Sympathetic determinants of resting blood pressure in males and females.

Discharge of postganglionic muscle sympathetic nerve activity (MSNA) is related poorly to blood pressure (BP) in adults. Whether neural measurements beyond the prevailing level of MSNA can account for interindividual differences in BP remains unclear. The current study sought to evaluate the relative contributions of sympathetic-BP transduction and sympathetic baroreflex gain on resting BP in young adults. Data were analyzed from 191 (77 females) young adults (18-39 years) who underwent continuous measurement of beat-to-beat BP (finger photoplethysmography), heart rate (electrocardiography), and fibular nerve MSNA (microneurography). Linear regression analyses were computed to determine associations between sympathetic-BP transduction (signal-averaging) or sympathetic baroreflex gain (threshold technique) and resting BP, before and after controlling for age, body mass index, and MSNA burst frequency. K-mean clustering was used to explore sympathetic phenotypes of BP control and consequential influence on resting BP. Sympathetic-BP transduction was unrelated to BP in males or females (both R2 < 0.01; P > 0.67). Sympathetic baroreflex gain was positively associated with BP in males (R2 = 0.09, P < 0.01), but not in females (R2 < 0.01; P = 0.80), before and after controlling for age, body mass index, and MSNA burst frequency. K-means clustering identified a subset of participants with average resting MSNA, yet lower sympathetic-BP transduction and lower sympathetic baroreflex gain. This distinct subgroup presented with elevated BP in males (P < 0.02), but not in females (P = 0.10). Sympathetic-BP transduction is unrelated to resting BP, while the association between sympathetic baroreflex gain and resting BP in males reveals important sex differences in the sympathetic determination of resting BP.NEW & NOTEWORTHY In a sample of 191 normotensive young adults, we confirm that resting muscle sympathetic nerve activity is a poor predictor of resting blood pressure and now demonstrate that sympathetic baroreflex gain is associated with resting blood pressure in males but not females. In contrast, signal-averaged measures of sympathetic-blood pressure transduction are unrelated to resting blood pressure. These findings highlight sex differences in the neural regulation of blood pressure.

Guidelines on the use of sex and gender in cardiovascular research.

In cardiovascular research, sex and gender have not typically been considered in research design and reporting until recently. This has resulted in clinical research findings from which not only all women, but also gender-diverse individuals have been excluded. The resulting dearth of data has led to a lack of sex- and gender-specific clinical guidelines and raises serious questions about evidence-based care. Basic research has also excluded considerations of sex. Including sex and/or gender as research variables not only has the potential to improve the health of society overall now, but it also provides a foundation of knowledge on which to build future advances. The goal of this guidelines article is to provide advice on best practices to include sex and gender considerations in study design, as well as data collection, analysis, and interpretation to optimally establish rigor and reproducibility needed to inform clinical decision-making and improve outcomes. In cardiovascular physiology, incorporating sex and gender is a necessary component when optimally designing and executing research plans. The guidelines serve as the first guidance on how to include sex and gender in cardiovascular research. We provide here a beginning path toward achieving this goal and improve the ability of the research community to interpret results through a sex and gender lens to enable comparison across studies and laboratories, resulting in better health for all.

Autonomic control of cerebral blood flow: fundamental comparisons between peripheral and cerebrovascular circulations in humans.

