Sympathetic Adrenergic Fibers Research Articles

Adrenergic control of functional characteristics of the cardiovascular system in the South American rattlesnake, Crotalus durissus

In squamate reptiles, extensive innervation of the heart and vascular beds allows for continuous modulation of the cardiovascular system by the autonomic nervous system. The systemic vasculature is the main target of excitatory sympathetic adrenergic fibers, while the pulmonary circulation has been described as less responsive to both nervous and humoral modulators. However, histochemical evidence has demonstrated the presence of adrenergic fibers in pulmonary circulation. Besides, reduced responsiveness is intriguing since the balance of regulation between systemic and pulmonary vascular circuits has critical hemodynamic implications in animals with an undivided ventricle and consequent cardiovascular shunts. The present study investigated the role and functional relevance of α and β-adrenergic stimulation in regulating systemic and mainly the pulmonary circulations in a decerebrate, autonomically responsive rattlesnake preparation. The use of the decerebrate preparation allowed us to observe a new diverse functional modulation of vascular beds and the heart. In resting snakes, the pulmonary vasculature is less reactive to adrenergic agonists at 25 °C. However, the β-adrenergic tone is relevant for modulating resting peripheral pulmonary conductance, while both α- and β-adrenergic tones are relevant for the systemic circuit. Active dynamic modulation of both pulmonary compliance and conductance effectively counterbalances alterations in the systemic circulation to maintain the R-L shunt pattern. Furthermore, we suggest that despite the great attention given to cardiac adjustments, vascular modulation is sufficient to support the hemodynamic adjustments needed to control blood pressure.

The autonomic innervation of hairy skin in humans: an in vivo confocal study

The autonomic innervation of the skin includes different subsets of adrenergic and cholinergic fibers both in humans and animals. The corresponding chemical code is complex and often difficult to ascertain. Accordingly, a detailed histochemical description of skin autonomic fiber subtypes is lacking in humans. To characterize skin autonomic nerve subtypes may help to better understand the selective damage of specific skin autonomic fibers affecting human diseases such as the adrenergic fibers directed to skin vessels in Parkinson’s disease or the cholinergic sudomotor fibers in Ross Syndrome. The present study aimed at characterizing subtypes of autonomic fibers in relation to their target organs by means of an immunofluorescent technique and confocal microscopy. We studied 8 healthy subjects (5 males and 3 females) aged 45 ± 2 (mean ± SE) years without predisposing causes for peripheral neuropathy or autonomic disorders. They underwent skin biopsy from proximal (thigh) and distal (leg) hairy skin. A combination of adrenergic (i.e. tyrosine-hydroxylase- TH and dopamine beta-hydroxylase- DbH) and cholinergic (vesicular acetylcholine transporter- VACHT) autonomic markers and neuropeptidergic (i.e. neuropeptide Y- NPY, calcitonin gene-related peptide- CGRP, substance P- SP, and vasoactive intestinal peptide- VIP) markers were used to characterize skin autonomic fibers. The analysed skin autonomic structures included: 58 sweat glands, 91 skin arterioles and 47 arrector pili muscles. Our results showed that all skin structures presented a sympathetic adrenergic but also cholinergic innervation although in different proportions. Sympathetic adrenergic fibers were particularly abundant around arterioles and arrector pili muscles whereas sympathetic cholinergic fibers were mainly found around sweat glands. Neuropeptides were differently expressed in sympathetic fibers: NPY were found in sympathetic adrenergic fibers around skin arterioles and very seldom sweat glands but not in adrenergic fibers of arrector pili muscles. By contrast CGRP, SP and VIP were expressed in sympathetic cholinergic fibers. Cholinergic fibers expressing CGRP, SP or VIP without TH or DbH staining were found in arterioles and arrector pili muscles and they likely represent parasympathetic fibers. In addition, all skin structures contained a small subset of neuropeptidergic fibers devoid of adrenergic and cholinergic markers with a likely sensory function. No major differences were found between males and females and proximal and distal sites. In summary hairy skin contains sympathetic adrenergic and cholinergic fibers differently distributed around skin structures with a specific distribution of neuropeptides. The autonomic skin innervation also contains a small amount of fibers, likely to be parasympathetic and sensory.

Spatiotemporal Regulation of Hematopoietic Stem Cell Niches By Dual Cholinergic Signaling

