Biomedical subjects

S C Malpas

Publications and source records attributed to S C Malpas.

At least 19 recordsLinked to original sources

PubMed2006

Acute systemic complications in the preterm fetus after asphyxia: role of cardiovascular and blood flow responses.

1. Poor perfusion of the kidneys and gut, and associated functional impairment, are major problems in the first days of life in very preterm infants. These complications can be associated with a substantial mortality and further problems such as reduced kidney growth and chronic renal problems in later childhood. 2. There is very little information, and consequently considerable debate, about how or even whether to improve perfusion of the vital organs of this most vulnerable group of babies. Current treatments simply do not consistently improve babies' perfusion generally or kidney and gut perfusion and function in particular. 3. In this review we critically examine clinical and experimental evidence that suggests that exposure to low oxygen levels before and during birth may be a significant contributor to impaired systemic perfusion, and highlight areas requiring further research. 4. This knowledge is essential to develop and refine ways of improving perfusion of the kidneys and other vital organs in premature babies.

Acute Disease↗

PubMed2001

Sympathetic modulation of blood pressure variability.

Although sympathetic nervous activity (SNA) displays oscillations synchronous with the heart beat and respiration, and between 0.1-0.4 Hz, it is apparent that each of these frequencies does not have the same effect on the vasculature. Frequencies above 1 Hz do not produce oscillations in the vasculature but instead contribute to the mean level of vasoconstriction. Slower oscillations in SNA result in a cycle of vasoconstriction and vasodilation within the vasculature, the amplitude of which, generally decreases with increasing frequency. Some studies indicate that, within the same species, differences exist in the frequency responses between vascular beds, such as the skin and gut. This differential responsiveness is also found between the medullary and cortical vasculature regions of the rabbit kidney. Low-pass filter properties have been described in the iliac circulation of rats, and evidence has been provided that noradrenaline reuptake mechanisms are not the frequency limiting step of the vasculature response. Recent studies on isolated rat vascular smooth muscle cells suggest that sympathetic modulation of vascular tone is limited by the alpha-adrenoceptor signal transduction into the cells and not by an intrinsic inability of the cells to contract and relax at higher rates.

Animals↗

PubMed2001

Differential control of intrarenal blood flow during reflex increases in sympathetic nerve activity.

The role of renal sympathetic nerve activity (RSNA) in the physiological regulation of medullary blood flow (MBF) remains ill defined, yet regulation of MBF may be crucial to long-term arterial pressure regulation. To investigate the effects of reflex increases in RSNA on intrarenal blood flow distribution, we exposed pentobarbital sodium-anesthetized, artificially ventilated rabbits (n = 7) to progressive hypoxia while recording RSNA, cortical blood flow (CBF), and MBF using laser-Doppler flowmetry. Another group of animals with denervated kidneys (n = 6) underwent the same protocol. Progressive hypoxia (from room air to 16, 14, 12, and 10% inspired O(2)) significantly reduced arterial oxygen partial pressure (from 99 +/- 3 to 65 +/- 2, 51 +/- 2, 41 +/- 1, and 39 +/- 2 mmHg, respectively) and significantly increased RSNA (by 8 +/- 3, 44 +/- 25, 62 +/- 21, and 76 +/- 37%, respectively, compared with room air) without affecting mean arterial pressure. There were significant reductions in CBF (by 2 +/- 1, 5 +/- 2, 11 +/- 3, and 14 +/- 2%, respectively) in intact but not denervated rabbits. MBF was unaffected by hypoxia in either group. Thus moderate reflex increases in RSNA cause renal cortical vasoconstriction, but not at vascular sites regulating MBF.

Anesthesia↗

PubMed2001

Slow oscillations in blood pressure via a nonlinear feedback model.

