Differentiation of sympathetic activity at the spinal level in Response to central cold stimulation

Summary Thermally induced adjustments of skin blood flow in chronically spinalized dogs may occur without alterations of arterial pressure and heart rate. In lightly anesthetized rabbits with chronic spinal transection at the level of C₆/C₇, the question was investigated, whether the isolated spinal cord can produce differentiated changes of regional sympathetic activity as a response to central cold stimulation.Selective cooling of the thoraco-lumbar spinal cord in chronically spinalized rabbits induced an increase in vasoconstrictor tone of the ear skin vessels as indicated by a drop of ear skin temperature at constant core and ambient air temperatures. Simultaneously, a decrease of activity in a splanchnic nerve branch was observed. Arterial pressure and heart rate remained unaffected on the average. 24 h after spinal transection, this response seemed to be less pronounced than 3 or more days after the operation. The presented results show that the pattern of regional vasomotor responses induced by central cold stimulation is, on principle, identical in intact and chronically spinalized rabbits. Therefore, the vasomotor pattern described in spinalized animals seems to represent a thermoregulatory response mediated by a vicarious spinal control system.     

Regional differentiation of sympathetic activity during hypothalamic heating and cooling in anesthetized rabbits

Summary In anesthetized rabbits immobilized with succinyl choline, the discharges of sympathetic efferents supplying cutaneous and visceral regions were simultaneously recorded. The effects of thermal stimulation of the hypothalamic region were tested on the basis of the integrated discharges. During hypothalamic heating cutaneous sympathetic activity decreased, corresponding to increased ear blood flow, while visceral sympathetic activity increased. During hypothalamic cooling there was, on the average, no significant change of regional sympathetic activity. However, in single experimental periods an increase of cutaneous and a decrease of visceral sympathetic activity was found.The observed responses of regional sympathetic activity were compared with findings about regional cutaneous and intestinal blood flow under the same thermal stimulus and further with corresponding former investigations on regional blood flow and regional sympathetic activity during spinal thermal stimulation. It is suggested by this comparison that regional differentiation of sympathetic activity represents a specific thermoregulatory response of the vasomotor system mediated by the hypothalamic thermoregulatory center.     

Regional differentiation of sympathetic activity during peripheral heating and cooling in anesthetized rabbits

Summary Thermal stimuli applied to roughly one half of the body skin in anesthetized and paralyzed rabbits evoked antagonistic changes of regional sympathetic activity. Peripheral cooling resulted in an increase of cutaneous sympathetic activity, while visceral sympathetic activity decreased. Peripheral heating induced a decrease of cutaneous sympathetic activity and simultaneously an increase of visceral sympathetic activity. The same antagonism has been found during central nervous thermal stimulation at different levels. This identity of vasomotor patterns reveals that qualitative differentiation of regional outflow represents a typical thermoregulatory response of the sympathetic system.     

Antagonistic changes of blood flow and sympathetic activity in different vascular beds following central thermal stimulation

Summary Blood flow in arteries mainly supplying cutaneous, muscular or intestinal vascular regions and aortic blood flow were measured with an electromagnetic flowmeter in anesthetized dogs immobilized with succinyl choline. Up to 3 flows were recorded simultaneously with mean arterial pressure during thermal stimulation of the spinal cord at constant, neutral ambient air temperatures.In conformity with earlier observations, skin blood flow increased during moderate and strong spinal cord heating and was reduced during spinal cord cooling. Conversely, intestinal blood flow decreased during heating in all experiments and increased during cooling in 5 out of 10 experimental animals.Aortic blood flow and muscle blood flow did not change substantially during either heating or cooling. Arterial pressure showed a moderate rise during strong heating, but was not influenced by cooling and moderate heating.The changes of blood flow distribution observed in the experiments are in keeping with results obtained under external thermal stimulation. It is assumed that the antagonistic changes of blood flow in the cutaneous and intestinal vascular beds were induced by antagonistic changes of sympathetic vasoconstrictor activity.A portion of this work was presented at the 37. Congress of the Deutsche Physiologische Gesellschaft, 10.–11. April 1970 [Pflügers Arch.316, R 25, (1970)].     

