Sympathetic nerve activity in metabolic control--some basic concepts

A role for the sympathetic nervous system in hypertension has been looked for in relation to the 'metabolic syndrome' with associations between body weight, insulin sensitivity and hypertension. By use of microneurography human sympathetic responses to hypoglycaemia, normoglycaemic hyperinsulinaemia and food intake have been studied. A strong but differentiated influence of insulin-induced hypoglycaemia comprises increase in muscle sympathetic nerve activity (MSNA) and the sudomotor part of skin sympathetic nerve activity (SSNA), whereas vasoconstrictor SSNA is inhibited. Responses to infusion of 2-deoxy-D-glucose are identical, suggesting central nervous system glucopenia and not insulin to be the causative factor. Insulin infusion during normoglycaemia evokes a moderate increase in MSNA; SSNA and blood pressure does not change. After glucose ingestion MSNA displays a sustained increase, which is only partly elicited by insulin. A significant albeit weaker increase occurs after pure protein or fat meals, and after glucose ingestion in C-peptide-negative diabetic patients, with no insulin secretion. In healthy elderly people the MSNA response to food intake is weak, because of a high outflow already at rest; this is suggested to explain postprandial hypotension in the elderly, a paradoxical mechanism behind clinical autonomic failure. A pathophysiological role of MSNA in the metabolic syndrome with hypertension has been speculated. An association between obesity and elevated level of MSNA at rest is established; observed relationships to chronic insulin levels and hypertension are less unanimous. The adipose tissue regulating hormone leptin has become one focus of interest in ongoing attempts to elucidate a possible role of the human sympathetic nervous system in the 'metabolic syndrome' and hypertension.     

Human sympathetic nerve activity to glabrous skin does not increase during simulated diving

In humans, cardiovascular adjustment to simulated diving causes a marked increase in sympathetic outflow to intramuscular vessels and muscle vasoconstriction. Skin vasoconstriction in the hand also occurs during diving in humans. Skin nerve sympathetic activity (SSA), containing vasoconstrictor signals to glabrous skin, unexpectedly was reduced during diving in a previous study of SSA recorded in the peroneal nerve. SSA was recorded by microneurography in the median nerve in 13 healthy volunteers during simulated diving. Skin blood flow in the hand and one finger was monitored. The typical SSA response, irrespective of duration of diving and water temperature, was an increase during the control period immediately prior to immersion of the face and a sudden reduction of SSA when the face was immersed. The increase in SSA preceding the dive was accompanied by vasoconstriction, which continued during the dive, but re-dilation regularly occurred before the end of the dive. Inhibition of SSA was not total. Mental arithmetic during diving evoked strong bursts of SSA, similar to those seen normally during mental stress. It is concluded that the true response of SSA to simulated diving is an inhibition of the immediately preceding outflow, in agreement with observations of cutaneous blood flow in animals. The skin vasoconstriction recorded during simulated diving is a consequence of an SSA increase before the procedure, suggested to be a stress response before the forthcoming manoeuvre. The SSA response during simulated diving is the opposite to that of sympathetic outflow to muscle, which emphasizes the diversity of sympathetic regulation of different organ systems.     

Neurophysiological analysis of target‐related sympathetic pathways – from animal to human: similarities and differences*

