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The effect of physiological changes in systemic blood pressure on the force output of working abductor pollicis (AP) muscle was studied in six normal subjects. Supramaximal tetanic stimulation at the ulnar nerve produced repeated isometric contractions at 1-s intervals. Force output declined gradually with time. During the train of contractions, subjects voluntarily contracted the knee extensors for 1 min; this raised systemic blood pressure by 29%. Force output from AP rose in parallel with blood pressure so that 18% of the contraction force lost through fatigue was recovered for each 10% increase in blood pressure. When blood pressure in the hand was kept constant despite the increased systemic pressure, force output did not rise. The results show that muscle performance is strongly affected by physiological changes in central blood pressure and suggest that sensory input concerning the adequacy of muscle performance exerts a feedback control over the increase in systemic blood pressure during muscular activity.

The actions of neuropeptide Y (NPY) at the autonomic neuroeffector junction have been attributed to two main receptor subtypes. At NPY Y1 receptors, located postsynaptically, NPY has been shown to produce vasoconstriction, or to potentiate the action of other vasoconstrictor agents. At NPY Y2 receptors, located presynaptically on nerve terminals, NPY inhibits the release of neurotransmitter from autonomic nerve terminals. In these experiments we have used the specific NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31]NPY, which lacks local constrictor activity, and have demonstrated inhibition of nerve-evoked vasoconstriction in the renal circulation of anaesthetised dogs in a way that suggests an intra-renal regional specificity. Under control conditions stimulation of the renal sympathetic nerves over a range of frequencies (1-5 Hz) reduced renal vascular conductance and glomerular filtration rate (GFR). Following the injection of the selective NPY Y2 receptor agonist, N-acetyl [Leu28,Leu31]NPY24-36, nerve-evoked reductions in renal conductance were reduced by over 45%. At the lowest stimulation frequencies, reduced vasoconstrictor activity was associated with a marked increase in GFR in the presence N-acetyl [Leu28,Leu31]NPY24-36. At both higher levels of stimulation N-acetyl [Leu28,Leu31]NPY24-36 significantly inhibited vasoconstrictor activity and attenuated the nerve-evoked reductions in GFR. Full recovery of both variables was observed 20 min after N-acetyl [Leu28,Leu31]NPY24-36 injection. N-acetyl [Leu28,Leu31]NPY24-36 produced a similar inhibition of renal vasoconstrictor activity when the renal nerves were left intact and activated reflexly. These results suggest that NPY can act via NPY Y2 receptors to inhibit sympathetic vasoconstrictor activity in the renal circulation of dogs. On the basis of the demonstrated dissociation of effects on vascular conductance and GFR, we suggest that this might result from a preferential action of the NPY Y2 agonist on sympathetic nerves supplying the afferent arteriole of the kidney.

The effects of changes in arterial perfusion across the physiological range on the fatigue of a working human hand muscle were studied in seven normal subjects. With the hand above heart level, subjects made repeated isometric contractions of the adductor pollicis muscle at 50% of maximal voluntary contraction in a 6-s on, 4-s off cycle. To assess fatigue, a maximal isometric twitch was elicited in each "off" period by electrical stimulation of the ulnar nerve. The experiment was repeated at least 2 days later with the hand at heart level. Five subjects showed faster fatigue with the arm elevated, and two subjects showed little difference in fatigue for the two conditions. Central blood pressure rose in proportion to fatigue for the subjects overall and returned quickly to its initial level afterwards. We conclude that human muscle fatigue can be increased by physiological reductions in perfusion pressure. Central blood pressure increases as the muscle fatigues, a response that may partially offset declining muscle performance.

1. To be detected, movements of the interphalangeal joint of the big toe must be greater than at other joints. This poor acuity may arise because the anatomy of the foot and ankle results in poor coupling between the toe and the muscles that operate it. To vary this coupling, the effect of ankle position on proprioceptive acuity at the toe was measured. 2. We measured proprioceptive acuity at the toe with the ankle in different positions and found that ankle plantarflexion did improve acuity. This implies that, with the ankle at mid-range or dorsiflexed, toe movement is inadequately transferred to muscle fascicles. 3. To determine actual changes in fascicle length of the toe extensor, movements of extensor hallucis longus near the toe and at the muscle-tendon junction were measured during surgical exposure in one subject. Ankle position greatly affected movement transfer from toe to muscle-tendon junction: no tendon movement was transferred with the ankle dorsiflexed, but all movement was transferred with the ankle plantarflexed. 4. When the relationship between joint rotation and muscle fascicle length measured in vivo was used to express the smallest detectable movements of the toe as proportional changes in muscle fascicle length, these detectable changes were similar to those at all other limb joints. This suggests that change in muscle fascicle length is of major interest to the nervous system.

