Effects of stimulation of the vertebral nerve around the proximal vertebral artery on pupil and the autonomic nervous system--a contribution to pathophysiology of Powers' intermittent vertebral artery compression syndrome]

In order to elucidate the pathophysiology involved in Powers' intermittent vertebral artery compression syndrome, the author investigated sympathetic and parasympathetic changes produced by stimulation of nerves around the proximal vertebral artery (the vertebral nerve) in anesthetized and immobilized cats. These changes were observed mainly through pupillary changes, pulse and blood pressure, evoked potentials in the lateral horn of the upper thoracic cord (centrum ciliospinale), in the cervical sympathetic trunk, and in the short ciliary nerve. Electrical stimulation of vertebral nerve and local application of K ion around the vertebral artery produced stimulus-dependent ipsilateral mydriasis; when stimulation of higher strength was applied pronounced ipsilateral and mild contralateral mydriasis and hypertension occurred. Electrical stimulation of perivascular tissue around the subclavian artery proximal to origin of the vertebral artery showed ipsilateral mydriasis; while on stimulating the distal subclavian, the costcervical, the omocervical and the internal thoracic arteries did not show any pupillary response. Neuronal discharges in the lateral horn of upper thoracic cord and in the cervical sympathetic trunk showed stimulus-dependent increases on stimulating the vertebral nerve; while, inhibitory responses were observed in the short ciliary nerve formed by parasympathetic nerve fibers. From the data available, it seems likely that the stimulation of periarterial neural structure of the vertebral artery produced sympathetic excitatory as well as parasympathetic inhibitory neuronal discharges simultaneously may probably be derived from the integrating autonomic center in the hypothalamus.     

Gustatory-salivary reflex: neural activity of sympathetic and parasympathetic fibers innervating the submandibular gland of the hamster

Electrophysiological experiments were performed to clarify the neural control mechanisms subserving gustatory-salivary reflex in anesthetized and decerebrate hamsters. Efferent neural activities of postganglionic sympathetic and preganglionic parasympathetic fibers, innervating the submandibular gland, were recorded when taste stimuli were infused into the oral cavity. Neural activities of primary gustatory afferents were also recorded from the chorda tympani (innervating the anterior part of the tongue) and the glossopharyngeal nerve (innervating the posterior part of the tongue). The parasympathetic fibers showed a low rate of spontaneous discharges (about 0.3 Hz), and responded tonically in an excitatory manner to taste stimulation. The magnitude of parasympathetic activity was highly correlated with the magnitude of gustatory afferent responses of the chorda tympani rather than that of the glossopharyngeal nerve. On the other hand, the sympathetic fibers showed irregular burst discharges (1.5 burst/s), and the rate of burst discharges was increased in response to high concentrations of HCl (0.03 M) or NaCl (1 M) solutions. Deafferentation experiments suggest that the parasympathetic activity is mainly influenced by gustatory information via the chorda tympani, while the sympathetic activity can be evoked by both the chorda tympani and glossopharyngeal nerve.     

Influence of sympathetic fiber stimulation on conduction of excitation in the cat pterygopalatine ganglion]

Interaction between excitation passing through parasympathetic and sympathetic pathways was studied by recording of action potentials evoked in postganglionic nerves of the cat pterygopalatine ganglion by both testing stimuli applied to the greater superficial petrosal nerve and conditioning stimuli applied to cervical sympathetic nerve. Depression of synaptic transmission through the ganglion is shown to take place under stimulation of the cervical sympathetic nerve. The magnitude of such inhibition reached to 13 +/- 3%.     

Effects of electrical stimulation of autonomic nervous system on degranulation of von Ebner's gland acini

In a series of studies to understand interactions between taste sensation and salivary gland function, we are pursuing experiments to determine the autonomic nervous system control of von Ebner's lingual salivary glands. Electrical stimulation of the glossopharyngeal nerve, which contains the parasympathetic nerve supply to von Ebner's glands, caused a reduction in secretory granules of the glands in the rat. This depletion of granules could be blocked by prior administration of the parasympathetic antagonist, atropine. In contrast, electrical stimulation of the sympathetic nerve supply was ineffective in causing granule depletion in von Ebner's gland, but produced almost total degranulation in the parotid gland of the same animals. It is concluded that parasympathetic nerves exert the principal control over von Ebner's gland, acinar degranulation in the rat; this is compared with autonomic control of other salivary glands that have a dual peripheral control by parasympathetic and sympathetic innervation.     