The sympathetic nervous system regulates many different target tissues in the somatic and visceral domains of the body in a differentiated manner, indicating that there exist separate sympathetic pathways that are functionally defined by their target cells. Signals generated by central integration and channelled through the preganglionic neurons into the final sympathetic pathways are precisely transmitted through the para‐ and prevertebral ganglia and at the neuroeffector junctions to the effector cells. Neurophysiological recordings of activity in postganglionic neurons in skin and muscle nerves using microneurography in human subjects and in skin, muscle and visceral nerves, using conventional recording techniques in anaesthetized animals, clearly show that each type of sympathetic neuron exhibits a discharge pattern that is characteristic for its target cells and, therefore, its function. These findings justify labelling the neurons as muscle vasoconstrictor, cutaneous vasoconstrictor, sudomotor, lipomotor, cardiomotor, secretomotor neurons, etc. The discharge patterns monitor aspects of the central organization of the respective sympathetic system in the neuraxis and forebrain. They can be dissected into several distinct reflexes (initiated by peripheral and central afferent inputs) and reactions connected to central signals (related to respiration, circadian and other rhythms, command signals generated in the forebrain, etc). They are functional markers for the sympathetic final pathways. These neurophysiological recordings of the discharge patterns from functionally identified neurons of sympathetic pathways in the human and in animals are the ultimate reference for all experimental investigations that aim to unravel the central organization of the sympathetic systems. The similarities of the results obtained in the in vivo studies in the human and in animals justify concluding that the principles of the central organization of sympathetic systems are similar, if not identical, at least in the neuraxis, in both species. Future progress in the analysis of the central neuronal circuits that are associated with the different final sympathetic pathways will very much depend on whether we are able to align the human models and the animal models. Human models using microneurography have the advantage to work under awake conditions. The activity in the postganglionic neurons can be correlated with various other (afferent, centrally generated) signals, effector responses, perceptions, central changes monitored by imaging methods, etc. However, human models have considerable limitations. Animal models can be divided into in vivo models and various types of reduced in vitro models. Animal models allow using various methodological approaches (e.g., neurophysiological, pharmacological, modern anatomical tracing methods; behavioural animal models; transgenic animals), which cannot be used in the human. Interaction of the research performed in the human and animals will allow to design animal models that are relevant for diseases in which the sympathetic nervous systems is involved and to trace down the underlying pathophysiological mechanisms. The scientific questions to be asked are formulated on the basis of clinical observations resulting in testable hypotheses that are investigated in the in vivo human and animal models. Results obtained in the in vivo models lead to the formulation of hypotheses that are testable in reduced in vivo and particularly in vitro animal models. Microneurographic recordings from sympathetic postganglionic fibres in the human will keep its place in the analysis of the sympathetic nervous system in health and disease although only relatively few laboratories in the world will be able to keep the standards and expertise to use this approach. Experimental investigation of the organization of the sympathetic nervous system in animal models has changed dramatically in the last 15 years. The number of in vitro models and the methodological diversity have increased. In vivo experimentation on larger animals has almost disappeared and has been replaced by experimentation on rats, which became the species for practically all types of studies on the central organization of the sympathetic nervous system.     

Sympathetic control of spontaneous defibrillation of the heart

Department of Normal Physiology, Russian National Medical University, Moscow. (Presented by Academician of the Russian Academy of Medical Sciences V. A. Negovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 10, pp. 339–340, October, 1992.     

Sympathetic activation in human heart failure: diverse mechanisms,therapeutic opportunities

Plasma noradrenaline (NA) concentrations relate both to the severity of heart failure, and to its impact on survival, but have shortcomings that limit their usefulness as measures of sympathetic discharge. Neural recordings and the isotopic dilution method for determining organ‐specific rates of NA spillover into plasma have enhanced our understanding of mechanisms responsible for sympathetic activation. Because the arterial baroreceptor reflex control of heart rate is impaired in heart failure, a parallel reduction in the reflex inhibition of sympathetic outflow has been assumed. However, human heart failure is characterized by rapidly responsive arterial baroreflex regulation of muscle sympathetic nerve activity (MSNA), attenuated cardiopulmonary reflex modulation of MSNA, and activation of a cardiac‐specific sympatho‐excitatory reflex related to increased cardiopulmonary filling pressures. Together, these baroreceptor mediated mechanisms account only, in part, for the time course and magnitude of adrenergic activation in heart failure. Non‐baroreflex sympatho‐excitatory mechanisms include: a metaboreflex arising from exercising skeletal muscle, mediated, in part, by adenosine, co‐existing sleep apnoea, and pre‐junctional facilitation of NA release. Thus, sympathetic activation in the setting of impaired systolic function reflects the net balance and interaction between augmented excitatory and diminished inhibitory influences. Variation, between patients, in the dynamics, magnitude and progression of sympathetic activation mandates an individualized approach to investigation and therapy. Excessive sympathetic outflow to the heart and periphery can be addressed by several complimentary strategies: attenuating these sympatho‐excitatory stimuli, modulating the neural regulation of NA release, and blocking the actions of catecholamines at post‐junctional receptors.     