Neuropeptide Y (NPY) is known to be co-stored and co-released from sympathetic nerve terminals. In the cardiovascular system NPY acts on two main receptor subtypes. At the postjunctional or Y1 receptor NPY causes constriction directly in addition to potentiating other vasoconstrictor agents. NPY acting at the prejunctional, or Y2 receptor, inhibits the release of neurotransmitter from autonomic nerve terminals. In these experiments we used the selective Y2 receptor agonist N-acetyl[Leu28,Leu31]NPY24-36 to examine the role of NPY in the modulation of sympathetic vascular control in skeletal muscle in anaesthetised dogs. No systemic pressor or local constrictor activity was observed in response to N-acetyl[Leu28, Leu31]NPY24-36 administration, therefore allowing us to examine the neuroinhibitory actions of NPY in the absence of direct vascular effects on blood flow. Stimulation of the sympathetic nerves to the gracilis muscle engages both sympathetic cholinergic and sympathetic adrenergic fibres and produces an initial vasodilatation followed by a slower vasoconstriction. Nerve evoked vasodilatation was inhibited by over 50% in the presence of the selective NPY Y2 agonist N-acetyl[Leu28,Leu31]NPY24-36. This dilatation was abolished by atropine, confirming its cholinergic nature. N-Acetyl[Leu28,Leu31]NPY24-36 was found to have no effect on nerve evoked vasoconstriction. The results demonstrate a NPY Y2-receptor mediated inhibition of nerve evoked sympathetic cholinergic vasodilatation but not of sympathetic vasoconstriction.

In normal human subjects, we tested whether a 20- to 30-min period of rhythmic exercise, intended to provoke strong activation of the sympathetic nerves, would lead to prolonged inhibition of vagally mediated bradycardia evoked reflexly by stimulation of the baroreceptors by neck suction. Negative pressure within the neck cuff (-40 to -80 mmHg) reflexly evoked a reproducible increase in pulse interval. Following exercise, this increase in pulse interval was reduced from 444 +/- 104 ms to 76 +/- 57 ms (mean +/- SEM). Recovery time was 42 +/- 9 min. These findings demonstrate a prolonged attenuation of cardiac vagal action following rhythmic exercise in normal human subjects. It is known that neuropeptide Y (NPY) is released from cardiovascular sympathetic nerves, that it attenuates cardiac vagal action and that plasma levels of NPY are elevated for a prolonged period after exercise. Therefore, it is proposed that NPY, released from sympathetic nerves during exercise, attenuates reflexly evoked cardiac vagal action for a prolonged period after exercise ends.

1. The effects of hydrostatic changes in perfusion pressure on performance of working fatigue-resistant muscle fibres in the hand were studied in six normal subjects. 2. Supramaximal stimuli were delivered in trains of 200 ms duration, at 1 train S-1, to the ulnar nerve proximal to the wrist to produce isometric contractions of adductor pollicis. The force of contraction was measured and, after a level contraction force was achieved, the arm was passively raised or lowered. 3. Lifting the hand 45 cm above the heart produced a decline in force output from the muscle within several seconds which, after 4 min, fell by 22% below the steady-state level. Lowering the hand 45 cm below heart level produced an 8% increase in force output. Greater changes in force output occur at higher workloads. 4. It is concluded that in human subjects, muscle performance is sensitive to changes in perfusion pressure that occur across the physiological range. At moderate work levels, force output of the working muscles in the hand can vary by up to 30% over the physiological range of blood pressure. This dependence of muscular force on blood perfusion is of potential importance to motor control during normal activities.

To examine postural stability of the head, slow, undetectable rotations of small amplitude were imposed about a vertical axis while human subjects maintained a stationary body. Six normal subjects were used. The rotations were imposed through an elastic linkage, and lasted 4 s. The amplitude of head rotation was small, approximately 0.002 rad. The imposed perturbations commenced from an unloaded resting position with the head facing forward, under four conditions (1) relaxed, eyes closed; (2) relaxed, eyes open; (3) still, eyes closed; and (4) still, eyes open. The terms "relaxed' and "still' refer to the prior instructions given to the subjects regarding how they were to hold their head. There was a near linear relationship between average torque and average head angle. The effective stiffness of the head on the neck was notably low, approximately 10 Nm rad-1. Two-way analysis of variance (ANOVA) demonstrated ability to increase mean stiffness between "relaxed' and "still' conditions by 51% (P < 0.02). Visual input did not change mean stiffness significantly. Therefore, for the rotations to have been imperceptible, either the visual shifts involved must have been imperceptible, or the eyes must have counterrotated.

In a previous study, the sensory phenomenon of "backward masking" was used to demonstrate that subjects can preprogram a single stereotyped voluntary movement or movement-sequence and that such a movement can be triggered in response to a stimulus that is not perceived (that is, a stimulus of which the subject is unaware). In the present study, visual stimuli were presented at random in one of two different locations to normal human subjects in a choice reaction-time (RT) task. When the stimulus appeared in one of the locations, subjects made a motor response. When the stimulus appeared in the other location, subjects made a different motor response. Large and small stimuli were presented in either location. In some trials, the small stimulus was followed 50 ms later by the large stimulus. The small stimulus was then "masked" by the large stimulus and could not be perceived on forced-choice testing. Despite not perceiving the test stimulus in either of its randomly selected locations, subjects were able to select and execute the motor response appropriate for each location. The RTs for responses to the masked stimulus and to the same stimulus presented without masking (and so, easily perceived) were the same. This result implies that appropriate programs for two separate movements can be simultaneously held ready for use, and that either one can be executed when triggered by specific stimuli without subjective awareness of such stimuli and so without further voluntary elaboration in response to such awareness.