Understanding the contribution of the autonomic nervous system to cerebral blood flow (CBF) control is challenging, and interpretations are unclear. The identification of calcium channels and adrenoreceptors within cerebral vessels has led to common misconceptions that the function of these receptors and actions mirror those of the peripheral vasculature. This review outlines the fundamental differences and complex actions of cerebral autonomic activation compared with the peripheral circulation. Anatomical differences, including the closed nature of the cerebrovasculature, and differential adrenoreceptor subtypes, density, distribution and sensitivity, provide evidence that measures on peripheral sympathetic nerve activity cannot be extrapolated to the cerebrovasculature. Cerebral sympathetic nerve activity seems to act opposingly to the peripheral circulation, mediated at least in part by changes in intracranial pressure and cerebral blood volume. Additionally, heterogeneity in cerebral adrenoreceptor distribution highlights region-specific autonomic regulation of CBF. Compensatory chemo- and autoregulatory responses throughout the cerebral circulation, and interactions with parasympathetic nerve activity are unique features to the cerebral circulation. This crosstalk between sympathetic and parasympathetic reflexes acts to ensure adequate perfusion of CBF to rising and falling perfusion pressures, optimizing delivery of oxygen and nutrients to the brain, while attempting to maintain blood volume and intracranial pressure. Herein, we highlight the distinct similarities and differences between autonomic control of cerebral and peripheral blood flow, and the regional specificity of sympathetic and parasympathetic regulation within the cerebrovasculature. Future research directions are outlined with the goal to further our understanding of autonomic control of CBF in humans.

Near-Room-Temperature Magnetoelectric Coupling via Spin Crossover in an Iron(II) Complex.

Magnetoelectric coupling is achieved near room temperature in a spin crossover FeII molecule-based compound, [Fe(1bpp)2 ](BF4 )2 . Large atomic displacements resulting from Jahn-Teller distortions induce a change in the molecule dipole moment when switching between high-spin and low-spin states leading to a step-wise change in the electric polarization and dielectric constant. For temperatures in the region of bistability, the changes in magnetic and electrical properties are induced with a remarkably low magnetic field of 3 T. This result represents a successful expansion of magnetoelectric spin crossovers towards ambient conditions. Moreover, the observed 0.3-0.4 mC m-2 changes in the H-induced electric polarization suggest that the high strength of the coupling obtained via this route is accessible not just at cryogenic temperatures but also near room temperature, a feature that is especially appealing in the light of practical applications.

Sex differences in vascular transduction of sympathetic nerve activity.

PURPOSE: Sympathetic vasoconstriction plays a major role in the beat-to-beat control of blood pressure. To be effective and thus avoid dangerously high or low blood pressures, this mechanism relies upon transduction of sympathetic nerve activity at the level of the vasculature. However, recent evidence suggests that considerable variability exists in beat-to-beat vascular transduction, particularly between the sexes. METHODS: We reviewed the methods available for quantifying beat-to-beat transduction of muscle sympathetic nerve activity (MSNA) and explored the recent evidence for sex differences in vascular transduction. We paid specific attention to relationships between vascular transduction and factors such as resting levels of sympathetic nerve activity and baroreflex sensitivity. RESULTS: There are two dominant methods now available for the quantification of beat-to-beat transduction of muscle sympathetic nerve activity at rest. Whilst there is some evidence to suggest that young females exhibit lower levels of vascular transduction, results vary depending on the method used and the direction of change in MSNA. Evidence suggests that compensatory relationships may exist between key components of neurovascular control, such as vascular transduction and resting levels of MSNA. Also consistent is the presence of such relationships in young males but not young females. CONCLUSION: The lack of significant relationships in young females may reflect the influence of vasodilator mechanisms that counteract sympathetic vasoconstriction. The assessment of vascular transduction following MSNA bursts and non-bursts in males and females, both young and older, may help to gain a mechanistic understanding of the prevalence of hypotensive and hypertensive disorders across the lifespan.

Central command increases muscle sympathetic nerve activity more to contracting than noncontracting muscle during rhythmic isotonic leg exercise.