Blood pressure is well established to contain a potential oscillation between 0.1 and 0.4 Hz, which is proposed to reflect resonant feedback in the baroreflex loop. A linear feedback model, comprising delay and lag terms for the vasculature, and a linear proportional derivative controller have been proposed to account for the 0.4-Hz oscillation in blood pressure in rats. However, although this model can produce oscillations at the required frequency, some strict relationships between the controller and vasculature parameters must be true for the oscillations to be stable. We developed a nonlinear model, containing an amplitude-limiting nonlinearity that allows for similar oscillations under a very mild set of assumptions. Models constructed from arterial pressure and sympathetic nerve activity recordings obtained from conscious rabbits under resting conditions suggest that the nonlinearity in the feedback loop is not contained within the vasculature, but rather is confined to the central nervous system. The advantage of the model is that it provides for sustained stable oscillations under a wide variety of situations even where gain at various points along the feedback loop may be altered, a situation that is not possible with a linear feedback model. Our model shows how variations in some of the nonlinearity characteristics can account for growth or decay in the oscillations and situations where the oscillations can disappear altogether. Such variations are shown to accord well with observed experimental data. Additionally, using a nonlinear feedback model, it is straightforward to show that the variation in frequency of the oscillations in blood pressure in rats (0.4 Hz), rabbits (0.3 Hz), and humans (0.1 Hz) is primarily due to scaling effects of conduction times between species.

Animals↗

PubMed2001

Long-term control of renal blood flow: what is the role of the renal nerves?

We have developed a system for long-term continuous monitoring of cardiovascular parameters in rabbits living in their home cage to assess what role renal sympathetic nerve activity (RSNA) has in regulating renal blood flow (RBF) in daily life. Blood pressure, heart rate, locomotor activity, RSNA, and RBF were recorded continuously for 4 wk. Beginning 4-5 days after surgery a circadian rhythm, dependent on feeding time, was observed. When averaged over all days RBF to the innervated and denervated kidneys was not significantly different. However, control of RBF around these mean levels was dependent on the presence of the renal sympathetic nerves. In particular we observed episodic elevations in heart rate and other parameters associated with activity. In the denervated kidney, during these episodic elevations, the increase in renal resistance was closely related to the increase in arterial pressure. In the innervated kidney the renal resistance response was significantly more variable, indicating an interaction of the sympathetic nervous system. These results indicate that whereas overall levels of RSNA do not set the mean level of RBF the renal vasculature is sensitive to episodic increases in sympathetic nerve activity.

Activity Cycles↗

PubMed2001

Dynamic relationship between sympathetic nerve activity and renal blood flow: a frequency domain approach.

Blood pressure displays an oscillation at 0.1 Hz in humans that is well established to be due to oscillations in sympathetic nerve activity (SNA). However, the mechanisms that control the strength or frequency of this oscillation are poorly understood. The aim of the present study was to define the dynamic relationship between SNA and the vasculature. The sympathetic nerves to the kidney were electrically stimulated in six pentobarbital-sodium anesthetized rabbits, and the renal blood flow response was recorded. A pseudo-random binary sequence (PRBS) was applied to the renal nerves, which contains equal spectral power at frequencies in the range of interest (<1 Hz). Transfer function analysis revealed a complex system composed of low-pass filter characteristics but also with regions of constant gain. A model was developed that accounted for this relationship composed of a 2 zero/4 pole transfer function. Although the position of the poles and zeros varied among animals, the model structure was consistent. We also found the time delay between the stimulus and the RBF responses to be consistent among animals (mean 672 +/- 22 ms). We propose that the identification of the precise relationship between SNA and renal blood flow (RBF) is a fundamental and necessary step toward understanding the interaction between SNA and other physiological mediators of RBF.

Animals↗

PubMed2000

Differential regulation of the oscillations in sympathetic nerve activity and renal blood flow following volume expansion.

Renal sympathetic nerve activity (RSNA) and renal blood flow (RBF) both show oscillations at various frequencies but the functional significance and regulation of these oscillations is not well understood. To establish whether the strength of these oscillations is under differential control we measured the frequency spectrum of RSNA and RBF following volume expansion in conscious rabbits. Seven days prior to experiment animals underwent surgery to implant an electrode for recording renal nerve activity and a flow probe for recording RBF. Volume expansion (Haemaccel, 1.5 ml min(-1) kg(-1) for 15 min) resulted in a 25 +/- 5% decrease in mean RSNA, paralleled by an increase in RBF to 60 +/- 12 ml min(-1) from resting levels of 51 +/- 11 ml min(-1). Renal denervated rabbits did not show an increase in RBF with volume expansion. Arterial baroreflexes were unaltered by volume expansion. Spectral analysis of the different frequencies in RSNA showed oscillations in RSNA between 0.2 and 0.4 Hz were selectively decreased following volume expansion (14 +/- 3 to 6 +/- 1% of total power in RSNA at < 3 Hz). A corresponding decrease in the strength of oscillations in RBF at this frequency was also seen (20 +/- 6 to 8 +/- 2%). In contrast, the strength of respiratory (0.8-2.0 Hz) and cardiac (3-6 Hz) related rhythms did not change with volume expansion. These results show that selective changes in the different frequency components of RSNA can occur. We suggest that input from cardiopulmonary receptors and/or other vascular beds, and/or altered vascular resistance after volume expansion can reduce the strength of the 0.3 Hz oscillation independent of changes in arterial baroreflex control of RSNA.