The effects on vagally-induced gastric contractions of local electrical stimulation of the gastric sympathetic nerves were investigated in anaesthetised cats. Sympathetic stimulation caused an inhibition of vagally mediated gastric contractions which survived beta-adrenoceptor blockade and could not be mimicked by the alpha-adrenoceptor agonist phenylephrine. We therefore concluded that the inhibition was not predominantly dependent upon activation of alpha or beta adrenoceptors, although some effect attributable to noradrenaline could not be entirely excluded. In an attempt to determine the mechanism of this phenomenon, we administered exogenous neuropeptide Y (NPY) and galanin (GAL), both of which are known to occur as cotransmitters in some sympathetic nerves in the cat. Both NPY and GAL were able to mimic the effect of sympathetic stimulation on vagally-induced gastric contractions but their effects were variable.

1. The angular displacements necessary for 70% correct detection were determined in normal subjects at the hip, knee and ankle joints, and the interphalangeal joint of the big toe. Angular velocities between 0.1 and 50 deg s-1 were tested. The hip and knee joints were tested in slight flexion and the ankle and toe joints were tested in the mid-range of the normal excursion. The joints were carefully supported for testing and the muscles acting at the joints were relaxed. 2. When detection thresholds and velocities were assessed in terms of angular displacements and angular velocities, proprioceptive performances at the hip, knee and ankle joints were superior to that at the toe joint. 3. When detection levels and displacement velocities were expressed in terms of linear displacements and velocities at the tip of the extended toe for all four joints, instead of in angular terms, the ankle gave the best performance and the hip and knee the worst. 4. The detection level and velocity data were expressed also in terms of proportional changes in the fascicle lengths of muscles operating these joints. Analysis in these terms showed that performance was similar at the hip, knee and ankle joints, but that performance for the toe was much poorer than for the other joints. 5. These results for the hip, knee and ankle are similar to those previously measured for the elbow and distal interphlangeal joint of the finger, and are consistent with the theory that muscle fascicle length is the variable of significance to the central nervous system. However, the proprioceptive performance at the big toe is notably poorer than all other joints studied and analysed in terms of this variable.

1. This study investigated the sources of sensory information upon which normal subjects' ability to stand depends. 2. An 'equivalent body' was used to simulate the physical properties of each subject's body during standing. The modulation of ankle torque required to support the equivalent body in an upright position was similar to that required to support the subject's own body when standing. However, when balancing the equivalent body, vestibular inputs were excluded from directing the appropriate changes in ankle torque. Thus, stability of stance could be studied with (normal stance) and without (balancing equivalent body) modulation by vestibular inputs. Vision could be excluded by closing the eyes. Sensory input from the feet and ankles could be removed by local anaesthesia from prolonged ischaemia, induced by occluding blood flow with inflated pneumatic cuffs just above the ankles. With vestibular, visual and peripheral sensory inputs negated, standing could rely only upon remaining sensory inputs, notably those from sensory receptors in the leg muscles. 3. Unlike the human body, the equivalent body used to negate vestibular inputs is not segmented. Therefore, the effects on stability of having a segmented body were determined by splinting subjects during standing so that only ankle movement was possible. This was done in the presence and absence of visual stabilization. 4. For each experimental task, either standing or balancing the equivalent body, sway was recorded while posture was unperturbed. Root mean square values of sway amplitude and power spectra were used to compare conditions. 5. Every subject could balance the equivalent body in a stable way when the eyes were closed, and when the feet were anaesthetized.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Thresholds for the perception of postural sway induced by gentle perturbations were determined for five normal standing subjects. In this context we understand 'perception' to mean 'able to give a subjective report'. The thresholds for the perception of movements that were equivalent to sway in velocity and amplitude were determined when the available sensory input was limited to only one, or a pair, of the vestibular, visual, and proprioceptive systems. To examine vestibular inputs alone, vision was excluded and the whole body was moved with the ankles in a fixed position. To examine visual inputs alone, the body was kept stationary and a 'room' was moved around the subjects to simulate the relative visual-field movement that occurs during standing. To limit the available sensory input to proprioception from the legs, subjects were held stationary and balanced a load that was equivalent to their own body using their ankles. In this situation, perturbations were applied to the 'equivalent body' and these could only be perceived from the resulting ankle movements. Thresholds for perceiving ankle movements were also determined in the same posture, but with the leg muscles bearing no load. 2. The thresholds for the perception of sway during standing were very small, typically 0.003 rad at a velocity of 0.001 rad s-1, and even smaller movements were perceived as the mean velocity of the sway increased up to 0.003 rad s-1. No difference was found between the thresholds for perceiving forward sway and backward sway. Eye closure during standing did not affect the threshold for perceiving sway. 3. When sensory input was limited to proprioception from the legs, the thresholds for the perception of passive ankle movements were equivalent to the thresholds for the perception of sway during standing with all sensory inputs available. When the leg muscles were relaxed, the thresholds for perceiving ankle movements increased approximately twofold. 4. The visual thresholds for perceiving movement were higher than the proprioceptive thresholds at slower velocities of movement, but there was no difference at higher velocities. 5. Both the proprioceptive and visual thresholds were sufficiently small to allow perception of the sway that was recorded when the subjects stood normally in a relaxed manner. In contrast, the vestibular thresholds were an order of magnitude greater than the visual or proprioceptive thresholds and above the largest sway movements that were recorded during normal standing.(ABSTRACT TRUNCATED AT 400 WORDS)