Hypoxia and hypercapnia in asphyctic differentiation of regional sympathetic activity in the anesthetized rabbit

Summary The contributions of hypoxia and of hypercapnia to the differentiated changes of regional sympathetic activity during asphyxia were investigated in anesthetized, paralyzed rabbits. Under artificial ventilation with gas mixtures of various O₂ and CO₂ contents, the discharges of a postganglionic nerve twig accompanying the retroauricular artery (cutaneous sympathetic) and of a splanchnic nerve branch (visceral sympathetic) were recorded. PaO₂, PaCO₂, pH, arterial pressure, and heart rate were measured.Moderate hypoxia (PaO₂ 27.2 Torr) induced a differentiated response of regional sympathetic activity similar to that observed during moderate asphyxia, i.e. increase of visceral and decrease of cutaneous sympathetic activity. During severe hypoxia (PaO₂ 16.4 Torr) both visceral and cutaneous sympathetic activity increased, the latter after a temporary decrease.—During hypercapnia (PaCO₂ 59.3 Torr) only a slight increase of visceral sympathetic activity was observed, while cutaneous sympathetic activity did not change.—It is concluded that the differentiated responses of the sympathetic nervous system during asphyxia are caused mainly by hypoxia.     

交感神经在肺泡缺氧性肺血管收缩反应中的作用

在大鼠毁髓模型上观察缺氧与不缺氧情况下电刺激肺血管的脊髓交感中枢时体、肺循环的变化。常氧时电刺激脊髓T_(1～3)节段时P_(pa)、PVR增高(P<0.05);毁髓去神经支配大鼠吸入12%O_2低氧气体后仍能引起肺血管收缩反应(HPV),但PVR上升幅度较正常大鼠降低。在缺氧基础上电刺激T_(1～3)节段引起P_(pa)、PVR大幅度增高(P<0.05),约为常氧时电刺激效应的二倍;酚妥拉明可抑制这一反应。提示交感神经兴奋对HPV的形成有一定的促进作用。缺氧时体循环对交感兴奋的反应减弱。     

Regional differentiation of sympathetic nerve activity during fever caused by intracerebroventricular injection of PGE2

In urethane-anesthetized rabbits prostaglandin E₂ (PGE₂) injected into a lateral cerebral ventricle (icv) produced hyperthermia. During the phase of rising rectal temperature, renal sympathetic activity monitored by multi-unit recording was reduced while the drop of ear skin temperature indicated cutaneous sympathetic activation. These reciprocal changes in activity corresponded to those typical for cold stress as well as for the phase of rising body temperature in fever induced by endotoxic lipopolysaccharides (LPS). However, a slight early stimulation of the heart rate after icv PGE₂, contrasted to the initial reductions seen with LPS fever and in the cold. After sino-aortic denervation renal sympathetic inhibition in response to icv PGE₂ was reduced but not abolished. After cervical vagotomy the antagonism between cutaneous and visceral sympathetic activity and the increase in heart rate became more prominent. During the phase of subsiding hyperthermia after icv PGE₂, renal sympathetic activity returned to its control level, but, unlike LPS fever, did not exceed it. The results of this study indicate that the reciprocal changes in cutaneous and renal sympathetic activity, but not of sympathetic outflow to the heart, are identical during the phase of rising temperature in PGE₂ and LPS fever. During the phase of subsiding hyperthermia, renal sympathetic activities change to different extents in PGE₂ and LPS fever.     

Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin

Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure(CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity.We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II(Ang II) in the paraventricular nucleus(PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex.Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks(15 mg/kg).Six weeks after the first injection,the rats underwent anesthesia with urethane and α-chloralose.After vagotomy and baroreceptor denervation,cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure(MAP) response to epicardial application of capsaicin(1.0 nmol).The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity.The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats.Bilateral PVN microinjection of angiotensin II(Ang II) caused larger responses of the cardiac sympathetic afferent reflex,baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats.These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure.     

Antidiuretic responses to thermal stimulation of hypothalamus and spinal cord in the conscious goat

Summary At various ambient temperatures the effects of hypothalamus temperature and spinal cord temperature on urine formation and heat production were studied in conscious goats with chronically implanted thermodes. At neutral air temperature cooling hypothalamus or spinal cord induced a fall in urine volume and a rise in urine osmolality. This antidiuretic response was concurrent with a rise in heat production. Simultaneous occurrence of antidiuresis and increased heat production was also found after cessation of hypothalamic warming. At hot ambient temperature cooling hypothalamus affected neither urine formation nor heat production. Since hypothalamic cooling and spinal cord cooling produce identical effects on kidney function it is concluded that this response is linked to the complex cold defence activity as a whole. The predominent change of free water clearance is tentatively interpreted as caused by an increased ADH concentration in the blood during the cold defence activity.     

