressure.

The Effect of Occupational Lifting on Hypertension Risk: Protocol for a Project Using Data From the Copenhagen City Heart Study.

BackgroundHypertension is a major risk factor for cardiovascular disease and is responsible for 14% of all annual deaths globally. The prevalence of hypertension varies across occupational groups, possibly affected by differences in the working environment. One work-related factor that might impose a risk for hypertension is lifting due to the acute large increases in blood pressure (BP) during lifting.ObjectiveThe aim of this study is to explore associations between heavy occupational lifting and hypertension in the Copenhagen City Heart Study.MethodsThis study will use data from the third, fourth, and fifth examination of the Copenhagen City Heart Study. The dataset contains person-based information on health as well as a large variety of biological, environmental, and lifestyle-related factors. Using a cross-sectional design, we will investigate the association between heavy occupational lifting and hypertension, defined as using antihypertensive drugs or having a measured systolic BP (SBP) ≥140 mm Hg or diastolic BP (DBP) ≥90 mm Hg. Furthermore, in a prospective design, we will investigate the association between heavy occupational lifting and risk of becoming an SBP case, defined as the shift from not using antihypertensive drugs in examination n to use of antihypertensive drugs in examination n+1 or an above median delta value of SBP (SBP in examination n+1−SBP in examination n).ResultsIn the third examination in 1991-1994, 10,135 out of 16,560 participants attended (61.20%), in the fourth examination in 2001-2003, 6237 out of 12,599 participants attended (49.50%), and in the fifth examination in 2011-2015, 4550 out of 9765 participants attended (46.59%). On the basis of the inclusion criteria of answering to the level of occupational physical activity, 5031 observations were excluded from examination 3, 2600 from examination 4, and 1621 from examination 5. Hence, the final populations for the cross-sectional and prospective analysis are assumed to include less than 7166 participants in the cross-sectional analysis and less than 1850 participants in the prospective analysis due to the additional inclusion criteria of measured BP and use of antihypertensive drugs.ConclusionsOne-third of the workforce in Europe reports to carry or move heavy loads regularly during working hours (6th survey in Eurofound). Thus, if this study shows occupational lifting to increase the risk for hypertension, the prevention for hypertension can be improved.

Spot urine protein measurements in normotensive pregnancies, pregnancies with isolated proteinuria and preeclampsia

We performed a prospective, longitudinal study of pregnant women presenting to their first obstetrics visits to characterize the changes in spot urine protein-to-creatinine (UPCR) and albumin-to-creatinine ratios (UACR) in normotensive pregnancies, as well as identify clinical characteristics associated with isolated proteinuria and preeclampsia. We measured spot urinary albumin, protein, and creatinine at the first prenatal visit, end of the second trimester, and at delivery. In the normotensive pregnancies (n = 142), we found that from the beginning of pregnancy to delivery, UACR increased by a median [interquartile range (IQR)] of 14.7 mg/g Cr (3.74-51.8) and UPCR by 60 mg/g Cr (30-130) (P < 0.001 for both changes). Isolated proteinuria (defined as UPCR > 300 mg/g Cr in the absence of hypertension) was identified in 19/142 (13.4%) normotensive pregnancies. Increases in systolic and diastolic blood pressure from early pregnancy to delivery and increases in UACR from early to midpregnancy were associated with isolated proteinuria at delivery. Twelve women developed preeclampsia. Nulliparity, early, and midpregnancy diastolic blood pressures were strongly associated with the development of preeclampsia, but early changes in UACR were not. In conclusion, women who develop isolated proteinuria at delivery have a larger increase in blood pressure than women without proteinuria and have a "microalbuminuric" phase earlier in gestation, unlike women who develop preeclampsia. These findings suggest a different mechanism of urine protein excretion in women with isolated proteinuria as compared with women with preeclampsia, where proteinuria has a more abrupt onset.

Impact of Sex and GPER on the Cardiovascular Effects of the Environmental Estrogen Bisphenol A

We previously found that the membrane‐bound G‐protein coupled estrogen receptor (GPER) attenuates blood pressure. Environmental estrogens, such as Bisphenol A (BPA) compete for binding at GPER, potentially reducing its beneficial vascular effects. Recent clinical data shows that exposure to BPA is associated with higher blood pressure and cardiovascular disease. The goal of the current study was to assess the effects of BPA on blood pressure in a mouse model and determine the impact of sex and GPER. We hypothesized that BPA administration in female mice would induce a larger increase in blood pressure in comparison to males because of its interference with estrogen's protective vascular effects. Further, we hypothesized that the response to BPA in GPER knockout mice would be diminished. Female (f) and Male (m) wild type (WT) and knockout (KO) mice were administered 5 mg/kg body weight/day of BPA via the drinking water for eight weeks. Blood pressures were measured via tail cuff by volume pressure recording biweekly. Two‐way ANOVA revealed a significant effect of sex (P&lt;0.001) but not GPER deletion (P=0.19) on systolic blood pressure, with females having lower pressures (mWT 148 ± 2.8 vs. fWT 131± 4, P&lt;0.01; mKO 142±3 vs. fKO 128± 3, P&lt;0.05). Diastolic pressures were not statistically different by sex (P=0.08) or GPER deletion (P=0.82). Although the study is ongoing, two weeks after the administration of BPA, there was no significant impact of BPA on blood pressure in any group (P&gt;0.05). In conclusion, since GPER mediates some of the beneficial cardiovascular actions of estrogen, environmental estrogens such as Bisphenol A may act as a “hormonal block” of GPER. Increasing amounts of environmental estrogens may promote cardiovascular problems, especially in aging postmenopausal women.Support or Funding InformationTulane University Newcomb College Lurcy GrantAmerican Heart Association 15GRNT25890021