Previous studies have shown that injection of galanin (GAL: 6.2 nmol/kg) causes prolonged inhibition of cardiac vagal action in anaesthetised cats. Stimulation of the cardiac sympathetic nerve (16 Hz for 5 min) also produces inhibition of cardiac vagal action, an effect which has been proposed to be due to the release of endogenous GAL from sympathetic nerves. In a previous study we tested galantide (M15) and in this study we compared galantide with two other GAL antagonists for their GAL antagonist activity in our experimental model. Each of these incorporate the N-terminal fragment GAL 1-13 and a C-terminal portion of another bioactive peptide and all are C-terminally amidated. GAL 1-13 Substance P 5-11 amide (galantide: M15: 62 nmol/kg and 156 nmol/kg), GAL 1-13 Spantide amide (C7: 156 nmol/kg) and GAL 1-13 NPY 24-36 amide (M32a: 62 nmol/kg) all significantly reduced the cardiac vagal inhibitory effect of exogenous GAL and also reduced the effect of sympathetic stimulation on subsequent cardiac vagal slowing, giving strong support to our hypothesis that GAL is involved in this phenomenon. No antagonist reduced the depressor effect of GAL. This study demonstrates the GAL antagonist properties of these agents on autonomic neuroeffector functions making them useful tools in elucidating further functions of endogenous GAL.

The effects of a long-lasting intravenous infusion of neuropeptide Y (NPY, 180 +/- 8 min, 53 +/- 4 micrograms/kg/h) on the prolonged inhibition of cardiac vagal action evoked by cardiac sympathetic nerve stimulation and bolus intravenous injections of NPY were investigated in anaesthetised dogs. Sympathetic stimulation and NPY injection were performed on four separate occasions; once in control conditions, then once early and again late in the period of NPY infusion, and then on a final occasion 60-90 min after the cessation of NPY infusion. The maximum inhibition of cardiac vagal action evoked by an injection of NPY was significantly less late in the NPY infusion when compared with the other three injection groups (ANOVA, P < 0.001). Also the time to half-recovery of this response was significantly less than that seen in the other three injection groups (ANOVA, P < 0.001). The maximum inhibition of cardiac vagal action evoked by sympathetic stimulation was significantly reduced late in the NPY infusion when compared with the other three stimulation groups (ANOVA, P < 0.0001). The time for half-recovery of this response was also less than that of the other three stimulation groups (ANOVA, P < 0.001). The results indicate that desensitisation of the vagal attenuation to both exogenous NPY and sympathetic stimulation occurred during a long-lasting period of NPY infusion. This is consistent with the proposal that NPY is a mediator of this sympathetic-evoked vagal attenuation.

1. Galantide, a putative galanin antagonist composed of twenty amino acids, caused a significant reduction in the vagal attenuating action of galanin injection (20 micrograms/kg; 6.2 nmol/kg) in anaesthetized cats at both ten times (137 micrograms/kg; 62 nmol/kg) and twenty-five times (343 micrograms/kg: 156 nmol/kg) the molar dose of galanin. Galantide did not block the depressor action of galanin in these animals. 2. Galantide, at both doses, also significantly reduced the vagal attenuating action of a 5 min period of cardiac sympathetic stimulation at 16 Hz in anaesthetized cats. 3. In anaesthetized dogs, galantide, at the same dose used in cats (137 micrograms/kg; 62 nmol/kg) had no significant effect on the vagal attenuation evoked by cardiac sympathetic stimulation or injection of neuropeptide Y (35 micrograms/kg; 8.2 nmol/kg). 4. This study therefore demonstrates antagonist properties of galantide on the vagal inhibitory action of galanin. It supports the hypothesis that the vagal inhibitory factor released by cardiac sympathetic nerve stimulation in the cat, but not the dog, is galanin, although it does not exclude the possibility of other factors playing a more minor role. Because galantide was not shown to block the depressor action of galanin, this study also suggests that there may be more than one galanin receptor subtype.

Prolonged attenuation of vagal action at the heart, proposed to be due to release of the sympathetic cotransmitter neuropeptide Y (NPY), follows stimulation of cardiac sympathetic nerves. It has been shown that pretreatment with reserpine depletes cardiac and neuronal stores of both noradrenaline and NPY, while combined pretreatment with reserpine and the ganglion blocking agent chlorisondamine reduces depletion of NPY, while still depleting noradrenaline. The effects of reserpine pretreatment and combined chlorisondamine and reserpine pretreatment on the inhibition of cardiac vagal action evoked by cardiac sympathetic nerve stimulation (16 Hz, 2 min) were compared in anaesthetised dogs. In dogs with no pretreatment (n = 6), sympathetic stimulation evoked an immediate cardio-acceleration, and a prolonged inhibition of cardiac vagal action, with a maximum percent inhibition (MPI) and time to half-recovery (T50) of 78 +/- 6% and 16 +/- 2 min respectively. In dogs pretreated with reserpine (n = 6, 1 mg/kg, 24 h), the immediate cardio-acceleration (ANOVA, P < 0.01), and the magnitude (MPI = 31.8%, ANOVA, P < 0.001) and duration (T50 = 6 +/- 1 min, ANOVA, P < 0.05) of inhibition of cardiac vagal action following sympathetic stimulation were significantly attenuated. In dogs with combined chlorisondamine (n = 5, 2 mg/kg, 48 and 24 h) and reserpine pretreatment, there was again significantly reduced cardio-acceleration (ANOVA, P < 0.01), but the inhibition of cardiac vagal action following sympathetic stimulation did not significantly differ from untreated animals (MPI = 79 +/- 8%, T50 = 21 +/- 6 min). Intravenous injections of NPY (25-50 micrograms/kg) evoked prolonged inhibition of cardiac vagal action in untreated and both groups of pretreated animals. These experiments indicate that the cardio-accelerator and vagal inhibitory capacities of sympathetic nerve stimulation can be separated, and are consistent with the sympathetic vagal inhibitory factor being NPY.