Hematopoietic stem cells (HSCs) are known to be heterogeneous, but it is unclear whether, or how, different bone marrow (BM) microenvironments can imprint distinct HSC states. In the BM, quiescent HSCs have been found enriched in endosteal niches, whereas activated HSCs traffic in and out the BM through sinusoids localized further from bone. However, how these separate niches are integrally regulated to maintain BM homeostasis remains largely unknown. We have shown previously that sympathetic adrenergic nerve terminals innervating nestin+ mesenchymal stem cells (MSCs) regulate HSC egress from BM to circulation (Méndez-Ferrer S et al, Nature 2008 and 2010). This regulatory network is required to control HSC proliferation and migration, since its damage caused by mutated HSCs can lead to the manifestation of diseases such as myeloproliferative neoplasms and its protection can block the progression of these disorders (Arranz L et al, Nature 2014). Here we aimed to study the possible cooperation of both branches of the autonomic nervous system, the parasympathetic and the sympathetic nervous systems, which have antagonistic actions in other systems, in HSC regulation in endosteal and sinusoidal niches. We describe for the first time different cholinergic neural signals derived from both autonomic branches that regulate spatially and temporally distinct BM HSC niches. We used mice deficient in cholinergic nerve fibers (secreting acethylcholine, the main postsynaptic neurotransmitter of the parasympathetic nervous system), due to the lack of the neurturin receptor Gfrα2, a member of the glial-cell-derived family of neurotrophic factors (Rossi J et al. Neuron 1999). We found that Gfrα2-/- mice exhibited a circadian-specific defect in HSC traffic. Parasympathetic deficiency caused exacerbated sympathetic tone, manifested by ~2-fold increased BM sympathetic adrenergic fibers and nocturnal urine norepinephrine. Circulating HSCs, measured by long-term competitive repopulating assays, were 3-fold higher in Gfrα2-/- mice only during the resting period, and this was rescued by deletion of the β3-adrenergic-receptor. Therefore, systemic parasympathetic cholinergic signals antagonize BM sympathetic adrenergic activity during the resting phase, contributing to β3-adrenergic-receptor-orchestrated circadian HSC traffic through sinusoidal niches. On the other hand, sympathetic cholinergic nerve fibers, described here for the first time in the BM and running along Haversian canals of bone, regulate HSC maintenance and quiescence in endosteal niches. In neonatal mice, we found that some endosteal sympathetic nerve fibers, sensitive to chemical sympathectomy by 6-hydroxydopamine, switch from catecholaminergic to cholinergic fate and help direct developmental HSC migration to BM. This migration, dependent in perinatal life on Cxcl12 produced by BM nestin+ MSCs (Isern et al, eLife 2014), was impaired in Gfrα2-/- mice, which exhibited one week after birth a reversible ~40% reduction in BM HSCs, associated with the lack of BM sympathetic cholinergic fibers. In adult mice, these sympathetic cholinergic fibers activate nicotinic receptors and induce Cxcl12 expression in bone-associated nestin+ MSCs, an effect reproduced in vitro with the MS-5 stromal cell line. Cxcl12 expression was 2.5-fold higher in Nes-GFP+ cells associated with the bone, compared with those that were not, and was 4-fold lower in Gfrα2-/- Nes-GFP+ cells localized only in the endosteal BM. Concomitantly, Gfrα2-/- mice exhibited reduced allocation of quiescent HSPCs in the endosteal BM, compared with control mice, in which the HSPC fraction in the G0 cell cycle phase was 2-fold higher in the endosteal than in non-endosteal BM. Moreover, HSCs from Gfrα2-/- mice showed increased proliferation, even 6 months after transplantation into secondary wild-type recipients. As a result, Gfrα2-/- mice exhibit accelerated hematopoietic recovery after myeloablation, a phenotype mimicked by mice deficient in the α7-nicotinic receptor. Increased HSC proliferation was associated with loss of self-renewal, since bone-associated HSCs from Gfrα2-/- mice exhibited 50% reduced reconstituting capacity and myeloid potential 24 weeks after competitive transplantation into wild-type recipients. Thus, both branches of the autonomic nervous system regulate HSC maintenance and function in temporally and spatially separate niches. DisclosuresNo relevant conflicts of interest to declare.

The quantification of cutaneous autonomic pilomotor innervation

Background: Our objective in this study is to define the topography of pilomotor nerve fiber density PNFD) in clinically relevant sites, to demonstrate the effectiveness of both dopamine β-hydroxylase (DβH) and tyrosine hydroxylase (TH) to stain for sympathetic adrenergic fibers, and determine the pilomotor nerve fiber density (PNFD) in healthy control subjects and individuals with diabetes using standard light microscopy PGP stained tissue sections.

Inhibition of sympathetic cholinergic vasodilatation by a selective NPY Y 2 receptor agonist in the gracilis muscle of anaesthetised dogs

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 Y 1 receptor NPY causes constriction directly in addition to potentiating other vasoconstrictor agents. NPY acting at the prejuctional, or Y 2 receptor, inhibits the release of neurotransmitter from autonomic nerve terminals. In these experiments we used the selective Y 2 receptor agonist N-acetyl[Leu 28, Leu 31]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[Leu 28, Leu 31]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 Y 2 agonist N-acetyl[Leu 28, Leu 31]NPY24–36. This dilatation was abolished by atropine, confirming its cholinergic nature. N-Acetyl[Leu 28, Leu 31]NPY24–36 was found to have no effect on nerve evoked vasoconstriction. The results demonstrate a NPY Y 2-receptor mediated inhibition of nerve evoked sympathetic cholinergic vasodilatation but not of sympathetic vasoconstriction.