A sympathetic projection from sacral paravertebral ganglia to the pelvic nerve and to postganglionic nerves on the surface of the urinary bladder and large intestine of the cat

Anatomical and electrophysiological experiments have demonstrated a prominent projection from the sacral sympathetic chain via the pelvic nerve to postganglionic nerves on the surface of the urinary bladder and the large intestine of the cat. Retrograde labeling studies revealed that the pelvic nerve, which is generally believed to carry primarily parasympathetic axons, has a considerable population of sympathetic fibers originating mainly from the S1-S3 paravertebral ganglia. The number of sympathetic neurons projecting to the pelvic nerve (2,100) was about 75% of that projecting to the pudendal nerve (2,900), a somatic nerve which would be expected to carry a large sympathetic fiber constituent. Sympathetic neurons projecting to the pudendal nerve were located primarily in the L6-S2 ganglia. Electrophysiological studies confirmed the presence of a sympathetic pathway from the paravertebral ganglia to the pelvic viscera. Electrical stimulation (thresholds 1.5-3 V) of the lumbar sympathetic chain evoked firing in the pelvic nerve and in postganglionic nerves on the surface of the colon and bladder at latencies of 60-150 msec. The responses were unaffected by cutting the chain one segment rostral to the site of stimulation, but were abolished by the administration of a ganglionic-blocking agent (tetraethylammonium). The responses on the colon and bladder postganglionic nerves were also abolished by transection of the pelvic nerve. The conduction velocity in the sympathetic postganglionic axons was approximately 1 m/second. In summary, these studies indicate that the pelvic nerve, like somatic nerves, receives a prominent projection from the sympathetic chain ganglia. The function of this sympathetic paravertebral pathway and its relationship with prevertebral innervation of the pelvic organs remains to be established.     

Reciprocal and non-reciprocal action of the vagal and sympathetic nerves innervating the heart

Simultaneous recordings were made from vagal and sympathetic fibers innervating the heart in dogs anesthetized with chloralose. Reciprocal relationship between the two autonomic nerves was clearly seen in the baroreceptor reflex. Stimulation of chemoreceptors, however, evoked non-reciprocal responses of the two nerves; at the onset of the chemoreceptor reflex cardiac vagal and sympathetic discharges both increased, then, as baroreceptors became excited due to a pressor response, sympathetic nerve activity suddenly decreased while vagal discharges remained high, indicating the appearance of the reciprocal action typifying the baroreceptor reflex. Decrease in ventilatory volume and a slight increase in end-expired CO2 level augmented greatly both vagal and sympathetic discharges. As the phrenic-locked activity of the two nerves (i.e. the activity in vagus nerve occurs only in the absence of phrenic bursts while sympathetic discharges increase with phrenic bursts) increased, the alternate discharges between the two nerves became more conspicuous and the heart rate fluctuated with the respiratory (phrenic) rhythm. Thus, strong reciprocity between vagus and sympathetic can result in an oscillatory heart rate. When ventilatory volume was increased, both nerve activities decreased below control level. Mild hypoxia had similar effects to hypercapnia though changes in nerve activity were greater. When coactivation of vagal and sympathetic nerve was produced in reflex action, changes in vagal discharges occurred earlier and faster than in the sympathetic fibers. The magnitude of change in vagus activity was also far greater. The elimination of afferents in the vagi, the aortic and sinus nerves reduced cardiac vagal activity greatly. However, discharges were still present and occurred between phrenic bursts, indicating that the vagal "tone" is maintained centrally as well as peripherally by input from receptors in the cardiovascular system. The physiological significance of reciprocal and non-reciprocal control of vagal and sympathetic nerves innervating the heart was discussed.     