Sympathetic nervous control of the cerebral circulation in sleep

Cerebral vessels are extensively innervated by sympathetic nerves arising from superior cervical ganglia, and these nerves might play a protective role during the large arterial pressure surges of active sleep (AS). We studied lambs (n=10) undergoing spontaneous sleep-wake cycles before and after bilateral removal of the superior cervical ganglia (SCGx, n=5) or sham ganglionectomy (n=5). Lambs were instrumented to record cerebral blood flow (CBF, flow probe on the superior sagittal sinus), carotid arterial pressure (P(ca)), intra-cranial pressure (P(ic)), cerebral perfusion pressure (Pcp=Pca-Pic) and cerebral vascular resistance (CVR). Prior to SCGx, CBF (mL min-1) was significantly higher in AS than in Quiet Sleep (QS) and Quiet Wakefulness (QW) (17+/-2, 13+/-3, and 14+/-3 respectively, mean+/-SD, P<0.05). Following SCGx, baseline CBF increased by 34, 31, and 29% respectively (P<0.05). CVR also decreased in all states by approximately 25% (P<0.05). During phasic AS, surges of Pca were associated with transient increases in Pcp, Pic and CBF. Following SCGx, peak CBF and Pic during surges became higher and more prolonged (P<0.05). Our study is the first to reveal that tonic sympathetic nerve activity (SNA) constricts the cerebral circulation and restrains baseline CBF in sleep. SNA is further incremented during arterial pressure surges of AS, limiting rises in CBF and Pic, possibly by opposing vascular distension as well as by constricting resistance vessels. Thus, SNA may protect cerebral microvessels from excessive distension during AS, when large arterial blood pressure surges are common.     

Influence of arterial baroreceptors and intracerebroventricular guanabenz on synchronized renal nerve activity

The contributions of changes in the number of active fibres and the peak interval of synchronized neural discharges to arterial baroreflex regulated alterations in renal sympathetic nerve activity were examined in intact conscious rats. Stimulation of central nervous system α₂ adrenoreceptors with intracerebroventricular guanabenz (10, 20, 40 μg) was used to alter renal sympathetic nerve activity by a non-reflex mechanism in both intact and sinoaortic denervated (SAD) rats. Synchronized renal sympathetic nerve discharge was analysed with the sympathetic peak detection algorithm. When arterial pressure was increased from 50 mmHg to 150 mmHg in intact rats, the peak height (number of simultaneously active fibres) of synchronized discharges decreased in a sigmoidal fashion while the peak interval remained unchanged. Guanabenz produced a dose dependent inhibition of renal sympathetic nerve activity due to both a decrease in peak height and an increase in peak interval of synchronized discharges in both intact and SAD rats. Arterial baroreflex mediated changes in renal sympathetic nerve activity are due to changes in the number of simultaneously active nerve fibres. Central nervous system α₂ adrenoreceptor stimulation decreases renal sympathetic nerve activity by decreasing the number of active fibres and increasing the peak interval, acting on additional neural pathways not involved in buffering acute arterial pressure changes.     

The influence of sleep onset on the diurnal variation in cardiac activity and cardiac control

Heart rate (HR), blood pressure (BP) and autonomic nervous system (ANS) activity vary diurnally, with a reduction in HR and BP, and a shift to vagal dominance during the dark phase. However, the cause of these changes, particularly the relative influence of sleep and circadian mechanisms, remains uncertain. The present study assessed the effect of sleep onset on HR, BP, high frequency (HF) component of heart rate variability (HRV), low frequency/high frequency (LF/HF) ratio and pre-ejection period (PEP). Sleep onset was dissociated from circadian influences by having subjects go to sleep at two different circadian phases, their normal time of sleep onset (normal sleep onset, NSO), and after a delay of 3 h (delayed sleep onset, DSO). The assumption was that changes caused by sleep onset would occur in association with sleep onset, irrespective of its timing, while circadian effects would have a consistent circadian phase and be independent of when sleep onset occurred. Thirteen and 17 subjects were run in the NSO and DSO conditions, respectively. Following a 1-h adaptation period, data collection began 2 h before subjects' normal time of sleep onset and continued until morning awakening. The lights were turned out after 2 h in the NSO condition and 5 h in the DSO condition. Subjects were required to maintain a supine position throughout the experimental sessions. The night-time decrease in HR was found to be due to both sleep onset and a circadian influence, with the circadian component being more prominent. In contrast, the fall in BP was largely due to a sleep onset effect. Increased vagal activity, as reflected in the HF component and a shift to vagal dominance in the LF/HF ratio, appeared to be primarily a function of the sleep system, while sympathetic activity, as assessed by PEP, reflected a circadian influence.     

