Elevated large-artery stiffness is recognized as an independent predictor of cardiovascular and all-cause mortality. The mechanisms responsible for such stiffening are incompletely understood. ...Several recent cross-sectional and acute experimental studies have examined whether sympathetic outflow, quantified by microneurographic measures of muscle sympathetic nerve activity (MSNA), can modulate large-artery stiffness in humans. A major methodological challenge of this research has been the capacity to evaluate the independent neural contribution without influencing the dynamic blood pressure dependence of arterial stiffness. The focus of this review is to summarize the evidence examining
) the relationship between resting MSNA and large-artery stiffness, as determined by carotid-femoral pulse wave velocity or pulse wave reflection characteristics (i.e., augmentation index) in men and women;
) the effects of acute sympathoexcitatory or sympathoinhibitory maneuvers on carotid-femoral pulse wave velocity and augmentation index; and
) the influence of sustained increases or decreases in sympathetic neurotransmitter release or circulating catecholamines on large-artery stiffness. The present results highlight the growing evidence that the sympathetic nervous system is capable of modulating arterial stiffness independent of prevailing hemodynamics and vasomotor tone.
Circadian rhythms are ubiquitous in eukaryotes, and coordinate numerous aspects of behaviour, physiology and metabolism, from sleep/wake cycles in mammals to growth and photosynthesis in plants. This ...daily timekeeping is thought to be driven by transcriptional-translational feedback loops, whereby rhythmic expression of 'clock' gene products regulates the expression of associated genes in approximately 24-hour cycles. The specific transcriptional components differ between phylogenetic kingdoms. The unicellular pico-eukaryotic alga Ostreococcus tauri possesses a naturally minimized clock, which includes many features that are shared with plants, such as a central negative feedback loop that involves the morning-expressed CCA1 and evening-expressed TOC1 genes. Given that recent observations in animals and plants have revealed prominent post-translational contributions to timekeeping, a reappraisal of the transcriptional contribution to oscillator function is overdue. Here we show that non-transcriptional mechanisms are sufficient to sustain circadian timekeeping in the eukaryotic lineage, although they normally function in conjunction with transcriptional components. We identify oxidation of peroxiredoxin proteins as a transcription-independent rhythmic biomarker, which is also rhythmic in mammals. Moreover we show that pharmacological modulators of the mammalian clock mechanism have the same effects on rhythms in Ostreococcus. Post-translational mechanisms, and at least one rhythmic marker, seem to be better conserved than transcriptional clock regulators. It is plausible that the oldest oscillator components are non-transcriptional in nature, as in cyanobacteria, and are conserved across kingdoms.
Body condition can have important fitness consequences, but measuring body condition of live animals from wild populations has been the subject of much recent debate. Using the residuals from a ...regression of body mass on a linear measure of body size is one of the most common methods of measuring condition and has been used in many vertebrate taxa. Recently, the use of this method has been criticized because assumptions are likely violated. We tested several assumptions regarding the use of this method with body composition and morphometric data from five species of small mammals and with statistical simulations. We tested the assumptions that the relationship between body mass and body size is linear, and that the proportion of mass associated with energy reserves is independent of body size. In addition, we tested whether the residuals from reduced major axis (RMA) regression or major axis (MA) regression performed better than the residuals from ordinary least squares (OLS) regression as indices of body condition. We found no evidence of nonlinear relationships between body mass and body size. Relative energy reserves (fat and lean dry mass) were generally independent or weakly dependent on body size. Residuals from MA and RMA regression consistently explained less variation in body composition than OLS regression. Using statistical simulations, we compared the effects of violations of the assumption that true condition and residual indices are independent of body size on the OLS, MA, and RMA procedures and found that OLS performed better than the RMA and MA procedures. Despite recent criticisms of residuals from mass-size OLS regressions, these indices of body condition appear to satisfy critical assumptions. Although some caution is warranted when using residuals, especially when both inter-individual variation in body size and measurement error are high, we found no reason to reject OLS residuals as legitimate indices of body condition.
Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) reduce plasma cholesterol and improve endothelium-dependent vasodilation, inflammation and oxidative stress. A 'pleiotropic' property of ...statins receiving less attention is their effect on the autonomic nervous system. Increased central sympathetic outflow and diminished cardiac vagal tone are disturbances characteristic of a range of cardiovascular conditions for which statins are now prescribed routinely to reduce cardiovascular events: following myocardial infarction, and in hypertension, chronic kidney disease, heart failure and diabetes. The purpose of the present review is to synthesize contemporary evidence that statins can improve autonomic circulatory regulation. In experimental preparations, high-dose lipophilic statins have been shown to reduce adrenergic outflow by attenuating oxidative stress in central brain regions involved in sympathetic and parasympathetic discharge induction and modulation. In patients with hypertension, chronic kidney disease and heart failure, lipophilic statins, such as simvastatin or atorvastatin, have been shown to reduce MNSA (muscle sympathetic nerve activity) by 12-30%. Reports concerning the effect of statin therapy on HRV (heart rate variability) are less consistent. Because of their implications for BP (blood pressure) control, insulin sensitivity, arrhythmogenesis and sudden cardiac death, these autonomic nervous system actions should be considered additional mechanisms by which statins lower cardiovascular risk.