Spinal cord representation of the micturition reflex

The spinal cord origin and peripheral pathways of the sensory and motor nerves to the urinary bladder were delineated in the cat by stimulating the appropriate nerves near the urinary bladder and recording from the dorsal and ventral rootlets near the spinal cord. The parasympathetic preganglionic neurons originated in the sacral segments of the spinal cord and reached the bladder by way of the pelvic nerve. The preganglionic parasympathetic perikarya to the urinary bladder were distributed over a length of approximately 1.5 segments, centered near the junction of segments S-2 and S-3 in cats with a median arrangement of the lumbosacral plexus. Conduction velocities in preganglionic parasympathetic fibers to the bladder ranged from 46 to 2 M/sec with a mean maximal velocity of 18.2 M/sec. The major sympathetic pathway to the bladder was in the hypogastric nerve. Preganglionic sympathetic fibers originated in the lumbar spinal cord and traveled through the caudal mesenteric ganglion and hypogastric nerve to the urinary bladder. There were both ipsilateral and contralateral preganglionic and afferent fibers in this pathway. The preganglionic sympathetic neurons originated in segments L-2 and L-5. They were usually distributed over approximately 2 full segments centered near the junction of L-3 and L-4 in cats with a median arrangement of the lumbosacral plexus. Neurons involved in the micturition reflex may extend from the rostral end of the L-2 segment to the caudal end of the S-3 segment. The sympathetic preganglionic neurons were usually separated from the somatic and parasympathetic columns by segments L-5 to L-7.     

Effect of cardiac vagal and sympathetic nerve activity on heart rate in rhythmic fluctuations

Beat-to-beat changes observed in cardiac vagal and sympathetic nerve activity and their effects on cardiac cycle length were studied during slow wave blood pressure and heart rate fluctuations (third order rhythm) and during respiratory sinus arrhythmia. Recordings were made from both nerves simultaneously in chloralose anesthetized and artificially ventilated dogs. During slow wave fluctuations in heart rate, a linear relationship was found to exist between the number of spikes per pulse interval recorded from vagal and sympathetic nerves and the length of pulse intervals. During respiratory sinus arrhythmia the time course of rhythmic changes in nerve activity and in cardiac cycle length was analyzed. Comparison of time courses indicated that vagal discharges affected the timing of not the following beat, but the one after; while the sympathetic effect was further delayed, affecting the third beat after the discharge. Baroreceptor stimulation, which resulted in lengthening the cardiac cycle, shifted this relationship by one cycle, i.e. vagal discharges affecting the occurrence of the following beat, while sympathetic discharges affecting the beat after. These results provide evidence for the conclusion that in dogs both vagal and sympathetic nerve activity contribute to the control of cardiac cycle length, however, with different time relations and effectiveness.     

Split medulla preparation in the cat: arterial chemoreceptor reflex and respiratory modulation of the renal sympathetic nerve activity

The study was undertaken in order to assess the changes in sympathetic output in a split medulla preparation of the cat which, as shown earlier, has impaired respiratory rhythm generation. The effects of medullary midsagittal sections on renal sympathetic nerve firing were investigated in chloralose anesthetized, paralyzed and artificially ventilated cats. Recordings of phrenic and recurrent laryngeal nerve activity served as indices of central respiratory rhythm generation. Sections, 5 mm deep from the dorsal medullary surface and extending 6 mm rostrally and 3 mm caudally to the obex, did not produce any significant changes in heart rate, blood pressure or tonic renal sympathetic nerve firing levels. They decreased or abolished, however, the respiratory rhythmicity in renal sympathetic nerve which paralleled the reduction of inspiratory discharges in phrenic and recurrent laryngeal nerves, and abolished the carotid body chemoreceptor-sympathetic reflex. The inspiratory activity remaining after the sections could still be enhanced by chemoreceptor stimulation. The inhibitory baroreceptor and pulmonary stretch receptor sympathetic reflexes, and the central excitatory effect of CO2 on renal sympathetic nerve firing were not altered. The effects of electrical stimulation within the midsagittal plane of the medulla have shown that descending pathways from the medullary inspiratory neurons (or their medullary collaterals) do not participate in the facilitation of spinal preganglionic neurons during inspiration and in relaying the pulmonary stretch receptor inhibitory sympathetic reflex. A region located close to the obex was identified from which excitatory responses in renal sympathetic nerves, compatible with the response obtained by carotid sinus nerve stimulation, could be evoked. It is concluded that a lesion in the midline of the lower medulla at the level of the obex selectively destroys cells or pathways which relay the carotid body chemoreceptor-sympathetic reflex.     