Sympathetic nerve stimulation influences mucociliary activity in the rabbit maxillary sinus

The effect of preganglionic sympathetic nerve stimulation on mucociliary activity in the rabbit maxillary sinus was investigated in vivo. Response to nerve stimulation was recorded photoelectrically and expressed as a percentage of the basal mucociliary activity prior to stimulation. Nerve stimulation (15 V, 5 ms) for 60 s at 2, 10 and 20 Hz stimulated mucociliary activity, the maximum increase being 21.1 ±1.3% at 20 Hz, an increase that pretreatment with the cholinergic antagonist atropine reduced to 14.5±2.4%, suggesting that part of the response involves cholinergic mechanisms. Nerve stimulation (10 Hz) of animals pretreated with the β-adrenoceptor antagonist propranolol reversed the mucociliary response from an increase to a decrease (-10.6± 1.6%), indicating the involvement of β-receptors in the nerve-evoked increase. Pretreatment with the α-adrenoceptor antagonist phentolamine had no effect on response to nerve stimulation. Rabbits given a combined atropine, propranolol and phentolamine blockade manifested decreased mucociliary activity in response to nerve stimulation (- 10.6± 2.1 %). Guanethidine pretreatment blocked the effect of nerve stimulation on mucociliary activity, including the observed decrease after combined blockade, indicating the effect to be mediated via sympathetic nerve fibres. The decrease in mucociliary activity in response to nerve stimulation after combined cholinergic-, β-, and α-adrenoceptor blockade suggests the presence of a nonadrenergic, non-cholinergic inhibitory mechanism. It is possible that this effect is mediated by release of neuropeptide Y, as intraarterial injections of neuropeptide Y reduce mucociliary activity in the rabbit maxillary sinus, and as neuropeptide Y is released in the upper airways upon sympathetic nerve stimulation.     

Differential Distribution of Renal Nerves in the Sympathetic Ganglia of the Rat

The renal nerve plexus comprises efferent and afferent fibers. It controls urine production and bodily fluid homeostasis. Efferent fibers to the kidney include sympathetic nerve fibers from their main ganglia, the prevertebral suprarenal ganglia (SrG), and the paravertebral sympathetic chain ganglia (ChG). In the present study, we examined topological innervation from these ganglia to the renal parenchymal segments of the left kidney of the rat. Fluoro‐Gold was injected into the rostral or caudal poles of the left kidney. Approximately 50% of the cells in the SrG of rats injected in the rostral pole were labeled, while 60% of the cells in the ChG T13 of rats injected in the caudal pole were labeled. In addition, we performed dual‐probe retrograde tracing of the nerves using two kinds of fluorescent‐conjugated cholera toxins (f‐CTbs) injected into the rostral and caudal poles of the left kidney. The cells labeled with each f‐CTb were distributed differently in the left SrG and the lower ChGs; no dual‐labeled cells were found in these ganglia. Anterograde tracing with pCAGGS‐tdTomato vector transfected into the left SrG showed that tdTomato‐labeled nerve varicosities extended to the cortical arterioles and urinary tubules. Immunohistochemistry revealed that they were positive to tyrosine hydroxylase and synaptophysin, suggesting that they possessed sympathetic nerve endings. Our results show that renal efferent nerves in the SrG may control the rostral part of the kidney and innervate the multiple effectors in the cortex. Anat Rec, 300:2263–2272, 2017. © 2017 Wiley Periodicals, Inc.     

The Sacral Autonomic Outflow Is Spinal,but Not “Sympathetic”

A recent article published in a high‐profile journal proposed to reclassify the sacral autonomic outflow as being part of the sympathetic system. In this commentary, arguments against this erroneous proposal are provided. Anat Rec, 300:1369–1370, 2017. © 2017 Wiley Periodicals, Inc.     

