Aging and sympathetic transduction to blood pressure in humans: methodological and physiological considerations.

Recent reports suggest that quantification of signal-averaged sympathetic transduction is influenced by resting muscle sympathetic nerve activity (MSNA) and burst occurrence relative to the average mean arterial pressure (MAP). Herein, we asked how these findings may influence age-related reductions in sympathetic transduction. Beat-to-beat blood pressure and MSNA were recorded during 5 min of rest in 27 younger (13 females: age, 25 ± 5 yr; BMI, 25 ± 4 kg/m2) and 26 older (15 females: age, 59 ± 5 yr; BMI, 26 ± 4 kg/m2) healthy adults. All MSNA bursts were signal averaged together. Beat-to-beat MAP values were then split into low (T1), middle (T2), and high (T3) tertiles, and signal-averaged transduction was calculated within each tertile. Resting MSNA was higher in older adults and MAP was similar between groups. Older adults exhibited blunted overall MAP transduction (younger, Δ1.5 ± 0.6 vs. older, Δ0.9 ± 0.7 mmHg; P = 0.005), which was irrespective of relation to prevailing MAP. A greater proportion of bursts occurred above the average MAP in older adults (P < 0.001), and a larger proportion of these bursts were associated with depressor responses (P = 0.005). Nonetheless, assessment of bursts above the average MAP associated with pressor responses revealed similar age-associated reductions in transduction (younger, Δ2.6 ± 1.6 vs. older, Δ1.7 ± 0.8 mmHg; P = 0.016). These findings indicate an age-related increase in burst occurrence above the average resting MAP, which alone does not explain blunted transduction, thereby supporting the physiological underpinnings of age-related decrements in sympathetic transduction to blood pressure.NEW & NOTEWORTHY The current study demonstrated that aging is associated with a greater prevalence of sympathetic bursts occurring above the average blood pressure, which offers both methodologically and physiologically relevant information regarding aging and sympathetic control of blood pressure. These data support age-related reductions in sympathetic transduction via a reduced pressor response to sympathetic bursts irrespective of the prevailing absolute blood pressure value, along with increases in sympathetic outflow necessary to maintain blood pressure.

Sex as a biological variable for cardiovascular physiology.

There have been ongoing efforts by federal agencies and scientific communities since the early 1990s to incorporate sex and/or gender in all aspects of cardiovascular research. Scientific journals provide a critical function as change agents to influence transformation by encouraging submissions for topic areas, and by setting standards and expectations for articles submitted to the journal. As part of ongoing efforts to advance sex and gender in cardiovascular physiology research, the American Journal of Physiology-Heart and Circulatory Physiology recently launched a call for papers on Considering Sex as a Biological Variable. This call was an overwhelming success, resulting in 78 articles published in this collection. This review summarizes the major themes of the collection, including Sex as a Biological Variable Within: Endothelial Cell and Vascular Physiology, Cardiovascular Immunity and Inflammation, Metabolism and Mitochondrial Energy, Extracellular Matrix Turnover and Fibrosis, Neurohormonal Signaling, and Cardiovascular Clinical and Epidemiology Assessments. Several articles also focused on establishing rigor and reproducibility of key physiological measurements involved in cardiovascular health and disease, as well as recommendations and considerations for study design. Combined, these articles summarize our current understanding of sex and gender influences on cardiovascular physiology and pathophysiology and provide insight into future directions needed to further expand our knowledge.

Sleep disturbance and sympathetic neural reactivity in postmenopausal females.

Sleep disturbance, one of the most common menopausal symptoms, contributes to autonomic dysfunction and is linked to hypertension and cardiovascular risk. Longitudinal studies suggest that hyperreactivity of blood pressure (BP) to a stressor can predict the future development of hypertension. It remains unknown if postmenopausal females who experience sleep disturbance (SDG) demonstrate greater hemodynamic and sympathetic neural hyperreactivity to a stressor. We hypothesized that postmenopausal females with reported sleep disturbance would exhibit increased hemodynamic and sympathetic reactivity to a stressor compared with postmenopausal females without sleep disturbance (non-SDG). Fifty-five postmenopausal females (age, 62 ± 4 yr old; SDG, n = 36; non-SDG; n = 19) completed two study visits. The Menopause-Specific Quality of Life Questionnaire (MENQOL) was used to assess the presence of sleep disturbance (MENQOL sleep scale, ≥2 units). Beat-to-beat BP (finger plethysmography), heart rate (HR; electrocardiogram), and muscle sympathetic nerve activity (MSNA; microneurography; SDG, n = 25; non-SDG, n = 15) were continuously measured during a 10-min baseline and 2-min stressor (cold pressor test; CPT) in both groups. Menopause age and body mass index were similar between groups (P > 0.05). There were no differences between resting BP, HR, or MSNA (P > 0.05). HR and BP reactivity were not different between SDG and non-SDG (P > 0.05). In contrast, MSNA reactivity had a more rapid increase in the first 30 s of the CPT in the SDG (burst incidence, Δ10.2 ± 14.8 bursts/100 hb) compared with the non-SDG (burst incidence, Δ4.0 ± 14.8 bursts/100 hb, time × group, P = 0.011). Our results demonstrate a more rapid sympathetic neural reactivity to a CPT in postmenopausal females with perceived sleep disturbance, a finding that aligns with and advances recent evidence that sleep disturbance is associated with sympathetic neural hyperactivity in postmenopausal females.NEW & NOTEWORTHY This is the first study to demonstrate that muscle sympathetic nerve activity (MSNA) to a cold pressor test is augmented in postmenopausal females with perceived sleep disturbance. The more rapid increase in MSNA reactivity during the cold pressor test in the sleep disturbance group was present despite similar increases in the perceived pain levels between groups. Baseline MSNA burst incidence and burst frequency, as well as blood pressure and heart rate, were similar between the sleep disturbance and nonsleep disturbance groups.