We have previously shown that the increase in muscle sympathetic nerve activity (MSNA) to contracting muscle during sustained isometric exercise is due primarily to central command and that contracting muscle does not express a metaboreceptor-driven increase in MSNA. Here we tested the hypothesis that MSNA increases to the contracting muscle also during rhythmic isotonic exercise, in which muscle metabolites will not accumulate because the contraction is performed without external load. MSNA was recorded from the common peroneal nerve in 10 participants, and negative-going sympathetic spikes were extracted during 50 cycles of sinusoidal (0.15 Hz) isotonic dorsiflexions of the ipsilateral or contralateral ankle. Electromyographic activity (EMG) was recorded from the tibialis anterior muscle on both sides. Cross-correlation analysis between MSNA and EMG revealed a marked cyclic modulation of MSNA to the contracting (ipsilateral) muscle. This modulation, in which MSNA increased during the contraction phase, was three times greater than that to the noncontracting muscle (modulation index = 27.4 ± 3.2% vs. 9.2 ± 1.5%; P < 0.002). There were no differences in either the intensity or the magnitude of modulation of EMG during ipsilateral and contralateral contractions. We conclude that central command increases MSNA to the contracting muscle during rhythmic isotonic exercise. NEW & NOTEWORTHY Muscle sympathetic nerve activity (MSNA) increases to contracting muscle during isometric exercise, but whether this occurs during rhythmic isotonic exercise is unknown. We recorded MSNA to the pretibial flexors during cyclic dorsiflexion of the ipsilateral or contralateral ankle. MSNA showed a cyclic increase during the contraction phase that was significantly higher to the contracting than the noncontracting muscle, supporting central command as the primary mechanism responsible for increasing MSNA.

Sympathetic baroreflex sensitivity is inversely related to vascular transduction in men but not women.

Sympathetic baroreflex sensitivity (BRS) is a measure of how effectively the baroreflex buffers beat-to-beat changes in blood pressure through the modulation of muscle sympathetic nerve activity (MSNA). However, current methods of assessment do not take into account the transduction of sympathetic nerve activity at the level of the vasculature, which is known to vary between individuals. In this study we tested the hypothesis that there is an inverse relationship between sympathetic BRS and vascular transduction. In 38 (18 men) healthy adults, continuous measurements of blood pressure, MSNA and superficial femoral artery diameter and blood flow (Doppler ultrasound) were recorded during 10 min of rest. Spontaneous sympathetic BRS was quantified as the relationship between diastolic pressure and MSNA burst incidence. Vascular transduction was quantified by plotting the changes in leg vascular conductance for 10 cardiac cycles following each burst of MSNA, and taking the nadir. In men, sympathetic BRS was inversely related to vascular transduction (r = -0.49; P = 0.04). However, this relationship was not present in women (r = -0.17; P = 0.47). To conclude, an interaction exists between sympathetic BRS and vascular transduction in healthy men, such that men with high sympathetic BRS have low vascular transduction and vice versa. This may be to ensure that blood pressure is regulated effectively, although further research is needed to explore what mechanisms are involved and examine why this relationship was not apparent in women.NEW & NOTEWORTHY Evidence suggests that compensatory interactions exist between factors involved in cardiovascular control. This study was the first to demonstrate an inverse relationship between sympathetic BRS and beat-to-beat vascular transduction. Those with low sympathetic BRS had high vascular transduction and vice versa. However, this interaction was present in young men but not women.

The metaboreflex does not contribute to the increase in muscle sympathetic nerve activity to contracting muscle during static exercise in humans.