高交感活性诱导的大鼠心肌损伤模型中氧化应激的受体调控机制*

 目的：研究高交感活性诱发大鼠心肌损伤的氧化应激受体调控机制。方法：Sprague-Dawley (SD)大鼠随机分为对照组、模型组、普萘洛尔（Pro) 组、哌唑嗪(Praz)组、普萘洛尔+哌唑嗪 (Pro+Praz) 组、维生素E(VE)组及普萘洛尔+哌唑嗪+维生素E (Pro+Praz+VE) 组,除对照组外其余各组均腹腔注射去甲肾上腺素(NE) 复制高交感活性引起的心肌损伤模型,同时灌胃给予相应药物,连续给药16 d,期间监测各组动物体重的变化。16 d后进行心室重构指标（心指数和羟脯氨酸含量）、病理组织学检查、氧化/抗氧化指标（MDA、SOD、CAT、GSH-Px和T-AOC）和能量代谢指标（Na+-K+ATPase和Ca2+-Mg2+ATPase）分析。结果：从第9天开始,模型组动物体重与对照组的比较差异有统计学意义（P<0.05）,心指数和左心室肥厚明显增加,氧化/抗氧化和能量代谢障碍;Pro、Praz、Pro+Praz和VE各组均出现不同程度的动物体重、心指数、左心室肥厚和氧化/抗氧化失衡的改善;Pro、Praz和Pro+Praz能明显升高左心室Na+-K+ATPase和Ca2+-Mg2+ATPase的活性,Pro+Praz作用最明显（P<0.05）。结论：肾上腺素受体依赖是高交感活性诱导心肌氧化应激损伤的重要途径。     

Evaluation of sympathetic vasoconstrictor response following nociceptive stimulation of latent myofascial trigger points in humans

Aim: Myofascial trigger points (MTrPs) are a major cause of musculoskeletal pain. It has been reported that stimulation of a latent MTrP increases motor activity and facilitates muscle pain via activation of the sympathetic nervous system. However, the magnitude of the sympathetic vasoconstrictor response following stimulation of MTrP has not been studied in healthy volunteers. The aims of this study were to (1) evaluate the magnitude of the vasoconstrictor response following a nociceptive stimulation (intramuscular glutamate) of MTrPs and a breath‐hold manoeuvre (activation of sympathetic outflow) and (2) assess whether the vasoconstrictor response can be further modulated by combining a nociceptive stimulation of MTrPs and breath‐hold. Methods: Fourteen healthy subjects were recruited in this study. This study consisted of four sessions (normal breath group as control, breath‐hold group, glutamate MTrP injection group and glutamate MTrP injection + breath‐hold group). Skin blood flow and skin temperature in both forearms were measured with laser Doppler flowmetry and infrared thermography, respectively, in each session (before the treatment, during the treatment and after the treatment). Results: Glutamate injection into MTrPs decreased skin temperature and blood flow in the peripheral area. The magnitudes of the reduction were comparable to those induced by the breath‐hold manoeuvre, which has been used to induce sympathetic vasoconstrictor response. Conclusion: The combination of glutamate injection into latent MTrPs together with the breath‐hold manoeuvre did not result in further decrease in skin temperature and blood flow, indicating that sympathetic vasoconstrictor activity is fully activated by nociceptive stimulation of MTrPs.     

Involvement of central H1 and H2 receptors in water intake induced by hyperosmolarity, hypovolemia and central cholinergic stimulation

In the present study we investigated the participation of central H1 and H2 histaminergic receptors in water intake induced by hyperosmolarity (evoked by intragastric salt load), by hypovolemia (promoted by the subcutaneous administration of polyethyleneglycol) and by the pharmacological stimulation of central cholinergic pathways by the muscarinic agonist carbachol in male Wistar rats. The data presented here show that the pharmacological blockade of central H1 histaminergic receptors by third ventricle injections of mepyramine significantly decreased water intake induced by hyperosmolarity, hypovolemia and by the intracerebroventricular injections of carbachol. On the other hand, the pharmacological blockade of central H2 histaminergic receptors by third ventricle injections of cimetidine significantly reduced water intake in hypovolemic and hyperosmotic animals, but failed to alter water intake induced by central cholinergic stimulation by carbachol. We conclude that H1 and H2 brain histaminergic receptors are involved in inducing thirst during hyperosmolarity and hypovolemia and that H1 histaminergic receptors located post-synaptically in relation to cholinergic pathways seem to be important in triggering drinking following central pharmacological cholinergic stimulation.     