Action Potentials↗

PubMed2000

Modelling the neural control of intrarenal blood flow.

1. The aim of the present study was to produce a mathematical model that describes the way dynamic changes in renal sympathetic nerve activity affect renal, cortical and medullary blood flow. 2. Cortical blood flow (CBF) and medullary blood flow (MBF) were measured using laser-Doppler flowmetry and (total) renal blood flow (RBF) was measured by transit-time flowmetry in six pentobarbitone-anaesthetized rabbits. The renal nerves were stimulated with rectangular pulses of 2 msec width and constant voltage at frequencies of 0.5, 1, 1.5, 2 and 3 Hz. 3. An exponential function with two parameters was applied; steady state gain and a dynamic constant for the blood flow reduction with stimulation. The steady state gain coefficients were similar for RBF and CBF, but significantly less for MBF. The time taken to reach minimum flow was less for MBF than for RBF and CBF. 4. The model parameters indicate that there is differential neural control of CBF and MBF.

Algorithms↗

PubMed2000

Neural regulation of renal blood flow: a re-examination.

1. The importance of renal sympathetic nerve activity (RSNA) in the regulation of renal function is well established. However, it is less clear how the renal vasculature responds to the different mean levels and patterns of RSNA. While many studies have indicated that small to moderate changes in RSNA preferentially regulate renin secretion or sodium excretion and only large changes in RSNA regulate renal blood flow (RBF), other experimental evidence suggests that small changes in RSNA can influence RBF 2. When RSNA has been directly measured in conjunction with RBF, it appears that a range of afferent stimuli can induce reflex changes in RBF. However, many studies in a variety of species have measured RBF only during stimuli designed to reflexly increase or decrease sympathetic activity, but have not recorded RSNA. While this approach can be informative, it is not definitive because the ability of the vasculature to respond to RSNA may, in part, reflect the resting level of RSNA and, therefore, the vasoconstrictive state of the vasculature under the control conditions. 3. Further understanding of the control of RBF by RSNA has come from studies that have analysed the underlying rhythms in sympathetic nerve activity and their effect on the cardiovascular system. These studies show that the frequency-response characteristic of the renal vasculature is such that higher frequency oscillations in RSNA (above 0.6 Hz) contribute to setting the mean level of RBF. In comparison, lower frequency oscillations in RSNA can induce cyclic vasoconstriction and dilation in the renal vasculature, thus inducing oscillations in RBF. 4. In summary, the present review discusses the neural control of RBF, summarizing evidence in support of the hypothesis that RBF is under the influence of RSNA across the full range of RSNA.

Animals↗

PubMed2000

Renal SNA as the primary mediator of slow oscillations in blood pressure during hemorrhage.

Blood pressure contains a distinct low-frequency oscillation often termed the Mayer wave. This oscillation is caused by the action of the sympathetic nervous system on the vasculature and results from time delays in the baroreflex feedback loop for the control of sympathetic nerve activity (SNA) in response to changes in blood pressure. In this study, we used bilateral renal denervation to test the hypothesis that it is SNA to the kidney that contributes a large portion of the vascular resistance associated with changes in the strength of the slow oscillation in blood pressure. In conscious rabbits, SNA and blood pressure were measured during hemorrhage (blood withdrawal at 1.35 ml. min(-1). kg(-1) for 20 min). Spectral analysis identified a strong increase in power at 0.3 Hz in SNA and blood pressure in the initial compensatory phase of hemorrhage before blood pressure started to fall. However, in a separate group of renal denervated rabbits, although the power of the 0.3-Hz oscillation under control conditions in blood pressure was similar, it was not altered during hemorrhage. Wavelet analysis revealed the development of low-frequency oscillations at 0.1 Hz in both intact and denervated animals. In conclusion, we propose that changes in the strength of the oscillation at 0.3 Hz in arterial pressure during hemorrhage are primarily mediated by sympathetic activity directed to the kidney.