Actigraphy-based sleep and muscle sympathetic nerve activity in humans.

Short and insufficient sleep are prevalent and associated with cardiovascular disease, with the sympathetic nervous system as a suspected mediator. The purpose of the present study was to investigate the association between objective, actigraphy-based total sleep time (TST), sleep efficiency (SE), and cardiovascular and sympathetic regulation in healthy adults. We hypothesized that short TST and low SE would be associated with elevated resting blood pressure, heart rate (HR), and muscle sympathetic nerve activity (MSNA). Participants included 94 individuals [46 males, 48 females, age: 30 ± 15 yr, body mass index (BMI): 26 ± 4 kg/m2]. All participants underwent at least 7 days of at-home, wristwatch actigraphy monitoring (avg: 10 ± 3 days). Seated blood pressures were assessed using brachial blood pressure measurements, followed by a 10-minute supine autonomic testing session consisting of continuous HR (electrocardiogram), beat-by-beat blood pressure (finger plethysmograph), and MSNA (microneurography) monitoring. Partial correlations were used to determine the relationship between sleep and cardiovascular parameters while accounting for the influence of age, sex, and BMI. TST was not associated with MAP (R = -0.105, P = 0.321), HR (R = 0.093, P = 0.383), or MSNA burst frequency (BF; R = -0.168, P = 0.112) and burst incidence (BI; R = -0.162, P = 0.124). Similarly, SE was not associated with MAP (R = -0.088, P = 0.408), HR (R = -0.118, P = 0.263), MSNA BF (R = 0.038, P = 0.723), or MSNA BI (R = 0.079, P = 0.459). In contrast to recent preliminary findings, our results do not support a significant association between actigraphy-based sleep duration or efficiency and measures of resting blood pressure, heart rate, and MSNA.NEW & NOTEWORTHY The present study investigated the independent association between actigraphy-based sleep duration, efficiency, and measures of blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) in adult males and females. Contrary to our hypothesis, the findings do not support an independent association between habitual sleep and cardiovascular or sympathetic neural activity. However, these findings do not preclude a potential association between these parameters in populations with sleep disorders and/or cardiovascular disease.

Binge Alcohol Consumption Elevates Sympathetic Transduction to Blood Pressure: A Randomized Controlled Trial.

BACKGROUND: Alcohol consumption is associated with cardiovascular disease, and the sympathetic nervous system is a suspected mediator. The present study investigated sympathetic transduction of muscle sympathetic nerve activity to blood pressure at rest and in response to cold pressor test following evening binge alcohol or fluid control, with the hypothesis that sympathetic transduction would be elevated the morning after binge alcohol consumption. METHODS: Using a randomized, fluid-controlled (FC) crossover design, 26 healthy adults (12 male, 14 female, 25±6 years, 27±4 kg/m2) received an evening binge alcohol dose and a FC. All participants underwent next-morning autonomic-cardiovascular testing consisting of muscle sympathetic nerve activity, beat-to-beat blood pressure, and heart rate during a 10-minute rest period and a 2-minute cold pressor test. Sympathetic transduction was assessed at rest and during the cold pressor test in both experimental conditions. RESULTS: Evening alcohol increased heart rate (FC: 60±9 versus alcohol: 64±9 bpm; P=0.010) but did not alter resting mean arterial pressure (FC: 80±6 versus alcohol: 80±7 mm Hg; P=0.857) or muscle sympathetic nerve activity (FC: 18±9 versus alcohol: 20±8 bursts/min; P=0.283). Sympathetic transduction to mean arterial pressure (time×condition; P=0.003), diastolic blood pressure (time×condition; P=0.010), and total vascular conductance (time×condition; P=0.004) was augmented after alcohol at rest. Sympathetic transduction during the cold pressor test was also elevated after evening binge alcohol consumption (P=0.002). CONCLUSIONS: These findings suggest that evening binge alcohol consumption leads to augmented morning-after sympathetic transduction of muscle sympathetic nerve activity to blood pressure, highlighting a new mechanism whereby chronic or excessive alcohol consumption contributes to cardiovascular disease progression via altered end-organ responsiveness to sympathetic neural outflow. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03567434.

Blunted brachial blood flow velocity response to acute mental stress in PTSD females.

Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular disease (CVD) risk. Compared with males, females are twice as likely to develop PTSD after trauma exposure, and cardiovascular reactivity to stress is a known risk factor for CVD. We aimed to examine hemodynamic responses to acute mental stress in trauma-exposed females with and without a clinical diagnosis of PTSD. We hypothesized that females with PTSD would have higher heart rate (HR), blood pressure (BP), and lower blood flow velocity (BFV) responsiveness compared with controls. We enrolled 21 females with PTSD and 21 trauma-exposed controls. We continuously measured HR using a three-lead electrocardiogram, BP using finger plethysmography, and brachial BFV using Doppler ultrasound. All variables were recorded during 10 min of supine rest, 5 min of mental arithmetic, and 5 min of recovery. Females with PTSD were older, and had higher BMI and higher resting diastolic BP. Accordingly, age, BMI, and diastolic BP were covariates for all repeated measures analyses. Females with PTSD had a blunted brachial BFV response to mental stress (time × group, p = 0.005) compared with controls, suggesting greater vasoconstriction. HR and BP responses were comparable. In conclusion, our results suggest early impairment of vascular function in premenopausal females with PTSD.