Galanin (GAL), 29 amino acid peptide, has previously been shown to inhibit cardiac vagal action, and to cause a fall in systemic blood pressure in anaesthetised cats, at a dose of 6.2 nmol/kg. Here, the biological activity of exogenous GAL fragments was assessed in anaesthetised cats. GAL 1-16 at a dose equimolar with the full GAL 1-29 peptide (6.2 nmol/kg) and at a dose five times the molar dose of GAL 1-29 (31 nmol/kg), was found to be biologically active although the effects were less than that of the full peptide. GAL 1-15 at doses up to 10-times the molar dose of GAL 1-29, however, was not active, suggesting that amino acid 16, isoleucine, is critical for activity. In addition, GAL 15-29 and 21-29 showed no biological activity at doses up to 10-times the molar dose of GAL 1-29. These results suggest that the N-terminal rather than the C-terminal end of the GAL molecule is the one responsible for most of GAL's biological activity in this preparation.

1. Stimulation of the right cardiac sympathetic nerve for 2 min at 16 Hz in the presence of either beta- or alpha- and beta-adrenoceptor blockade evoked attenuation of cardiac vagal action in eight possums: 31.3 +/- 10.3% maximum inhibition of cardiac vagal action on prolonging pulse interval, with a time to half-recovery of 4.9 +/- 1.1 min. 2. Intravenous injection of galanin (2-3.5 nmol kg-1) evoked similar inhibition of cardiac vagal action: 41.3 +/- 4.1% maximum inhibition of cardiac vagal action on pulse interval, with a time to half-recovery of 13.4 +/- 2.3 min. 3. Intravenous injection of neuropeptide Y (NPY) at greater molar doses (6.5-10 nmol kg-1) caused no inhibition of cardiac vagal action. 4. The galanin injections caused a powerful pressor response: 57.1 +/- 4.9 mmHg increase in systolic blood pressure. NPY caused a smaller pressor response, despite administration of higher molar doses: 36.7 +/- 3.0 mmHg increase in systolic blood pressure. 5. In the possum, galanin but not NPY can mimic the effects of cardiac sympathetic nerve stimulation on vagal action. Galanin also causes large pressor effects.

1. Subjects' ability to detect movements imposed at the elbow during active flexion was measured. Movements of three different angular velocities (0.04, 0.4 and 4.4 deg/s) were applied to the arm while subjects maintained one of two force levels of active flexion. The threshold magnitudes for detection of the direction of imposed movement were found. 2. All thresholds were very small. At the lowest velocity of movement the average threshold was 0.13 deg and no subject had a threshold of greater than 0.3 deg. This contrasts with thresholds of over 2 deg measured in a previous study when the muscles about the joint were relaxed. Thresholds decreased further with increasing velocity of movement. 3. No difference was found between the two levels of contraction of the elbow flexors. However, extension (stretch of the contracting muscle) and flexion thresholds were calculated separately, and smaller extensions than flexions could be detected. 4. These findings indicate that conscious detection of imposed movements is greatly enhanced during active muscle contraction. Movements which cause unloading of the contracting agonist, as well as movements which result in stretch, are more easily detected than when the muscle is contracting. The discussion focuses on possible mechanisms for this enhancement.

1. It has been demonstrated that subjects can alter the reflex stiffness of the elbow and wrist in response to imperceptibly slow perturbations applied through a complaint coupling. We used this technique to measure ankle stiffness in standing subjects as a means of examining reflex activity. 2. During unperturbed stance, a linear relationship between ankle torque and ankle angle is expressed as a load stiffness. The load stiffness predicted from a subject's measured physical dimensions corresponds closely with the value measured by standing the subject on a force platform. 3. Slow perturbations were applied at waist level, through a spring, to standing subjects. The perturbations caused sway similar in magnitude and rate to the sway of normal stance. Ankle stiffness was measured during the period when the perturbations were unperceived. The contribution to ankle stiffness of reflexes that use visual information was assessed by eye closure. The ability of reflexes based on sensory information from the legs to maintain upright posture was assessed when subjects balanced a load equivalent to their own body, in a situation where neither visual nor vestibular information could assist. Ankle stiffness was measured while the load was perturbed. 4. The results show that a simple mechanical model of stance predicts the torque-angle relationship at the ankle. This relationship determines the minimal ankle stiffness required to stand, and reflex muscle stiffness is a necessary component of this ankle stiffness. Visual, vestibular and lower limb sensorimotor reflexes each contribute to ankle stiffness; however, the local sensory reflexes alone are sufficient to stand. For responses to unperceived perturbations, standing subjects can alter their reflex ankle stiffness according to intentional set.