Effects of taste stimulation on the efferent activity of the autonomic nerves in the rat

Effects of taste stimulation on the efferent discharges in the pancreatic and hepatic branch of the vagus nerve, and those in the adrenal, pancreatic and hepatic branch of the splanchnic nerve, and the sympathetic nerve innervating interscapular brown adipose tissue, were observed in the anesthetized rat. Sweet taste stimulation with 5% glucose or 10% sucrose caused an increase in activity of pancreatic and hepatic branch of the vagus nerve and brown adipose tissue nerve, and a decrease in discharge rate of the adrenal, pancreatic and hepatic branch of the splanchnic nerve. Salty taste stimulation with 5% NaCl resulted in opposite effects in these nerves. Results suggest preabsorptive reflex control of visceral functions due to taste stimulation.     

颈髓电刺激增加脑血流的作用机制研究

目的 尽管颈髓电刺激（SCS）在许多动物实验中已被证实能增加脑血流,但其作用机理还不甚明了。本文将从脑血管的交感和副交感通路方面探讨SCS对脑血流的影响机理。方法 对SD大鼠给予SCS并用激光多普勒（LDF）实时记录脑血流。动物分成5组,对照组：不对神经纤维和神经节作任何手术处理;V1组：切断双侧鼻睫状神经及其副交感节后纤维;SCS组：切断双侧颈上神经节;V1＋SCG：切断双侧鼻睫状神经及其副交感节后纤维及双侧颈上神经节;假手术组：手术暴露双侧鼻睫状神经和其副交感节后纤维及双侧颈上神经节,但不切断神经纤维或神经节。结果 SCS时的LDF变化在对照组、V1和SCG组间没有显著性差异。但在V1＋SCG组中,SCS的升脑血流效应却被明显抑制了。结论 SCS的升脑血流效应可能是通过交感和副交感双重通路实现的。     

Modulation of parasympathetic neuron phenotype and function by sympathetic innervation

Selective sympathetic nerve dysfunction occurs during aging and in certain disease states. Here, we review findings concerning the effects of chronic sympathetic denervation on parasympathetic innervation to orbital target tissues in the adult rat. Long-term sympathetic denervation was induced by excising the ipsilateral superior cervical ganglion for 5-6 weeks prior to analyses. Following sympathectomy, pterygopalatine ganglion parasympathetic neurons show reduced nitric oxide synthase protein in their somata and projections to vascular targets. Laser Doppler measurements of ocular blood flow indicate that sympathectomy is also accompanied by reduced nitrergic vasodilatation. In the superior tarsal muscle of the eyelid, parasympathetic varicosities, normally, are distant to smooth muscle cells but make axo-axonal contacts with sympathetic nerves, consistent with physiological evidence showing only prejunctional inhibitory effects on sympathetically mediated smooth muscle contraction. Following sympathectomy, parasympathetic varicosities proliferate and closely appose smooth muscle cells, and this is accompanied by establishment of parasympathetic-smooth muscle excitatory neurotransmission. Many pterygopalatine parasympathetic neurons normally contain nerve growth factor (NGF) protein and express NGF mRNA. However, following chronic sympathectomy or elimination of sympathetic impulse activity, NGF mRNA and protein are markedly reduced, indicating that sympathetic neurotransmission enhances NGF expression in parasympathetic neurons. Together, these findings portray a striking dependency of parasympathetic neurons on sympathetic nerves to maintain normal phenotype and function. Sympathetic influences on parasympathetic neurons may be mediated, in part, through axo-axonal synapses. NGF synthesis and release by parasympathetic neurons may represent a molecular basis underlying the formation of these synapses, and up-regulation of NGF synthesis by sympathetic nerve activity may act to reinforce these associations.     