Sympathetic Withdrawal Augments Cerebral Blood Flow During Acute Hypercapnia in Sleeping Lambs

Study Objectives:

Cerebral sympathetic activity constricts cerebral vessels and limits increases in cerebral blood flow (CBF), particularly in conditions such as hypercapnia which powerfully dilate cerebral vessels. As hypercapnia is common in sleep, especially in sleep disordered breathing, we tested the hypothesis that sympathetic innervation to the cerebral circulation attenuates the CBF increase that accompanies increases in PaCO₂ in sleep, particularly in REM sleep when CBF is high.

Design:

Newborn lambs (n = 5) were instrumented to record CBF, arterial pressure (AP) intracranial pressure (ICP), and sleep-wake state (quiet wakefulness (QW), NREM, and REM sleep). Cerebral vascular resistance was calculated as CVR = [AP-ICP]/CBF. Lambs were subjected to 60-sec tests of hypercapnia (FiCO₂ = 0.08) during spontaneous sleep-wake states before (intact) and after sympathectomy (bilateral superior cervical ganglionectomy).

Results:

During hypercapnia in intact animals, CBF increased and CVR decreased in all sleep-wake states, with the greatest changes occurring in REM (CBF 39.3% ± 6.1%, CVR −26.9% ± 3.6%, P < 0.05). After sympathectomy, CBF increases (26.5% ± 3.6%) and CVR decreases (−21.8% ± 2.1%) during REM were less (P < 0.05). However the maximal CBF (27.8 ± 4.2 mL/min) and minimum CVR (1.8 ± 0.3 mm Hg/ min/mL) reached during hypercapnia were similar to intact values.

Conclusion:

Hypercapnia increases CBF in sleep and wakefulness, with the increase being greatest in REM. Sympathectomy increases baseline CBF, but decreases the response to hypercapnia. These findings suggest that cerebral sympathetic nerve activity is normally withdrawn during hypercapnia in REM sleep, augmenting the CBF response.

Citation:

Cassaglia PA; Griffiths RI; Walker AM. Sympathetic withdrawal augments cerebral blood flow during acute hypercapnia in sleeping lambs. SLEEP 2008;31(12):1729–1734.     

Studies on the Activity of the Sympathetic Nervous System in Essential Hypertension

Abstract

Plasma catecholamine and norepinephrine concentrations have been measured in carefully characterized ambulatory patients with essential hypertension under basal conditions and following experimental procedures known to enhance sympathetic activity. The studies have demonstrated increased levels of plasma catecholamines in patients with mild hypertension as compared with matched controls following 70° upright tilt or cold pressor testing. Considerable heterogeneity was apparent in the population of patients with essential hypertension with respect to their plasma norepinephrine concentrations. Significantly greater levels of plasma norepinephrine were present in patients with high plasma renin activity and lesser levels in patients with low renin activity than in normal renin or labile hypertensives. Blood pressure correlated significantly with plasma norepinephrine in male patients with normal renin essential hypertension but not in females. Administration of the diuretic furosemide produced an increase in plasma norepinephrine in almost all hypertensive subjects studied.

These studies suggest that peripheral sympathetic activity is abnormal in certain patients with essential hypertension. The results underscore the need to differentiate between subgroups of essential hypertension in studies relating to the role of the adrenergic system in the hypertension. The findings also suggest that the recently developed sensitive techniques for measuring plasma catecholamines or plasma norepinephrine are of value in assessing changes in peripheral sympathetic activity but that enzymatic assays of serum dopamine-beta-hydroxylase activity are probably not useful for this purpose.     