Animals↗

PubMed2000

Influence of pontine A5 region on renal sympathetic nerve activity in conscious rabbits.

The effects of inhibiting the neural activity in the pontine A5 region on renal sympathetic responses to baroreflex and/or chemoreflex activation were examined in conscious rabbits. Eight rabbits were chronically instrumented with guide cannulas for bilateral microinjections into the A5 area and an electrode for measuring renal sympathetic nerve activity (RSNA). Baroreflex curves were obtained under conditions of normoxia and hypoxia (10% O(2) + 3% CO(2)) after injections into the A5 region of the GABA receptor agonist muscimol or vehicle solution. Under normoxia, injections of muscimol did not affect resting RSNA or blood pressure but increased the range of the RSNA baroreflex by 24 and 33% at doses of 175 or 875 pmol, respectively, without affecting the reflex gain. Hypoxia alone increased resting RSNA by 63%, as well as the range and gain of the RSNA baroreflex by 53 and 89%, respectively, without affecting blood pressure. However, under hypoxia, muscimol increased resting RSNA by 37 and 47% but decreased the gain of the RSNA baroreflex by 19 and 34% at doses of 175 or 875 pmol, respectively, without affecting the reflex range. The effects of muscimol on RSNA were mediated via changes in the amplitude of the sympathetic bursts, whereas burst frequency remained unaffected. These data suggest that the A5 region has a little tonic influence on RSNA in conscious rabbits but serves to limit the renal sympathetic responses to baroreceptor unloading or chemoreceptor stimulation. The different changes in the baroreflex range and gain evoked by muscimol under normoxia and hypoxia indicate that the A5 modulatory action may depend on the activity of the afferent inputs to this region.

Animals↗

PubMed2000

Differential neural control of intrarenal blood flow.

To test whether renal sympathetic nerve activity (RSNA) can differentially regulate blood flow in the renal medulla (MBF) and cortex (CBF) of pentobarbital sodium-anesthetized rabbits, we electrically stimulated the renal nerves while recording total renal blood flow (RBF), CBF, and MBF. Three stimulation sequences were applied 1) varying amplitude (0.5-8 V), 2) varying frequency (0.5-8 Hz), and 3) a modulated sinusoidal pattern of varying frequency (0. 04-0.72 Hz). Increasing amplitude or frequency of stimulation progressively decreased all flow variables. RBF and CBF responded similarly, but MBF responded less. For example, 0.5-V stimulation decreased CBF by 20 +/- 9%, but MBF fell by only 4 +/- 6%. The amplitude of oscillations in all flow variables was progressively reduced as the frequency of sinusoidal stimulation was increased. An increased amplitude of oscillation was observed at 0.12 and 0.32 Hz in MBF and to a lesser extent RBF, but not CBF. MBF therefore appears to be less sensitive than CBF to the magnitude of RSNA, but it is more able to respond to these higher frequencies of neural stimulation.

Anesthesia↗

PubMed1999

Sympathetic response to stimulation of the pontine A5 region in conscious rabbits.

Studies in anaesthetized animals have shown that the pontine A5 noradrenergic region plays an important role in the sympathetic control of arterial pressure (AP). The aim of this study was to develop, in conscious rabbits, a technique for microinjections into the A5 region and examine the effects of stimulation of this region on renal sympathetic nerve activity (RSNA). In preliminary mapping experiments on four anaesthetized rabbits, electrical stimulation of the A5 region induced a pressor response ranging between 25 and 75 mmHg while unilateral injection of glutamate (100 nmol) did not change AP. The mapping experiments were used to enable guide cannulae implantation for subsequent microinjections into the A5 region. In six conscious rabbits, unilateral injection of glutamate (100 nmol) caused a consistent increase in RSNA (+45%) but did not change AP. In another eight rabbits, bilateral injection of glutamate (0.3, 3, 30 nmol) into the A5 region dose-dependently increased RSNA by 13%, 30% and 40%, respectively. In four rabbits, angiotensin II (0.3, 3, 30 pmol) injected bilaterally into the A5 region increased RSNA by 5%, 22% and 28%, respectively. In all animals the increase in RSNA was mainly mediated by increasing amplitude of sympathetic synchronized bursts while their frequency remained unchanged. However, both glutamate and angiotensin II did not change AP indicating that the sympathoexcitatory response to the A5 stimulation might be relatively confined to the renal bed. Using a novel microinjection technique developed for conscious rabbits, we found that the A5 region may provide an important excitatory and possibly selective input to the renal sympathetic preganglionic neurons.