The effects of bolus intravenous injections of neuropeptide Y (NPY) on increases in pulse interval (PI) evoked reflexly by arterial chemoreceptor and baroreceptor stimulation were investigated in anaesthetised dogs. The arterial chemoreceptors were stimulated by rapid injections of small volumes of CO2 into the carotid sinus or brief episodes of tracheal occlusion. Intravenous injections of NPY produced a prolonged attenuation of the reflex prolongation of PI induced by both methods. Two methods of testing the arterial baroreceptor reflex were used: steady-state increases in PI evoked in response to maintained step increases in systolic arterial blood pressure (SABP) from inflation of an aortic balloon-tipped catheter, and beat-by-beat increases in PI evoked reflexly by 'ramp' increases in blood pressure caused by intravenous injections of phenylephrine. In both methods the relationship between SABP and PI is linear over the range tested (up to SABP 200 mmHg), the slope of the line indicating the sensitivity of the reflex response. Intravenous injections of NPY produced a prolonged attenuation of the baroreceptor-cardiodepressor reflex measured by both methods. No significant differences were observed between the NPY-mediated inhibition of the direct effects on PI of electrical stimulation of a vagus nerve, and its inhibition of the reflex responses of PI to chemoreceptor or baroreceptor stimulation. The results indicate that the attenuation of reflex PI responses to arterial chemoreceptor and baroreceptor stimulation following an intravenous injection of NPY can be accounted for in terms of the action of NPY on vagal nerve endings at the heart, although additional sites of action cannot be ruled out.

Prolonged attenuation of cardiac vagal action occurs following cardiac sympathetic nerve stimulation or intravenous neuropeptide Y (NPY) injections in anaesthetised dogs. Equimolar intravenous injections of galanin (GAL) had no effect on cardiac vagal action in this species. Immunohistochemical analysis of dog stellate ganglia and cardiac muscle showed that most nerve cell bodies showing tyrosine hydroxylase immunoreactivity (TH-IR) also showed immunoreactivity to both NPY and GAL. The results are consistent with the proposal that NPY released from cardiac sympathetic nerves is responsible for the prolonged inhibition of cardiac vagal action known to be caused by such stimulation. A role for GAL, shown here to exist in cardiac sympathetic nerves in the dog, has yet to be determined.

1. Stimulation of the right cardiac sympathetic nerve for 3 or 5 min at 16 Hz in the presence of effective beta-adrenoceptor blockade evoked prolonged attenuation of subsequent cardiac vagal action in anaesthetized cats. Concurrent sympathetic and vagal stimulation, both at 16 Hz for the same period of time as sympathetic stimulation alone, reduced or abolished the inhibition of vagal action which followed when sympathetic stimulation was given alone. 2. A series of three successive intravenous injections of galanin all caused attenuation of vagally induced slowing of the heart, but the effect of each injection was less than that of the previous one. A fourth injection of galanin given after a 45 or 60 min rest period showed return of sensitivity. 3. Sympathetic stimulation at 16 Hz for 5 min was less efficient in causing attenuation of vagal slowing when applied following the administration of exogenous galanin. This is consistent with galanin being the mediator of vagal attenuation following sympathetic stimulation.

Effects of neuropeptide Y (NPY 2.35-4.7 nmol) and the fragment NPY 18-36 (3.6-36 nmol) were studied in anaesthetized rats before and after vagotomy for actions on blood pressure (a postjunctional action) and on the change in pulse interval evoked by stimulation of the cut, peripheral vagus nerve (a prejunctional action). In intact rats NPY increased blood pressure. Low doses of NPY 18-36 (2.3-4.7 nmol) also increased blood pressure slightly but higher doses only transiently increased blood pressure and this was followed by a prolonged decrease in blood pressure. In vagotomised rats NPY increased blood pressure and attenuated cardiac vagal action. In higher doses the presynaptic effect of NPY 18-36 was more marked than its pressor action. NPY 18-36 (3.6-36 nmol) also increased blood pressure and attenuated cardiac vagal action. Thus, we conclude that the hypotensive action of NPY 18-36 depends on the intact vagus nerves: in the vagotomised rat NPY 18-36 has similar biological activity to NPY, but with reduced potency. To examine further the mechanism of hypotensive action of NPY 18-36 arterial rings from the central artery of the rabbit ear were also tested for direct actions of the peptides. This preparation is also suitable for testing any potentiation of contraction evoked by injection of noradrenaline. Neither NPY nor NPY 18-36 caused direct constrictor action in concentrations up to 10 microM. NPY 18-36 had no relaxing effect on constricted arterial rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Galanin (GAL) is distributed in sympathetic nerves in the cat, and exogenous GAL inhibits cardiac vagal action and lowers blood pressure in this species. This study on anaesthetised cats compares the effects on cardiac vagal action and blood pressure of human, rat and porcine GAL. Human GAL has only recently been sequenced. It is of particular interest as it is not C-terminally amidated, unlike porcine and rat GAL. Many regulatory peptides require a C-terminal amide group for their action. However, human GAL showed similar biological activity to the other (amidated) GALs here. Omission of a single amino acid (Ser6) from rat GAL significantly attenuated both cardiovascular actions studied here.

Signals generated both peripherally and centrally contribute to the group of sensations termed kinaesthesia. Many experiments report sensations of position and movement under passive relaxed conditions without muscle contraction. However, kinaesthetic acuity is probably of greater functional value when subjects are active rather than passive and, accordingly, movement detection is markedly improved by muscular contraction. One mechanism contributing to this enhancement is likely to involve muscle spindle volleys. When identical microstimulation techniques are applied to skin, joint and muscle spindle endings innervating the hand, some cutaneous afferents and some joint afferents elicit a sensation, but activation of certain other cutaneous afferents and muscle spindle afferents rarely does. Activity in more than one muscle spindle afferent may be required for kinaesthetic sensations, whereas some single cutaneous and joint afferents may have a more 'secure' central projection.