KEY POINTS: It is not clear how sympathetic activity to contracting muscle is controlled. We recorded muscle sympathetic nerve activity (MSNA) to the ipsilateral tibialis anterior muscle during 4 min of isometric dorsiflexion of the ankle and 6 min of post-exercise ischaemia, which was repeated contralaterally. MSNA to the contracting muscle increased within 1 min of static exercise and returned to pre-contraction levels at the end. Unlike the increase in MSNA seen in the non-contracting muscle, post-exercise ischaemia had no effect on MSNA to the contracted muscle. We conclude that central command is the primary mechanism responsible for increasing MSNA to contracting muscle and also that the metaboreflex is not expressed in contracting muscle. ABSTRACT: Both central command and metaboreflex inputs from contracting muscles increase muscle sympathetic nerve activity (MSNA) to non-contracting muscle during sustained isometric exercise. We recently showed that MSNA to contracting muscle also increases in an intensity-dependent manner, although whether this can be sustained by the metaboreflex is unknown. MSNA was recorded from the left common peroneal nerve and individual spikes of MSNA extracted from the nerve signal. Eleven subjects performed a series of 4 min dorsiflexions of the left ankle at 10% of maximum voluntary contraction under three conditions: without ischaemia, with 6 min of post-exercise ischaemia, and with ischaemia during and after exercise; these were repeated in the right leg. Compared with pre-contraction values, MSNA to the contracting muscles increased and plateaued in the first minute of contraction (50 ± 18 vs. 34 ± 10 spikes min-1 , P = 0.01), returned to pre-contraction levels within 1 min of the contraction ending and was not influenced by ischaemia during or after contraction. Conversely, MSNA to the non-contracting muscles was not different from pre-contraction levels in the first minute of contraction (34 ± 9 vs. 32 ± 5 spikes min-1 , P = 0.48), whereas it increased each minute and was significantly greater by the second minute (44 ± 8 spikes min-1 , P = 0.01). Ischaemia augmented the MSNA response to contraction (63 ± 25 spikes min-1 after 4 min, P < 0.05) and post-exercise ischaemia (63 ± 27 spikes min-1 after 6 min, P < 0.01) for the non-contracting muscles only. These findings support our conclusion that the metaboreflex is not expressed in the contracting muscle during sustained static exercise.

Muscle sympathetic nerve activity peaks in the first trimester in healthy pregnancy: a longitudinal case study.

OBJECTIVE AND METHODS: Muscle sympathetic nerve activity and baroreflex sensitivity were examined at rest before, during (weeks 6, 11, 17, 22, 25, 33 and 36) and after a normotensive pregnancy. RESULTS: Muscle sympathetic nerve activity is elevated during pregnancy with a large peak in the first trimester (Δ17 bursts/min) and a secondary peak in the third trimester (Δ11 bursts/min). Cardiac baroreflex sensitivity peaked in the first trimester (10 vs. 6 ms/mmHg pre-pregnancy), whereas sympathetic baroreflex sensitivity was greater throughout. INTERPRETATION: The increase in sympathetic outflow early in pregnancy cannot be explained by a reduction in baroreflex sensitivity, while the secondary increase in burst frequency in the third trimester may, in part, be explained by the elevated heart rate.

Rate of rise in diastolic blood pressure influences vascular sympathetic response to mental stress.

KEY POINTS: Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress. In this study, we examined the early blood pressure responses (including the peak, time of peak and rate of rise in blood pressure) to mental stress in positive and negative responders. Negative MSNA responders to mental stress exhibit a more rapid rise in diastolic pressure at the onset of the stressor, suggesting a baroreflex-mediated suppression of MSNA. In positive responders there is a more sluggish rise in blood pressure during mental stress, which appears to be MSNA-driven. This study suggests that whether MSNA has a role in the pressor response is dependent upon the reactivity of blood pressure early in the task. ABSTRACT: Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress. The aim was to examine the early blood pressure response to stress in positive and negative responders and thus its influence on the direction of change in MSNA. Blood pressure and MSNA were recorded continuously in 21 healthy young males during 2 min mental stressors (mental arithmetic, Stroop test) and physical stressors (cold pressor, handgrip exercise, post-exercise ischaemia). Participants were classified as negative or positive responders according to the direction of the mean change in MSNA during the stressor tasks. The peak changes, time of peak and rate of changes in blood pressure were compared between groups. During mental arithmetic negative responders experienced a significantly greater rate of rise in diastolic blood pressure in the first minute of the task (1.3 ± 0.5 mmHg s-1 ) compared with positive responders (0.4 ± 0.1 mmHg s-1 ; P = 0.03). Similar results were found for the Stroop test. Physical tasks elicited robust parallel increases in blood pressure and MSNA across participants. It is concluded that negative MSNA responders to mental stress exhibit a more rapid rise in diastolic pressure at the onset of the stressor, suggesting a baroreflex-mediated suppression of MSNA. In positive responders there is a more sluggish rise in blood pressure during mental stress, which appears to be MSNA-driven. This study suggests that whether MSNA has a role in the pressor response is dependent upon the reactivity of blood pressure early in the task.