Angiotensin II↗

PubMed1999

Effects of naloxone on the haemodynamic and renal functional responses to plasma volume expansion in conscious rabbits.

We tested whether the opioid antagonist naloxone affects responses to plasma volume expansion (PVE) in conscious rabbits. Under basal conditions, naloxone (6 mg x kg-(1) plus 0.3 mg x kg(-1) x min(-1) i.v.) had no observable effect, except to slightly reduce heart rate. During vehicle treatment, PVE (Haemaccel; 1 ml x kg(-1) min(-1) for 30 min plus 0.2 ml x kg(-1) x min(-1) for 60 min i.v.) reduced haematocrit by 7.1+/-0.8% (from 34.8+/-1.1%), and increased central venous pressure by 3.0+/-0.9 mmHg (from -2.8+/-1.5 mmHg), cardiac output by 42+/-9 ml min(-1) x kg(-1) (from 152+/-17 ml x min(-1) x kg(-1)), systemic vascular conductance by 0.49+/-0.11 ml x min(-1) x mmHg(-1) kg(-1) (from 1.58+/-0.23 ml x min(-1) x mmHg(-1) x kg(-1)), urine flow by 0.13+/-0.04 ml x kg(-)x min(-1) (from 0.12+/-0.02 ml kg(-1) x min(-1)) and sodium excretion by 21+/-5 micromol x kg(-1) min(-1) (from 5+/-2 micromol x kg(-1) x min(-1)). During naloxone treatment, the PVE-induced changes in haematocrit and central venous pressure were similar to those during vehicle treatment, but the increases in cardiac output (24+/-7 ml kg(-1) min(-1)), systemic vascular conductance (0.25+/-0.05 ml min(-1) x kg(-1) x mmHg(-1)), urine flow (0.09+/-0.03 ml x kg(-1) min(-1)) and sodium excretion (11+/-4 micromol x kg(-1) x min(-1)) were 31-49% less. These observations indicate that endogenous opioids mediate some of the circulatory and renal excretory responses to PVE in conscious rabbits.

Animals↗

PubMed1999

Resonance in the renal vasculature evoked by activation of the sympathetic nerves.

We examined the ability of different frequencies in sympathetic nerve activity (SNA) to induce oscillations in renal blood flow (RBF). In anesthetized rabbits the renal nerves were stimulated using modulated sine patterns (base frequency 5 Hz, 5-ms duration pulses) that varied in amplitude between 0 and 10 V at a frequency between 0.04 and 1.0 Hz. The strengths of the induced oscillations in RBF were calculated using spectral analysis. Although faster rhythms in simulated SNA >0.6 Hz contributed to the level of vascular tone, 95% of the power in the frequency response curve was below this frequency, indicating a low-pass filtering/integrating characteristic of the vasculature. Frequencies <0.6 Hz were associated with increasing ability to induce oscillations in RBF. The ability of an SNA rhythm at 0.6 Hz to induce a rhythm in RBF was 21 times less than that at 0.25 Hz. At 0.16 Hz there was a distinct peak in the frequency response curve, indicating the vasculature was more sensitive in this frequency band to sympathetic stimulation. Blockade of endogenous nitric oxide by NG-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg) did not alter resting RBF levels nor was the low-pass filtering/integrating characteristic of the vasculature to nerve stimulation changed (i.e., the curve was not shifted left or right); however, there was a selective increase in the sensitivity to stimulation at 0.16 Hz, i.e., larger oscillations in RBF were evoked. These results indicate an ability of SNA to induce resonant oscillations in the renal vasculature and that there may be active and passive modulators of these responses. Naturally occurring oscillations in SNA <0.6 Hz are likely to contribute to the dynamic control of RBF, ensuring it responds rapidly and with high gain to the stimuli of daily life, while filtering out the faster oscillations ensures stable glomerular filtration.

Animals↗

PubMed1998

Effect of rilmenidine on the cadiovascular responses to stress in the conscious rabbit.