In anesthetized dogs intravenous injection of neuropeptide Y (NPY) or stimulation of the cardiac sympathetic nerve is followed by a period of attenuation of vagal action at the heart lasting from many minutes to over an hour. Peptide YY (PYY), a related peptide (but one not reported to occur in the heart or its autonomic innervation), also inhibits cardiac vagal action but is more powerful and has a longer duration action. In 5 of 9 dogs, cardiac sympathetic nerve stimulation inhibited vagal action on the heart in control conditions, but relieved preexisting inhibition when repeated in the presence of PYY. In 3 dogs, exogenous NPY inhibited cardiac vagal action in control conditions, but failed to augment preexisting inhibition in the presence of PYY. An explanation offered for these results is that when PYY is occupying receptors on vagal nerve terminals, nerve-released NPY or exogenous NPY is either unable to produce an effect, because it cannot gain access to the receptors, or displaces PYY from at least some receptors and, being less powerful than PYY in its inhibitory action, lessens the preexisting vagal attenuation. The results reported are consistent with the proposal that the factor released from the sympathetic nerves following their stimulation and which is responsible for cardiac vagal inhibition is NPY.

Vibration of the posterior muscles of the neck in human subjects induces illusions of displacement and movement of a visual target when there is no visual reference (Biguer et al., 1988). Although illusions of head movement are rarely reported by subjects, when they point to the location of the nose they demonstrate an alteration of the perceived position of the head. The kinaesthetic illusion is in a direction consistent with the visual illusion but is of smaller magnitude.

1. The effects of neuropeptide Y (NPY) and related peptide fragments on blood pressure and vagal action at the heart were compared in the anaesthetized rat. 2. A change in vagal action was taken as a measure of presynaptic activity and a change in blood pressure was taken as a measure of postsynaptic activity. 3. NPY, NPY-(13-36) and a stabilized 13-36 analogue of NPY (ANA NPY) all exerted pressor actions and attenuated vagal action at the heart. 4. On the basis of different potencies demonstrated for the pressor and vagal inhibitory actions of these peptides, the results are consistent with the proposal that there are two populations of NPY receptors.

1. Stimulation of the right cardiac sympathetic nerve for 3 min at 16 Hz in the presence of effective beta-adrenoceptor blockade evoked prolonged attention of cardiac vagal action in the cat: 40.8 +/- 5.4% maximum inhibition of cardiac vagal action on prolonging pulse interval, with half-time to recovery of 8.3 +/- 1.4 min. 2. Intravenous injection of galanin (1.6-3.1 nmol/kg) evoked prolonged attenuation of cardiac vagal action: 40.9 +/- 8.2% maximum inhibition with a half-time to recovery of 13.6 +/- 2.6 min. This effect of galanin was not significantly different from the action of sympathetic nerve stimulation. A slight depressor response (-14.4 +/- 1.9 mmHg) was seen in nine of sixteen cats. 3. Intravenous injection of neuropeptide Y (NPY) (2.8-6.3 nmol/kg) evoked slight attenuation of cardiac vagal action: 11.9 +/- 4.5% maximum inhibition of cardiac vagal action on pulse interval, with a half-time to recovery of 4.1 +/- 1.7 min. Blood pressure increased by 68.6 +/- 5.7 mmHg. 4. Following administration of guanethidine (1 mg/kg I.V.) the inhibitory effect of sympathetic nerve stimulation on cardiac vagal action was significantly reduced (P less than 0.001). The responses to exogenous NPY and galanin on vagal action were unchanged after guanethidine. 5. The prolonged attenuation of cardiac vagal action can be mimicked by exogenous galanin in the cat but not by exogenous NPY.

1. It has been demonstrated recently that, when suitably instructed, subjects could alter the stiffness at the elbow in response to a slowly and imperceptibly changing elastic load. Although evidence was provided in favour of this occurring via changes in gain of the reflex response to stretch, changes in the degree of co-contraction could not be entirely ruled out. The major objective of the present experiments was to determine if subjects could alter stiffness at the wrist in a similar task, and then to determine whether they retained this ability when co-contraction was made impossible by anaesthetizing the nerve to the wrist extensors. A second objective was to determine if changes in stiffness could be controlled independently at the wrist and elbow. 2. Subjects, with eyes closed, initially held position constant against a constant force that loaded the flexors. For the wrist, they were instructed: (i) to keep the hand as still as possible (keep position constant) or (ii) to let the hand be moved by the perturbation (keep force constant). The perturbation was an initially imperceptible elastic load whose direction (loading or unloading) could not be predicted. Subjects were also asked to indicate when the perturbation was first perceived. 3. When asked to hold position constant or force constant at the wrist, subjects demonstrated task-dependent changes in stiffness prior to perception of the perturbation. These changes in stiffness were still achieved when the nerve to the wrist extensors was anesthetized and thus co-contraction was prevented. 4. Five subjects demonstrated the ability to control stiffness independently at the wrist and the elbow although most subjects had difficulty with the task we employed to demonstrate this. 5. The results demonstrate: (i) that for the wrist, set-dependent changes in stiffness that occur prior to perception of a slowly developing perturbation can be mediated by changes in gain of reflex responses to those perturbations, and (ii) that stiffness can be controlled independently at the wrist and elbow, presumably in part by changes in gain of stretch reflexes.