Do Non‐C1 Cells In The Rostral Ventrolateral Medulla Increase Blood Pressure?

C1 cells are a major group of neurons located in the rostral ventrolateral medulla (RVLM) that are glutamatergic and contain catecholamine synthetic enzymes such as tyrosine‐hydroxylase (TH), dopamine‐beta hydroxylase (DBH), and phenylethanolamine N‐methlytransferase (PNMT) (DePuy et al., 2013; Stornetta et al., 2002). Limited amount of information is available that suggests these neurons are the exclusive influence on blood pressure. Non‐C1 catechominergic cells also express vesicular glutamate transporter‐2 (VGLUT2) and are barosensitive and thus may have an impact on blood pressure (Stornetta et al., 2002). Optogenetic activation of C1 cells increases blood pressure specifically targeted in TH‐Cre rats by using a Cre‐dependent vector that drives channelrodopsin‐2 (ChR2) tagged with mCherry (Burke and Guyenet, 2014). However, in the mouse model when C1 cells are stimulated the results indicate a decrease in blood pressure. This difference is perhaps due to the close proximity of different types of C1 cells that are separated in the rat model. When C1 and non‐C1 neurons are stimulated in mice with the use of a CAMKII vector, there is a large increase in blood pressure. One unanswered question is whether CAMKII transduces glutamatergic neurons in the brainstem. This present study uses a CAMKII vector to express ChR2 in combination with mCherry. Oligonucleotide probes were used to label cells positive for VGLUT2. By using light microscopy we will ask if the non‐C1 cells transduced by CAMKII are glutamatergic. We found that on average, 90% (N=3) of CAMKII transduced cells within the RVLM contain VGLUT2.Support or Funding InformationUniversity of Virginia Summer Research Internship Program

The Effect of Nitric Oxide Inhibition in Spinal Cord Injured Humans with and without Preserved Sympathetic Control of the Vasculature.

Systemic pharmacological inhibition of nitric oxide (NO) causes a hypertensive response, which has been attributed both to inhibition of peripheral NO-mediated vasodilatation and to inhibition of central nervous NO-production leading to a later onset sympathetic vasoconstriction. In the present study we aimed to test the importance of these two mechanisms by comparing the time-courses of the hypertensive responses in spinal cord injured (SCI) subjects with varying degrees of loss of sympathetic vascular control depending on level of injury as well as able-bodied controls. We hypothesized that high level SCI with no sympathetic vasoconstrictor control would have an abbreviated time-course of the hypertensive response to the NO-inhibitor L-NAME, because they would lack the late onset sympathetic component to the hypertensive response. NO production was blocked in 12 subjects with SCI and 6 controls by intravenous infusion of L-NAME (1.55–2.7 mg/kg). We measured blood pressure, heart rate, and vascular conductance in the carotid, brachial, and femoral arteries before, during, and after 1 h of L-NAME in a 4-h protocol. Peak increases in mean arterial pressure were significantly larger in high level SCI vs. controls: 32 ± 6 vs. 12 ± 2 mmHg (both groups received 1.55 mg/kg). The decreases in vascular conductance in the brachial and femoral vascular beds were also larger in the high level SCI group, whereas decreases in heart rate and carotid conductance were not significantly different between the groups. There were no indications of any abbreviated responses in blood pressure or vascular conductance in the high level SCI compared to control. The mid level and low-level SCI subject had responses similar to controls. These data confirm previous reports that NO inhibition causes a larger increase in blood pressure in high level SCI, and extend these data by providing evidence for differences in vascular conductance in the limbs. The current data do not support an obligatory important role for sympathetic vasoconstriction in maintaining the hypertensive response to L-NAME in humans.

Large Increase in Blood Pressure After Extubation and High Body Mass Index Elevate the Risk of Spinal Epidural Hematoma After Spinal Surgery.