Spinal sympathoexcitatory pathways activated by stimulating fastigial nuclei,hypothalamus, and lower brain stem in cats

In anesthetized cats electrical stimulation of a fastigial (medial cerebellar) nucleus caused discharges in sympathetic nerves which were accompanied by cardiovascular system responses, including rise in arterial blood pressure, increased pulse pressure, and tachycardia. The pathways mediating the excitatory autonomic effects of fastigial origin descend bilaterally in the dorsolateral column of the spinal cord in the region between the lateral corticospinal tract and the central grey substance. Similar influences from the hypothalamus and medullary reticular substance are also mediated through fibers descending in the same region of spinal dorsolateral white matter. Local lesions in the spinal cord abolish the discharges in inferior cardiac, splanchnic, and renal nerves which could be evoked from all three sources, and the spontaneous activity of these sympathetic nerves was also reduced. The lesions did not alter intercostal nerve-evoked activity nor prevented its spreading to segments above or below the lesions.     

An analysis of the axon populations in the nerves to the pelvic viscera in the rat

The present study uses selective surgical ablations combined with electron microscopic analyses to determine the number of axons in yarious catagories in rat hypogastric, pelvic, and pudendal nerves, these being the nerves to the pelvic viscera in this animal. Unmyelinated fibers predominate in all of these nerves. One of the most significant findings is that the pelvic nerve contains almost as many postganglionic sympathetic fibers as the hypogastric nerve. Previous investigators thought that the pelvic nerve supplied the parasympathetic inflow and the hypogastric nerve the sympathetic inflow to the pelvic viscera. The finding that there is a sizable sympathetic component in the pelvic nerve negates this idea, at least for the rat, and presumably calls for a reevaluation of the syndromes that arise from pelvic as opposed to hypogastric nerve section. Other findings of interest are (1) that there are unmyelinated efferent axons in the pudendal nerve, indicating that the pudendal is not a typical somatic nerve, (2) that the hypogastric nerve has a very small sensory component, and (3) that there are fibers surviving in the distal stumps of all these nerves, particularly the pelvic and hypogastric nerves.     

Responses of hepatic glucose output to electro-acupuncture stimulation of the hindlimb in anaesthetized rats

Responses of hepatic glucose output (HGO) to electro-acupuncture (EA) stimulation of the hindlimb were investigated in anaesthetized rats, focusing on involvement of the somatic afferent and autonomic efferent nerves. HGO was measured with a microdialysis probe implanted into the left lateral lobe of the liver. Stainless steel needles with a diameter of 0.25 mm were inserted into the right tibialis anterior muscle and connected to an electrical stimulator. The EA stimulation was delivered for 10 min at 10 mA, 20 Hz. Atropine was injected in order to block the action of the parasympathetic nerves, whereas phentolamine and propranolol were injected in order to block the action of the sympathetic nerves. Furthermore, adrenal sympathetic nerves were crushed bilaterally to block the reflex secretion of adrenal medullary hormones. The EA stimulation significantly increased HGO for 20 min after the onset of stimulation. The increases of HGO were abolished by severing the femoral and sciatic nerves, demonstrating that the responses are elicited via activation of somatic afferent nerves. Furthermore, the increases were diminished after severance of the adrenal sympathetic nerves, which regulate catecholamine secretion from the adrenal medulla. The increases were totally abolished after pretreatment with phentolamine, an alpha-adrenergic blocker, and propranolol, a beta-adrenergic blocker. On the other hand, the increases of HGO in response to the EA stimulation were augmented after pretreatment with atropine, a muscarinic cholinergic blocker. The present results demonstrate that EA stimulation to a hindlimb can reflexly increase HGO via activation of somatic afferents and, thereby, sympathetic efferents, including sympathetic efferents to the adrenal medulla. The present results further show that the increases of HGO in responses to EA stimulation are simultaneously reflexly inhibited via the parasympathetic nerves.     

Sympathetic and parasympathetic interaction in vascular and secretory control of salivary glands in anaesthetised dogs