1. Stimulation of cardiac sympathetic nerves caused prolonged inhibition of vagal effects on heart rate, an effect which has been proposed on the basis of previous studies to be due to neuropeptide Y or a neuropeptide Y-like substance, released from the sympathetic nerves. 2. This prolonged vagal inhibitory effect was attenuated or abolished when the sympathetic stimulation responsible was given together with continuous vagal stimulation. 3. Continuous vagal stimulation alone did not modify the ability of administered neuropeptide Y to cause inhibition of cardiac vagal action. 4. The results are consistent with the cardiac vagal nerves releasing a transmitter (probably acetylcholine) which acts on cardiac sympathetic nerve endings, inhibiting them from releasing neuropeptide Y or a neuropeptide Y-like substance.

1. Visual stimuli were presented to normal human subjects to test simple and more complex voluntary motor responses. Large and small visual stimuli were presented. In some trials, the small stimulus was followed 50 ms later by the large stimulus, so that the small stimulus was not perceived; this is the phenomenon of "backward masking." 2. Although subjects were not able to detect the masked, visual stimulus on forced-choice testing, they performed motor, reaction-time (RT) tasks in response to it. The RTs for responses to the masked stimulus were the same as those for responses to the easily perceived, nonmasked stimulus. 3. This result confirms and extends the findings of Fehrer and Biederman and was demonstrated with both simple and more complex motor responses. 4. Discussion of the findings focuses on their implications for motor control, particularly with respect to the preprogramming of voluntary movement.

The ability to detect very slow rotations, which were associated with no sense of movement, was tested at the metacarpophalangeal (MCP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints of the middle finger of human subjects. This ability was termed 'position sense'. All the joints were found to have a position sense. No difference in detections of different angular displacements was demonstrated between the joints. Contraction, after the completion of a displacement, of the muscles operating the joints did not alter the position sense. In addition, the DIP joint was also examined in a posture that functionally disengaged its flexor and extensor and no change in position sense was found.

Proprioceptive sensation in rotation of the trunk about a vertical axis was investigated in normal human subjects. Subjects pointed at the big toe with the nose to test the accuracy of positioning of the trunk. Active rotation of the head and shoulders on the stationary hips and legs to align the nose and toe, was not significantly more accurate than moving the hips, legs and toe under the fixed head and shoulders. Passive displacements were imposed on the head and shoulders, or on the hips and legs. Thresholds for the detection of these displacements were unchanged by the exclusion of vestibular stimulation. Thresholds were highest (still less than 1 degree) at the slowest angular velocity (0.1 degree/s) and became lower as the angular velocity was increased.

1. The carotid sinus nerve was electrically stimulated in dogs anaesthetized with chloralose. Stimuli (1 ms, 1-10 V, less than or equal to 1 Hz) evoked responses in single cardiac efferent fibres dissected from the cervical part of the vagus nerve. The mean latencies of these responses varied, from fibre to fibre, between 30 and 120 ms. 2. Stimuli given during the expiratory phase of the respiratory cycle evoked vagal responses with a shorter latency than similar stimuli given only during the inspiratory phase of the respiratory cycle. 3. Following the vagal response to carotid sinus nerve stimulation a period of inhibition of vagal activity, lasting 100-150 ms, occurred. Refractoriness of the responding vagal motoneurone following an action potential could not account for this post-excitatory depression. 4. The inhibitory effects of electrical stimulation of the carotid sinus nerve were further studied by applying pairs of similar electrical stimuli to the carotid sinus nerve. The second stimulus of a pair had to be given 80-100 ms after the first to evoke a second response. 5. Trains of electrical stimuli (30-100 Hz) were also studied. At low frequencies the inhibitory effect of successive stimuli on vagal responses became less marked, but at higher frequencies only the first and last stimulus of the train reliably evoked responses. For trains of stimuli at both low and high frequencies, the last stimulus of the train evoked a vagal response, which was succeeded by a period of inhibition of vagal firing: this inhibition was then followed by further excitation before vagal discharge returned to resting levels.

Normal adult subjects attempted, with vision excluded, to match the position of the left index finger by pointing to it with the right one, using only flexion-extension movements at the right elbow. An elastic load applied at the right wrist was altered from trial to trial. When instructed to align the fingers, subjects were found to select the position of the right forearm by taking into account both a position signal and some measure of the force exerted by the elbow flexors. When instructed to match a target force, instead of position, the subjects were able to give greater weighting to signals of force than in the position matching task.

We have studied the appreciation of heaviness in two groups of subjects; in 8 patients with varying degrees of unilateral 'upper motor neuron' weakness but without sensory symptoms or signs, and in 10 volunteers during partial curarization of the forearm and hand. In all experiments the subjects matched a reference weight lifted on the weak side with a variable weight on the strong side to provide an objective indication of the heaviness of the reference weight. Patients matched the weights of tennis balls filled with mercury or weights lifted by extending the index finger. Weights were judged as heavier when lifted by the weakened side both in the hemiparetic patients and in normal subjects weakened with curare. In both the hemiparetic patients and the subjects weakened with curare peripheral sensory information would signal the forces exerted in lifting the weight; however, both groups of subjects clearly placed more reliance on the effort that was being put into the contraction than on peripheral tensions achieved. The concept that we rely in part on a sensing command to the motoneurons when estimating weight agrees with observations by Holmes on patients with unilateral cerebellar dysfunction, and with recent physiological experiments.