Matched case-control study. To identify factors other than a multilevel procedure that increase the risk of symptomatic postoperative spinal epidural hematoma (SEH). Postoperative SEH is a potentially devastating complication of spinal surgery. Previous studies that reported risk factors for postoperative SEH all identified a multilevel procedure as a risk factor, but the other risk factors remain unclear. Patients who developed postoperative SEH requiring surgical evacuation were identified from database. Each patient was matched with 3 controls who underwent spinal decompression at the same number of levels in the same part of the spine by the same surgeon during the preceding or following year. Multiple logistic regression analysis was performed to identify the risk factors for postoperative SEH to obtain adjusted odds ratios with 95% confidence intervals. Clinical outcomes after evacuation were investigated separately divided with or without severe paralysis or time until the second surgery. Postoperative SEH evacuation was performed after 32 of 8250 (0.39%) spinal decompression procedures. The incidence was significantly higher after thoracic procedures (2.41%) than after cervical (0.21%) or lumbar (0.39%) procedures. Multivariate analysis identified a 50 mm Hg or greater increase in systolic blood pressure after extubation (adjusted odds ratio: 3.22, 95% confidence interval: 1.22-8.51) and higher body mass index (adjusted odds ratio 1.15, 95% confidence interval: 1.01-1.31) as risk factors. Among 14 patients with severe paralysis due to postoperative SEH, those who underwent evacuation within 24 hours of the onset had a significantly better improvement in clinical outcome and Frankel grade than did those after 24 hours. A 50 mm Hg or greater increase in systolic blood pressure after extubation and high body mass index were identified as risk factors for SEH. Appropriate blood pressure control especially at the end of surgery is important for the prevention of postoperative SEH, particularly in obese patients. 3.

H2S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

Context. Hydrogen sulfide (H2S) intoxication produces an acute depression in cardiac contractility-induced circulatory failure, which has been shown to be one of the major contributors to the lethality of H2S intoxication or to the neurological sequelae in surviving animals. Methylene blue (MB), a phenothiazinium dye, can antagonize the effects of the inhibition of mitochondrial electron transport chain, a major effect of H2S toxicity. Objectives. We investigated whether MB could affect the immediate outcome of H2S-induced coma in un-anesthetized animals. Second, we sought to characterize the acute cardiovascular effects of MB and two of its demethylated metabolites—azure B and thionine—in anesthetized rats during lethal infusion of H2S. Materials and methods. First, MB (4 mg/kg, intravenous [IV]) was administered in non-sedated rats during the phase of agonal breathing, following NaHS (20 mg/kg, IP)-induced coma. Second, in 4 groups of urethane-anesthetized rats, NaHS was infused at a rate lethal within 10 min (0.8 mg/min, IV). Whenever cardiac output (CO) reached 40% of its baseline volume, MB, azure B, thionine, or saline were injected, while sulfide infusion was maintained until cardiac arrest occurred. Results. Seventy-five percent of the comatose rats that received saline (n = 8) died within 7 min, while all the 7 rats that were given MB survived (p = 0.007). In the anesthetized rats, arterial, left ventricular pressures and CO decreased during NaHS infusion, leading to a pulseless electrical activity within 530 s. MB produced a significant increase in CO and dP/dtmax for about 2 min. A similar effect was produced when MB was also injected in the pre-mortem phase of sulfide exposure, significantly increasing survival time. Azure B produced an even larger increase in blood pressure than MB, while thionine had no effect. Conclusion. MB can counteract NaHS-induced acute cardiogenic shock; this effect is also produced by azure B, but not by thionine, suggesting that the presence of methyl groups is a prerequisite for producing this protective effect.

Endothelin ETB receptors contribute to sex differences in blood pressure elevation in angiotensin II hypertensive rats on a high‐salt diet

Female rats are more resistant to blood pressure increases induced by high salt (HS) intake or angiotensin (Ang) II infusion. Because endothelin ET(B) receptors on endothelial and epithelial cells mediate tonic vasodilation and sodium excretion, we hypothesized that ET(B) receptors limit the hypertensive response and renal injury induced by HS diet alone or with chronic AngII infusion (AngII/HS) in female compared with male rats. A 4 week HS diet (4% NaCl) did not significantly change blood pressure (measured by telemetry) in either male or female Sprague-Dawley rats. Administration of the ET(B) receptor antagonist A-192621 (1, 3 and 10 mg/kg per day in food) during HS feeding caused a dose-dependent increase in blood pressure in both sexes. In AngII/HS rats, males had a larger increase in blood pressure than females. The increase in blood pressure produced by ET(B) receptor blockade in male AngII/HS rats was not significant. However, A-192621 treatment resulted in a significant further increase in blood pressure in female AngII/HS rats. Male rats had consistently higher protein excretion rates before and during AngII/HS, but this was not significantly affected by ET(B) receptor blockade in either sex. In conclusion, ET(B) receptors play a significantly greater beneficial role in protecting female compared with male rats against AngII-induced hypertension and may contribute to the sex differences in AngII-induced hypertension.