Key points
Central chemoreceptor stimulation, by hypercapnia (acidosis), and peripheral, by hypoxia plus hypercapnia, evoke reflex increases in ventilation and sympathetic outflow.
The assumption ...that central or peripheral chemoreceptor‐mediated sympathetic activation elicited when PCO2 increases parallels concurrent ventilatory responses is unproven.
Applying a modified rebreathing protocol that equilibrates central and peripheral chemoreceptor PCO2 whilst clamping O2 tension at either hypoxic or hyperoxic concentrations, the independent ventilatory and muscle sympathetic stimulus–response properties of the central and peripheral chemoreflexes were quantified and compared in young men.
The novel findings were that ventilatory and sympathetic responses to central and peripheral chemoreflex stimulation are initiated at similar PCO2 recruitment thresholds but individual specific sympathetic responsiveness cannot be predicted from the ventilatory sensitivities of either chemoreceptor reflex.
Such findings in young men, if replicated in heart failure or hypertension, should temper present enthusiasm for trials targeting the peripheral chemoreflex based solely on ventilatory responsiveness to non‐specific chemoreceptor stimulation.
In humans, stimulation of peripheral or central chemoreceptor reflexes is assumed to evoke equivalent ventilatory and sympathetic responses. We evaluated whether central or peripheral chemoreceptor‐mediated sympathetic activation elicited by increases in CO2 tension (PCO2) parallels concurrent ventilatory responses. Twelve healthy young men performed a modified rebreathing protocol designed to equilibrate central and peripheral chemoreceptor PCO2 tensions with end‐tidal PCO2 (P ETC O2) at two isoxic end‐tidal PO2 (P ET O2) such that central responses can be segregated, by hyperoxia, from the net response (hypoxia minus hyperoxia). Ventilation and muscle sympathetic nerve activity (MSNA) were recorded continuously during rebreathing at isoxic P ET O2 of 150 and 50 mmHg. During rebreathing, the P ETC O2 values at which ventilation (L min−1) and total MSNA (units) began to rise were identified (P ETC O2 recruitment thresholds) and their slopes above the recruitment threshold were determined (sensitivity). The central chemoreflex recruitment threshold for ventilation (46 ± 3 mmHg) and MSNA (45 ± 4 mmHg) did not differ (P = 0.55) and slopes were 2.3 ± 0.9 L min−1 mmHg−1 and 2.1 ± 1.5 units mmHg−1, respectively. The peripheral chemoreflex recruitment thresholds, at 41 ± 3 mmHg for both ventilation and MSNA were lower (P < 0.05) compared to the central chemoreflex recruitment thresholds. Peripheral chemoreflex sensitivity was 1.7 ± 0.1 L min−1 mmHg−1 for ventilation and 2.9 ± 2.6 units mmHg−1 for MSNA. There was no relationship between the ventilatory and MSNA sensitivity for either the central (r2 = 0.01, P = 0.76) or peripheral (r2 = 0.01, P = 0.73) chemoreflex. In healthy young men, ventilatory and sympathetic responses to central and peripheral chemoreceptor reflex stimulation are initiated at similar P ETC O2 recruitment thresholds but individual ventilatory responsiveness does not predict sympathetic sensitivities of either chemoreflex.
Key points
Central chemoreceptor stimulation, by hypercapnia (acidosis), and peripheral, by hypoxia plus hypercapnia, evoke reflex increases in ventilation and sympathetic outflow.
The assumption that central or peripheral chemoreceptor‐mediated sympathetic activation elicited when PCO2 increases parallels concurrent ventilatory responses is unproven.
Applying a modified rebreathing protocol that equilibrates central and peripheral chemoreceptor PCO2 whilst clamping O2 tension at either hypoxic or hyperoxic concentrations, the independent ventilatory and muscle sympathetic stimulus–response properties of the central and peripheral chemoreflexes were quantified and compared in young men.
The novel findings were that ventilatory and sympathetic responses to central and peripheral chemoreflex stimulation are initiated at similar PCO2 recruitment thresholds but individual specific sympathetic responsiveness cannot be predicted from the ventilatory sensitivities of either chemoreceptor reflex.
Such findings in young men, if replicated in heart failure or hypertension, should temper present enthusiasm for trials targeting the peripheral chemoreflex based solely on ventilatory responsiveness to non‐specific chemoreceptor stimulation.
Nitrogen acquisition is a major challenge for herbivorous animals, and the repeated origins of herbivory across the ants have raised expectations that nutritional symbionts have shaped their ...diversification. Direct evidence for N provisioning by internally housed symbionts is rare in animals; among the ants, it has been documented for just one lineage. In this study we dissect functional contributions by bacteria from a conserved, multi-partite gut symbiosis in herbivorous Cephalotes ants through in vivo experiments, metagenomics, and in vitro assays. Gut bacteria recycle urea, and likely uric acid, using recycled N to synthesize essential amino acids that are acquired by hosts in substantial quantities. Specialized core symbionts of 17 studied Cephalotes species encode the pathways directing these activities, and several recycle N in vitro. These findings point to a highly efficient N economy, and a nutritional mutualism preserved for millions of years through the derived behaviors and gut anatomy of Cephalotes ants.