Blood pressure regulation VII. The "morning surge" in blood pressure: measurement issues and clinical significance.

In keeping with this review-series theme, we question whether the morning surge in blood pressure (MSBP) is a benign response to the physiological challenges during the first 3 h after waking, or is it clinically important? Therefore, we scrutinise the circadian-related mechanisms, the measurement methods and the prognostic value of the MSBP. The MSBP is relatively small (<2 mmHg) under constant routine conditions. Nevertheless, the blood pressure response to exercise can be 8-14 mm Hg greater in the morning vs. afternoon, even when prior sleep is controlled. Systematic bias between MSBP methods can be >10 mmHg. The "sleep-trough" method provides the largest MSBP (≈25 mmHg), but the sensitivity of MSBP to a treatment/intervention depends largely on its repeatability. The repeatability standard deviation (SD) for most MSBP methods is ≈8 mm Hg. While the magnitude of this SD precludes the use of MSBP for diagnostic decisions on individual patients, sample sizes for future intervention studies may be feasible, depending on the minimal clinically important difference in MSBP. This difference is somewhat unclear given that a large MSBP has recently been reported to predict a reduced, rather than a higher, risk of cardiovascular disease, although this particular study has been criticised. The MSBP is also naturally correlated to changes in physical activity and nocturnal "dipping" status. Therefore, it is important to account for these potential confounders of the MSBP, so that more precise knowledge about its clinical significance is gained, thereby providing a sound rationale for physiological investigation and translational research.

Managing misuse of novel psychoactive substances.

Misuse of novel psychoactive substances, also known as legal highs, is growing in the UK. These substances include more than 200 psychoactive chemicals and are associated with harm to physical and mental health, but are not controlled under the Misuse of Drugs Act 1971 or regulated as a medicine. This article reviews the evidence relating to psychosocial interventions for illegal substance misuse to identify how therapies could improve rates of abstinence and awareness in adults who are misusing novel psychoactive substances. The evidence is limited and there is a need for further research and increased awareness among health professionals and the general population of this growing problem.

Limb-specific muscle sympathetic nerve activity responses to the cold pressor test.

Recent studies have demonstrated that muscle sympathetic nerve activity (MSNA) responses to isometric exercise differs between active and inactive limbs. Whether limb-dependent responses are characteristic of responses to the cold pressor test (CPT) remains to be established. Therefore, we tested the hypothesis that CPT-induced MSNA responses differ between affected and unaffected limbs such that MSNA in the affected lower limb is greater than MSNA responses in the contralateral lower limb and the upper limb. Integrated peroneal MSNA (microneurography) was measured in young healthy individuals (n = 10) at rest and during three separate 3-min CPTs: the microneurography foot, opposite foot, and opposite hand. Peak MSNA responses were extracted for further analysis, as well as corresponding hemodynamic outcomes including mean arterial pressure (MAP; Finometer). MSNA responses were greater when the microneurography foot was immersed in ice water than when the opposite foot was immersed (38 ± 18 vs 28 ± 16 bursts/100hb: P < 0.01). MSNA responses when the opposite hand was immersed were greater than both the microneurography foot (46 ± 22 vs 38 ± 18 bursts/100hb: P < 0.01) and opposite foot (46 ± 22 vs 28 ± 16 bursts/100hb: P ≤0.01). Likewise, MAP responses were greater during the hand CPT than the microneurography foot (99 ± 9 vs 96 ± 8 mmHg: P < 0.01) and opposite foot CPT (99 ± 9 vs 96 ± 9 mmHg: P < 0.01). These data indicate that (a) upper limbs and (b) immersed limbs elicit greater MSNA responses to the CPT than lower and/or non-immersed limbs.

Maintained cerebrovascular function during post-exercise hypotension.