The present study was undertaken to examine sympathetic-parasympathetic interactions in the regulation of salivary gland function, with special reference to the possible role of the sympathetic cotransmitter neuropeptide Y (NPY). In dogs anaesthetised with pentobarbitone, electrical stimulation of the parasympathetic nerve to the submandibular gland evoked an increase in glandular blood flow and salivary secretion. Sympathetic nerve stimulation evoked a significant prolonged attenuation of vasodilator and secretory responses to subsequent parasympathetic stimulation. This attenuation was not significantly altered by alpha- and beta-adrenoceptor blockade. Systemic administration of the sympathetic cotransmitter, NPY, mimicked the effect of the sympathetic stimulation by significantly attenuating vasodilatation and salivary secretion. The NPY Y1 receptor agonist, [Leu31, Pro34]NPY and the specific NPY Y2 receptor agonist N-acetyl[Leu28, Leu31]NPY 24-36 both significantly attenuated the vasodilatation and salivary secretion evoked by stimulation of the parasympathetic nerve. The NPY Y1 receptor antagonist, GR231118 significantly antagonised the attenuation of vasodilatation caused by both sympathetic stimulation and the NPY Y1 receptor agonist. GR231118 also inhibited the pressor response of NPY. Intra-arterial injection of methacholine and stimulation of the parasympathetic nerve both caused local vasodilatation in the gland which was significantly attenuated by pretreatment with sympathetic stimulation or the NPY Y1 agonist. The NPY Y2-specific agonist did not attenuate methacholine-induced vasodilatation but did attenuate vasodilatation evoked by parasympathetic stimulation. The results indicate that NPY as a sympathetic cotransmitter may have a role in the regulation of vascular secretory function of salivary glands.     

The effect of intrahypothalamic injections of glucose on sympathetic efferent firing rate

Electrical stimulation of the ventromedial hypothalamus of anesthetized rats, produced an increase in temperature of brown adipose tissue. The magnitude of increase in temperature was linearly related to the frequency (Hz) of electrical stimulation of the hypothalamus. Microinjection of glucose into the ventromedial hypothalamus produced a dose-dependent increase in firing rate of the sympathetic nerves to brown adipose tissue, whereas comparable volumes of physiological saline had no effect. Destruction of neurons in the ventromedial hypothalamus with injections of kainic acid completely blocked the stimulatory effect of glucose on the firing rate of nerves to the brown adipose tissue. These studies support the hypothesis that glucose sensitive neurons in the ventromedial hypothalamus can directly modulate sympathetic nerves supplying brown adipose tissue.     

Evidence for central patterning of sympathetic discharge in kittens

Cervical sympathetic nerve discharges in kittens were examined using power spectral techniques to describe the frequency components of nerve activities and to obtain evidence of modulation by central rhythm generators. Peaks in sympathetic spectra appeared in the 4–11 Hz band; however, coherences between sympathetic nerves occured at 4–5 Hz, while that between sympathetic and phrenic nerves occurred at 8–9 Hz. These findings indicate modulation by sympathetic and inspiratory rhythm generators.     

Determinants of response of pial arteries to norepinephrine and sympathetic nerve stimulation.

Feline pial arteries larger than 100 mu in diameter constricted in response to cervical sympathetic nerve stimulation suggests or in response to topical application of norepinephrine. Smaller pial arteries were unresponsive to norepinephrine. This unresponsiveness persisted when norepinephrine was dissolved in CSF with high calcium ion concentration, or in CSF with both high calcium ion and zero magnesium ion concentration, or when it was dissolved in the acid fluid used by Wahl et al. and applied by constant infusion or by intermittent application. Comparison of the responses of the larger pial vessels to norepinephrine and to sympathetic nerve stimulation that maximal activation of sympathetic nerves achieves a concentration of released norepinephrine equal to 5.9 x 10(-6) M. The constriction of the larger pial vessels in response to sympathetic nerve stimulation could account for modest reductions in cerebral blood flow.     

Studies on the sympathetic efferent nerves of brown adipose tissue of lean and obese Zucker rats

Previous studies have suggested that the sympathetic tone to brown adipose tissue (BAT) is reduced in the genetically obese (fa/fa) rat. The following experiments were designed to examine with electrophysiological techniques the activity of the sympathetic nerve innervating the interscapular BAT. The spontaneous activity of the efferent nerves was reduced in the obese (fa/fa) rat compared with the lean control. The activity of the nerve showed a linear relationship with changes in core temperature in both genotypes. Electrical stimulation of the ventromedial hypothalamus resulted in similar heat increments in BAT temperature for lean and obese, but this was associated with a smaller increase in nerve firing in the obese rat. Intracerebroventricular administration of glucose enhanced the nerve activity, whereas 2-deoxy-D-glucose reduced the nerve activity in both lean and obese rats. These data suggest that the sympathetic tone is suppressed in the genetically obese rat, but the response to temperature and central glucose metabolism is intact.