Muscle sympathetic activation in heart failure with reduced ejection fraction (HFrEF) has been attributed, on the basis of multiunit recordings, to attenuated inhibitory feedback from ...stretch-sensitive cardiopulmonary mechanoreceptors. However, such preparations integrate 2 populations of single units exhibiting directionally opposite firing when atrial pressure is perturbed. We tested the hypothesis that the proportion of single units firing paradoxically when filling pressure increases is augmented in HFrEF.
Muscle sympathetic nerve activity and estimated central venous pressure were recorded during nonhypotensive lower body negative pressure (LBNP; -10 mm Hg) and nonhypertensive positive pressure (LBPP; +10 mm Hg) in 11 treated HFrEF (left ventricular ejection fraction 25 ± 6% mean ± standard deviation) patients and 14 similarly aged controls. Single-unit muscle sympathetic nerve activity discharge was termed either anticipated, if firing frequency exhibited classic negative-feedback responses, or paradoxical. LBNP and LBPP had no heart rate, stroke volume, or blood pressure effects (P>0.05). Estimated central venous pressure decreased with LBNP (P<0.05), increased with LBPP (P<0.05), and was consistently higher in HFrEF (P<0.05). During LBNP, the ratio of single units with anticipated and paradoxical discharge was similar in HFrEF (18:7) and controls (27:5), whereas LBPP elicited paradoxical reflex excitation in a greater proportion of HFrEF single units (7:18 versus 24:6; P=0.0001). Consequently, LBPP increased mean single-unit firing frequency (P<0.05) and did not inhibit multiunit muscle sympathetic nerve activity of HFrEF subjects (P<0.05 versus controls). Firing of 12/18 HFrEF (but no control) single units increased during both LBPP and LBNP.
These findings provide the first evidence in human HFrEF for an augmented excitatory cardiopulmonary-muscle sympathetic nerve activity reflex response to increased preload, incorporating 2 distinct single-unit populations with differing firing properties.
Corporations have a great effect on the health of Canadians.
Good companies create jobs, sell valued products at market value, pay a living wage, empower employees, have progressive human resource ...policies (parental, mental health leaves, workplace wellness programs, day care), and pay their appropriate corporate taxes. They embrace corporate social responsibility and some have a triple bottom line – people, planet and profits. More good corporations are needed.
But others are selling products that are damaging to health and the environment, at prices that do not account for these damaging effects and often target consumers that are ill-informed and susceptible (e.g., children). These include businesses involving tobacco, alcohol, drugs, junk foods and beverages, resource extraction, arms production and the electronic media.
Governments have a responsibility to take action when the market mechanism fails in this way.
A priority for action is the food and beverage sector. The overconsumption of sugar, fat and salt is causing a rising prevalence of all the major chronic diseases, rising health care costs and declining population health and productivity. Urgent government action is required: taxation, advertising and sales restrictions, and a salt reduction program.
Obstructive apnea during sleep elevates the set point for efferent sympathetic outflow during wakefulness. Such resetting is attributed to hypoxia-induced upregulation of peripheral chemoreceptor and ...brain stem sympathetic function. Whether recurrent arousal from sleep also influences daytime muscle sympathetic nerve activity is unknown. We therefore tested, in a cohort of 48 primarily nonsleepy, middle-aged, male (30) and female (18) volunteers (age: 59±1 years, mean±SE), the hypothesis that the frequency of arousals from sleep (arousal index) would relate to daytime muscle sympathetic burst incidence, independently of the frequency of apnea or its severity. Polysomnography identified 24 as having either no or mild obstructive sleep apnea (apnea-hypopnea index <15 events/h) and 24 with moderate-to-severe obstructive sleep apnea (apnea-hypopnea index >15 events/h). Burst incidence correlated significantly with arousal index (r=0.53; P<0.001), minimum oxygen saturation (r=-0.43; P=0.002), apnea-hypopnea index (r=0.41; P=0.004), age (r=0.36; P=0.013), and body mass index (r=0.33; P=0.022) but not with oxygen desaturation index (r=0.28; P=0.056). Arousal index was the single strongest predictor of muscle sympathetic nerve activity burst incidence, present in all best subsets regression models. The model with the highest adjusted R
(0.456) incorporated arousal index, minimum oxygen saturation, age, body mass index, and oxygen desaturation index but not apnea-hypopnea index. An apnea- and hypoxia-independent effect of sleep fragmentation on sympathetic discharge during wakefulness could contribute to intersubject variability, age-related increases in muscle sympathetic nerve activity, associations between sleep deprivation and insulin resistance or insomnia and future cardiovascular events, and residual adrenergic risk with persistence of hypertension should therapy eliminate obstructive apneas but not arousals.
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