Inflammation in neurodegenerative diseases – an update

Neurodegeneration, the progressive dysfunction and loss of neurons in the central nervous system (CNS), is the major cause of cognitive and motor dysfunction. While neuronal degeneration is well‐known in Alzheimer's and Parkinson's diseases, it is also observed in neurotrophic infections, traumatic brain and spinal cord injury, stroke, neoplastic disorders, prion diseases, multiple sclerosis and amyotrophic lateral sclerosis, as well as neuropsychiatric disorders and genetic disorders. A common link between these diseases is chronic activation of innate immune responses including those mediated by microglia, the resident CNS macrophages. Such activation can trigger neurotoxic pathways leading to progressive degeneration. Yet, microglia are also crucial for controlling inflammatory processes, and repair and regeneration. The adaptive immune response is implicated in neurodegenerative diseases contributing to tissue damage, but also plays important roles in resolving inflammation and mediating neuroprotection and repair. The growing awareness that the immune system is inextricably involved in mediating damage as well as regeneration and repair in neurodegenerative disorders, has prompted novel approaches to modulate the immune system, although it remains whether these approaches can be used in humans. Additional factors in humans include ageing and exposure to environmental factors such as systemic infections that provide additional clues that may be human specific and therefore difficult to translate from animal models. Nevertheless, a better understanding of how immune responses are involved in neuronal damage and regeneration, as reviewed here, will be essential to develop effective therapies to improve quality of life, and mitigate the personal, economic and social impact of these diseases.     

Sympathetic ANS modulation of pupil diameter in emotional scene perception: Effects of hedonic content,brightness, and contrast

A series of studies investigated the effects of hedonic content, brightness, and contrast on pupil diameter during free viewing of natural scenes, assessing the amplitude of the initial light reflex and subsequent sustained pupil diameter change. Hedonic picture content varied from highly arousing scenes of erotica and violence to scenes depicting nature, babies, loss, contamination, food, and more. Despite equivalent overall picture brightness and contrast, pupil diameter still varied as a function of the local brightness of central vision at fixation. Statistical (Experiment 1) and methodological (Experiment 2, 3) solutions produced complementary data indicating that scenes of erotica and violence reliably attenuate the amplitude of the initial light reflex and prompt enhanced late diameter pupil changes, compared to other scene contents. A principal components analysis supported the hypothesis that a single sympathetically mediated process enhances pupil dilation during picture viewing, modulating both initial constriction and late diameter changes. Rather than being a subtle index of “liking,” pupil diameter is primarily sensitive to events that reliably elicit measurable sympathetic nervous system activity.     

Sleep timing is associated with diet and physical activity levels in 9–11‐year‐old children from Dunedin,New Zealand: the PEDALS study

It is well documented that short sleep duration is associated with excess body weight and poor food intake in children. It has been suggested that sleep timing behaviour may also be an important predictor of weight and other related behaviours, independent of sleep duration; however, there is a lack of research investigating these relationships. The present study investigated sleep timing in association with diet and physical activity levels in 439 children aged 9–11 years old from New Zealand. Sleep and physical activity data were collected using accelerometry, and food choice using a short food‐frequency questionnaire. Participants were classified into one of four sleep timing behaviour categories using the median split for sleep‐onset and ‐offset times. Differences between sleep timing groups for weekly consumption frequency of selected food groups, dietary pattern scores and minutes of moderate‐to‐vigorous physical activity were examined. Children in the late sleep/late wake category had a lower ‘Fruit & Vegetables’ pattern score [mean difference (95% CI): ?0.3 (?0.5, ?0.1)], a lower consumption frequency of fruit and vegetables [mean weekly difference (95% CI): ?2.9 (?4.9, ?0.9)] and a higher consumption frequency of sweetened beverages [mean weekly difference (95% CI): 1.8 (0.2, 3.3)] compared with those in the early sleep/early wake category. Additionally, children in the late sleep/late wake category accumulated fewer minutes of moderate‐to‐vigorous physical activity per day compared with those in the early sleep/early wake category [mean difference (95% CI): ?9.4 (?15.3, ?3.5)]. These findings indicate that sleep timing, even after controlling for sleep duration, was associated with both food consumption and physical activity.     