Different thermal dependency of cutaneous sympathetic outflow to glabrous and hairy skin in humans

We investigated the effects of ambient temperature on the sudomotor and vasoconstrictor components of skin sympathetic nerve activity (SSNA). The sympathetic traffic was measured by simultaneous microneurographic recording from post-ganglionic nerve fibres in the tibial and the peroneal nerves. When the ambient temperature was raised from 25° C to 34° C, both sudomotor and vasoconstrictor components of SSNA were enhanced in the peroneal nerve but were suppressed in the tibial nerve. The sudomotor and vasoconstrictor sympathetic outflows were elevated in both nerves when the temperature was lowered from 34° C to 18° C. Our results suggested that the sudomotor and the vasoconstrictor components of SSNA are differently modulated by ambient temperature. The difference in sudomotor and vasoconstrictor components of SSNA in the tibial and the peroneal nerves at different ambient temperature may have been responsible for the differences observed in sweating and vasoconstriction in glabrous and hairy skin.     

Alteration of EEG activity of the hypothalamus by thermal stimulation of the spinal cord

Summary EEG activity of various parts of the hypothalamus was recorded in unanaesthetized guinea pigs during thermal stimulation of the spinal cord. In the anterior hypothalamus fast waves became more prominent when the spinal cord temperature (T _sc ) was raised from 40° to 42° C, resulting in an increase of the mean frequency by about 50%. The electrical activity remained unaffected whenT _sc was raised from 38° to 40° C. In the posterior hypothalamus, spinal cord heating from 39.5° to 42° C led to a decrease of the mean frequency by about 30%, while temperature changes from 38° to 39.5° C were less effective.Corresponding studies in cold-adapted animals showed that the EEG response to spinal cord heating is modified by thermal adaptation. In this group of animals electrical activity of the posterior hypothalamus could be influenced clearly by heating the spinal cord from 38° to 39.5° C, while a temperature change in this range was nearly ineffective in animals reared at 20° C.     

Antagonistic changes of gastric and colonic motility during selective thermal stimulation of thoracic and lumbosacral cords in anesthetized dogs

Changes in gastric and distal colonic motility evoked by thermal stimulation of the thoracic and lumbosacral cords, either individually or simultaneously, were investigated in spinal-intact dogs and in dogs spinalized at the cervical level.Simultaneous cooling of the thoracic and lumbosacral cords increased both gastric and colonic motility before and after spinalization. The direction of the responses evoked by simultaneous heating was the opposite, but only the decrease in gastric activity in the spinal-intact dog was significant.Selective cooling of the thoracic cord increased gastric motility, but decreased colonic motility before and after spinalization. Selective heating decreased gastric motility before and after spinalization, and increased colonic motility before spinalization.Selective cooling of the lumbosacral cord decreased gastric motility and increased colonic motility in spinal-intact dogs. No significant responses could be observed during selective heating in spinal-intact dogs. However, in spinalized dogs, the selective cooling and heating increased and decreased colonic motility respectively, while no significant change was observed in gastric motility during the cooling and the heating.It is concluded from the results that thermal stimulation of the spinal cord directly affects spinal functions which control gastrointestinal motility, and that there exists a mutual inhibitory interaction between the thoracic and lumbosacral innervation of the gastrointestinal tract.     

Initiating extension of the lower limbs in subjects with complete spinal cord injury by epidural lumbar cord stimulation

We provide evidence that the human spinal cord is able to respond to external afferent input and to generate a sustained extension of the lower extremities when isolated from brain control. The present study demonstrates that sustained, nonpatterned electrical stimulation of the lumbosacral cord—applied at a frequency in the range of 5–15 Hz and a strength above the thresholds for twitches in the thigh and leg muscles—can initiate and retain lower-limb extension in paraplegic subjects with a long history of complete spinal cord injury. We hypothesize that the induced extension is due to tonic input applied by the epidural stimulation to primary sensory afferents. The induced volleys elicit muscle twitches (posterior root muscle-reflex responses) at short and constant latency times and coactivate the configuration of the lumbosacral interneuronal network, presumably via collaterals of the primary sensory neurons and their connectivity with this network. We speculate that the volleys induced externally to the lumbosacral network at a frequency of 5–15 Hz initiate and retain an extension pattern generator organization. Once established, this organization would recruit a larger population of motor units in the hip and ankle extensor muscles as compared to the flexors, resulting in an extension movement of the lower limbs. In the electromyograms of the lower-limb muscle groups, such activity is reflected as a characteristic spatiotemporal pattern of compound motor-unit potentials.Abbreviations C Cervical - CMUP Compound motor-unit potential - EMG Potential - CNS Central nervous system - EMG Electromyography, electromyographic - H Hamstring - L Lumbar - MLR Mesencephalic locomotor region - PARA Paraspinal muscles - Q Quadriceps - S Sacral - SCI Spinal cord injury, spinal cord-injured - SCS Spinal cord stimulation - T Thoracic - TA Tibialis anterior - TS Triceps surae     