Environmental stress can cause an increase in sympathetic nerve activity both in humans and animals. While centrally acting antihypertensive drugs such as rilmenidine are known to reduce sympathetic tone, it is not clear whether they also influence the cardiovascular responses to acute stress. In the present study we examined the effects of systemic treatment with rilmenidine on the sympathetic and haemodynamic responses to air jet or noise stress. Twelve conscious rabbits previously implanted with a renal nerve recording electrode were subjected to an 8 l/min stream of air directed at their face for 10 min or exposure to 10 min of white noise (approximately 85 dB). Both air jet and noise stress elicited increases in renal sympathetic nerve activity (RSNA) which were greatest in the first minute (+55+/-9% and +40+/-6%, respectively), but which quickly reached a stable level over the subsequent 9 min (+24+/-6% and +9+/-5%, respectively). This was accompanied by a small increase in heart rate (HR) and mean arterial pressure (MAP). Intravenous rilmenidine (273 microg/kg) reduced MAP from 85+/-3 mm Hg to 68+/-2 mm Hg and HR from 203+/-10 b/min to 188+/-10 b/min and lowered basal RSNA by 54%. Rilmenidine reduced the increase in RSNA seen during the first minute of air jet stress by 35% and reduced the average increase over the next 9 min by 68%. However, rilmenidine had little effect on either the initial or stable RSNA responses to noise stress. Saline treatment did not alter the RSNA responses to either air jet or noise stress. The results show that centrally-acting antihypertensive agents not only lower basal RSNA, but can differentially influence environmentally induced sympathetic responses. In addition, the differential effect of rilmenidine on noise and air jet stress suggests that they may involve quite different central processing.

Animals↗

PubMed1998

Do different levels and patterns of sympathetic activation all provoke renal vasoconstriction?

Renal sympathetic nerve activity (RSNA) is postulated to influence renal function in selective ways with changes in renal hemodynamics only occurring during high stimulus intensities. The aim of this study was to determine the renal blood flow (RBF) response to a number of stimuli designed to increase RSNA by a modest amount and assess the possibility that different afferent stimuli produce differential levels of vasoconstriction by differentially altering the pattern of RSNA. Experiments were performed in eight conscious rabbits subjected to 20 min periods of three stimuli noise stress, air jet stress or hypoxia (10% O2). RSNA was significantly increased 12 +/- 4, 31 +/- 8 and 14 +/- 5% (means of 20 min periods +/- SEM) and these effects were mirrored in the significant changes in RBF over the period of each stimuli with mean reductions of 8 +/- 1, 10 +/- 3 and 8 +/- 4% during noise, air jet stress and hypoxia respectively. Changes in plasma renin activity did not occur without changes in RBF. With regard to the pattern of RSNA discharges, hypoxia selectively increased the amplitude (number of recruited nerves) while noise and air jet stress increased both the amplitude and frequency of discharges. The role of the renal nerves in these responses and in providing a tonic level of vasoconstriction within the kidney, was demonstrated in experiments on a group of eight renal denervated animals. The renal denervated rabbits had greater resting RBF than the intact rabbits (54 +/- 1 denervated vs. 38 +/- 1 ml min(-1) intact), and RBF was not altered by any of the afferent stimuli. We conclude that small changes in RSNA, irrespective of the stimulus, modulate renal blood flow.

Acoustic Stimulation↗

PubMed1998

The rhythmicity of sympathetic nerve activity.

This review focuses on that most engaging feature of the sympathetic nervous system, its rhythmicity. In particular examining the nature of sympathetic nerve activity (SNA), its characteristics, the frequencies of these rhythms and possible mechanisms responsible for their generation. Sympathetic activity can be thought of as a complex output of the central nervous system providing subtle control over end organ function. This control is exerted in a number of frequency bands including rhythms related to the cardiac and respiratory cycles, 10 Hz, and between 0.2 and 0.4 Hz. The generation and control over the occurrence of each of these rhythms is likely to be quite separate. Although afferent feedback from sources such as baroreceptors can explain some of the rhythmical properties in each case there is good evidence for inherent generation of aspects of these rhythms. A variety of brainstem cell groups are thought to be involved in their generation with the rostral ventrolateral medulla, although unlikely to be solely responsible for tone generation, an important regulator of overall activity. SNA also varies in the number of nerves recruited to fire in each synchronized discharge. Little is known about this control other than it appears to be quite separate from the control over the timing of discharges. Spinal cord mechanisms are possibly involved. SNA frequencies above 0.7 Hz do not appear to directly induce oscillations in innervated vasculature, however, are likely to contribute to setting the level of vasconstrictive tone. Slower frequencies appear to directly cause oscillations in blood flow.

Afferent Pathways↗