The post-exercise period is associated with hypotension, and an increased risk of syncope attributed to decreases in venous return and/or vascular resistance. Increased local and systemic vasodilators, sympatholysis, and attenuated baroreflex sensitivity following exercise are also manifest. Although resting cerebral blood flow is maintained, cerebrovascular regulation to acute decreases in blood pressure has not been characterized following exercise. We therefore aimed to assess cerebrovascular regulation during transient bouts of hypotension, before and after 40 min of aerobic exercise at 60 % of estimated maximum oxygen consumption. Beat to beat blood pressure (Finometer), heart rate (ECG), and blood velocity in the middle cerebral artery (MCAv; transcranial Doppler ultrasound) were assessed in ten healthy young humans. The MCAv-mean arterial pressure relationship during a pharmacologically (i.v. sodium nitroprusside) induced transient hypotension was assessed before and at 10, 30, and 60 min following exercise. Despite a significant reduction in mean arterial pressure at 10 min post-exercise (-10 ± 6.9 mmHg; P < 0.05) and end-tidal PCO2 (10 min post: -2.9 ± 2.6 mmHg; 30 min post: -3.9 ± 3.5 mmHg; 60 min post: -2.7 ± 2.0 mmHg; all P < 0.05), neither resting MCAv nor the cerebrovascular response to hypotension differed between pre- and post-exercise periods (P > 0.05). These data indicate that cerebrovascular regulation remains intact following a moderate bout of aerobic exercise.

Using Comprehensive Geriatric Assessment in Identifying Care Goals and Referral Services in a Frailty Intervention Clinic.

The proportion of older adults and frail adults in Canada is expected to rise significantly in upcoming years. Currently, a considerable number of older adults do not actively participate in developing their own care plans; prior research has indicated several benefits of patient engagement in this process. Thus, we conducted a mixed methods study that examined the prevalence of rehabilitation goals and identified these for 305 community dwelling older adults referred to a frailty intervention clinic utilizing Comprehensive Geriatric Assessment (CGA) between 2014 and 2018. Top patient concerns included mobility (84%), services, systems, and policies (51%), sensory functions and pain (50%), and self-care or domestic life (47%). The most common referrals or recommendations for patients included further follow-up with a physician or specialist (36%), referral to an onsite falls prevention clinic (31%), and medication modifications (31%). Based upon these findings, we recommend greater utilization of CGA within a team-based approach to improve patient care by allowing for greater collaboration and shared decision-making by health-care providers. Moreover, CGA can be an effective tool to meet the complex and unique health-care needs of frail patients while incorporating patient goals. This is vitally important considering the predicted growth in the population of frail and/or older patients, as well as the current challenges and shortfalls in meeting the health-care needs of this population.

Effect of gas composition during Pt sputtering on structural and magnetic properties of CoFeB thin films.

Ultrathin Ta/CoFeB/Pt trilayer structures are relevant to a wide range of spintronic applications, from magnetic tunnel junctions to skyrmionics devices. Controlling the perpendicular magnetic anisotropy, Gilbert damping and Dzyaloshinskii-Moriya interaction in the CoFeB layer is key for these applications. We examine the role of sputter gas composition during the Pt overlayer deposition of a Ta/CoFeB/Pt trilayer in Ar, Kr and Xe working gas environments during direct current magnetron sputtering. Decreasing density of the Pt layer (from 21 g/cm3 to 15 g/cm3) was apparent in specular x-ray reflectivity measurements of the trilayer films when increasing the molecular weight of the sputtering gas from Ar to Kr to Xe. Significant effects on the Gilbert damping and the interfacial Dzyaloshinskii-Moriya interaction (DMI) energy were observed, with increases in the damping from 0.037(1) to 0.042(1) to 0.048(1), and reductions in the interfacial DMI from 0.47(4) mJ/m2 to 0.45(5) mJ/m2 to 0.39(4) mJ/m2. The ability to control the perpendicular magnetization and DMI strength of these materials through judicious interfacial control is a means toward magnetic devices with better stability at smaller lateral dimension, key to device scaling for spintronic device arrays.