Neurogenic non-adrenergic cutaneous vasodilatation elicited by hypothalamic thermal stimulation in dogs

Hypothalamic heating in dogs with depleted peripheral adrenergic transmitter stores by means of chronic application of reserpine elicits increase of hindpaw blood flow. The vasodilator response is not affected by alpha- and beta-adrenergic or cholinergic blocking substances, nor by histamine-, or prostaglandin-antagonists. Dopamine and ergometrine produce cutaneous vasoconstriction which is antagonized or prevented by haloperidol. The hypothalamic vasodilator response is abolished after intra-arterial injection of haloperidol, after lumbar sympathetic chain section, or by high doses of hexamethonium. The results indicate neurogenic non-adrenergic control of skin blood flow in thermoregulation possibly acting through inhibition of dopaminergic vasoconstrictor mechanisms.     

Role of cGMP and cAMP in the hemodynamic response to intrathecal sildenafil administration

INTRODUCTION:

Results from our laboratory have demonstrated that intracerebroventricular administration of sildenafil to conscious rats promoted a noticeable increase in both lumbar sympathetic activity and heart rate, with no change in the mean arterial pressure. The intracerebroventricular administration of sildenafil may have produced the hemodynamic effects by activating sympathetic preganglionic neurons in the supraspinal regions and spinal cord. It is well documented that sildenafil increases intracellular cGMP levels by inhibiting phosphodiesterase type 5 and increases cAMP levels by inhibiting other phosphodiesterases.

OBJECTIVE:

To examine and compare, in conscious rats, the hemodynamic response following the intrathecal administration of sildenafil, 8-bromo-cGMP (an analog of cGMP), forskolin (an activator of adenylate cyclase), or dibutyryl-cAMP (an analog of cAMP) in order to elucidate the possible role of the sympathetic preganglionic neurons in the observed hemodynamic response.

RESULTS:

The hemodynamic responses observed following intrathecal administration of the studied drugs demonstrated the following: 1) sildenafil increased the mean arterial pressure and heart rate in a dose-dependent manner, 2) increasing doses of 8-bromo-cGMP did not alter the mean arterial pressure and heart rate, 3) forskolin did not affect the mean arterial pressure but did increase the heart rate and 4) dibutyryl-cAMP increased the mean arterial pressure and heart rate, similar to the effect observed following the intrathecal injection of the highest dose of sildenafil.

CONCLUSION:

Overall, the findings of the current study suggest that the cardiovascular response following the intrathecal administration of sildenafil to conscious rats involves the inhibition of phosphodiesterases other than phosphodiesterase type 5 that increase the cAMP level and the activation of sympathetic preganglionic neurons.     

The relationship between exercise work intervals and duration of exercise on lower extremity training induced by electrical stimulation in humans with spinal cord injuries

A group of 90 male paraplegics were studied to determine the optimal training protocol for isokinetic exercise induced by functional electrical stimulation of the quadriceps muscles. The parameters that were varied were the number of training sessions a week, the length of the training sessions each day, and the work-rest intervals in each training session. Training for 3 days a week for 30 min a day with 6 s of exercise and 6 s of rest proved the optimal protocol. Training for 5 days or for 1 day a week was not as effective in training strength or endurance. A combination of 50% work and 50% rest produced a much greater gain in strength and endurance than work:rest ratios of 66%:33% or 25%:75%. When training was conducted for 5 min, 15 min or 30 min each day, the greatest increase was found when the muscles were exercised for 30 min each day. While more variables need to be examined, this study has provided some initial guidelines for isokinetic training of humans using electrical stimulation. Accepted: 9 April 2000