Phenylethanolamine-N-methyl Transferase (PNMT) Activity and Catecholamine Content in Chromaffin Tissue and Sympathetic Neurons in the Cod,Gadus morhua1

The activity of phenylethanolamine-N-methyl transferase (PNMT) has been measured in the chromaffin tissue of the head kidney and in the sympathetic neurons of the coeliac ganglion/splanchnic nerve in the cod. The content of adrenaline and noradrenaline in these tissues and in other adrenergically innervated tissues and blood plasma was also determined. Adrenaline dominates over noradrenaline in most sympathetically innervated tissues, in the chromaffin tissue and in blood plasma, but not in the muscularis mucosae of the swimbladder. High PNMT activity was found in the chromaffin tissue in the walls of the posterior cardinal veins, and also in sympathetic neurons. It is concluded that the adrenaline found in the sympathetic nerves may originate from intraneuronal adrenaline synthesis, but also from circulating adrenaline which is taken up and stored.     

Changes in muscle sympathetic nerve activity and calf blood flow during combined leg and forearm exercise

In order to examine efferent sympathetic nerve control of the peripheral circulation during exercise, muscle sympathetic nerve activity (MSNA), calf blood flow (CBF), heart rate (HR), blood pressure (BP) and oxygen uptake were measured during combined foot and forearm exercise. An initial period of rhythmic foot exercise (RFE) (60 min^-1 at 10% of maximal voluntary contraction (MVC) was followed by the addition of rhythmic handgrip exercise (RFE+OCCL) (60 min at 30% of MVC) and by forearm ischaemia after handgrip exercise while continuing RFE (RFE + OCCL). During RFE, CBF in the working leg, HR and oxygen increased respectively by 560%, 121% and 144% when compared with the control rest period, but MSNA (burst rate) was reduced by 13% (P > 0.05) and BP was unchanged. During RFE+RHG, HR, BP and oxygen uptake were greater than during RFE alone. There was no change in CBF, but a significant increase occurred in calf vascular resistance (CVR) and MSNA increased to 121% of the control level. During RFE + OCCL, MSNA, CVR and BP were all higher than during RFE alone, whereas HR and oxygen uptake decreased slightly, although they remained higher than the control values. The increase in CVR in the working leg and the rise in BP during RFE+RHG or RFE+OCCL might be linked to enhancement of MSNA, which may have been reflexly evoked by input from muscle metabolic receptors in the working forearm.     

The role of neuropeptide W in energy homeostasis

Neuropeptide W is the endogenous ligand for G‐protein‐coupled receptors GPR7 and GPR8. In this review, we summarize findings on the distribution of neuropeptide W and its receptors in the central nervous system and the periphery, and discuss the role of NPW in food intake and energy homeostasis.     

Sympathetic regulation of fructose secretion in the seminal vesicle of the guinea-pig

Fructose secretion of everted guinea-pig seminal vesicles was studied in vitro. Carbachol produced dose dependent increase in fructose secretion. The effect was blocked by scopolamine but not by hexamethonium, mecamylamine, tetrodotoxin or previous denervation. High concentrations of acetylcholine also increased fructose secretion. This response was not augmented by physostigmine. Methoxamine reduced secretion. Methoxamine, terbutaline, clonidine and vasoactive intestinal peptide counteracted carbachol. Field stimulation produced increased secretion that was not blocked by autonomic drugs, tetrodotoxin or previous denervation. Stimulation of the hypogastric nerve produced frequency dependent increase in fructose secretion. The effect was blocked by tetrodotoxin and scopolamine but not enhanced by physostigmine. If the hypogastric nerve was stimulated close to the seminal vesicle the response was unaffected by hexamethonium but proximal stimulation was blocked. After chronic proximal denervation of the hypogastric nerve, stimulation close to the seminal vesicle produced enhanced response. Destruction of the peripheral ganglia at the base of the seminal vesicle abolished the response. Sections showed that most secretory nervesenter the organ at its base. Phentolamine or yohimbine but not prazosine or propranolol or guanethidine enhanced the secretory response to distal hypogastric nerve stimulation. Tyramine counteracted the response but after reserpinization it was enhanced by tyramine. It is concluded that the secretory cells of the guinea-pig seminal vesicle have a sympathetic secretomotor innervation by short cholinergic neurones with a preganglionic supply via the hypogastric nerve. Inhibitory α₁ and β₂-adrenoreceptors are present on the cells but neurogenic adrenergic inhibition of the secretion is essentially prejunctional and due to activation of inhibitory α₂-receptors on the secretomotor nerves.