An immunohistochemical study of the innervation of the large intestine of the toad (Bufo marinus).

The distribution of intrinsic enteric neurons and extrinsic autonomic and sensory neurons in the large intestine of the toad, Bufo marinus, was examined using immunohistochemistry and glyoxylic acid-induced fluorescence. Three populations of extrinsic nerves were found: unipolar neurons with morphology and location typical of parasympathetic postganglionic neurons containing immunoreactivity to galanin, somatostatin and 5-hydroxytryptamine were present in longitudinally running nerve trunks in the posterior large intestine and projected to the muscle layers and myenteric plexus throughout the large intestine. Sympathetic adrenergic fibres supplied a dense innervation to the circular muscle layer, myenteric plexus and blood vessels. Axons containing colocalized calcitonin gene-related peptide immunoreactivity and substance P immunoreactivity distributed to all layers of the large intestine and are thought to be axons of primary afferent neurons. Five populations of enteric neurons were found. These contained immunoreactivity to vasoactive intestinal peptide, which distributed to all layers of the large intestine; galanin/vasoactive intestinal peptide, which projected to the submucosa and mucosa; calcitonin gene-related peptide/vasoactive intestinal peptide, which supplied the circular muscle, submucosa and mucosa; galanin, which projected to the submucosa and mucosa; and enkephalin, which supplied the circular muscle layer.

Localization of sympathetic postganglionic neurons innervating the femoral-saphenous vein in cats

Physiological and histochemical studies have suggested that the limb veins are innervated by sympathetic adrenergic fibers. In the present experiment, horseradish peroxidase (HRP) was used as a retrograde tracer to identify and localize the sympathetic postganglionic neurons that innervate the femoral-saphenous vein in cats. In anesthetized cats, HRP was applied perivascularly on a femoral and a saphenous vein segment (4–8 mm in length for each segment) to allow uptake into the nerve endings. The sympathetic chains on both sides were dissected after the animal was sacrificed and fixed 60 h following the HRP application. Histological examination on serial section was done to count the HRP-labeled neurons in each sympathetic ganglion from L 1 to S 1. In 10 cats, the total number of HRP neurons amounted to 8569. Most neurons arose from L 3 (47%) and then L 4 (31%). The number of neurons became progressively decreasing towards both ends of the sympathetic chain. Few neurons (less than 2% of the total) were discovered in the contralateral sympathetic ganglia. In each ganglion, the distribution of HRP neurons appeared to be scattering. Our findings provide anatomical evidence to support that the femoral-saphenous vein of the cat was innervated by the sympathetic efferent fibers. The main origins of these neurons are the third and fourth lumbar sympathetic ganglia.

Vagal mechanisms controlling serotonin release from the gastrointestinal tract and pyloric motor function.

This chapter focuses on investigations of two mechanisms controlled by the vagal nerve; serotonin (5-HT) release from the small intestine and pyloric motor function. Morphological, physiological, pharmacological and biochemical methods were combined in these studies. 5-HT is mainly stored in enterochromaffin cells (EC), but is present also in mast cells and nerve terminals of the gut, as observed by immunocytochemistry. Vagal nerve stimulation causes a release of 5-HT from EC to the portal circulation and to the gut lumen. Morphological evidence for the endoluminal release of 5-HT was obtained by autoradiography and immunofluorescence. The 5-HT release from EC is mediated by a beta-adrenoceptor mechanism via sympathetic adrenergic fibers in the vagal nerve, originating from sympathetic ganglia, e.g. the superior cervical ganglion. This vagal adrenergic pathway was studied by fluorescence microscopy and retrograde tracing of horseradish peroxidase. The vagal peptidergic (nonadrenergic, noncholinergic) control of pyloric motor function was studied in chloralosed cats by means of an in vivo model, where changes of an applied flow of body-warm saline through the pylorus were recorded. Also, gastric volume changes were monitored. By means of immunofluorescence the presence of VIP-, enkephalin (ENK)- and substance P (SP)-like immunoreactivity was demonstrated in pyloric neurons and in the vagal nerve. Physiological evidence for a vagal VIPergic relaxatory mechanism was obtained, while ENK-neurons seem to mediate the vagally induced pyloric contraction, prevented by naloxone pretreatment. SP may mediate part of the vagally induced pyloric and gastric contraction, the latter probably via axon collaterals on final cholinergic neurons. ENKergic and SPergic vagal contractile mechanisms seem to be additive for the pylorus.

Local blood flow regulation in normotensive man during prolonged treatment with propranolol.

The influence of propranolol on blood flow in peripheral tissues was studied in 10 normotensive subjects. Adequacy of beta-blockade was ascertained by an ergometric test. Perfusion of the subcutaneous tissue and skeletal muscle was measured by the local 133Xe-washout technique. The arteriolar dilatation underlying the autoregulatory response to a decrease in arterial perfusion pressurehead was not affected by beta-blockade. Propranolol did not change the magnitude of arteriolar constriction elicited by the local sympathetic veno-arteriolar reflex. Thus, the locally induced increase in the discharge rate along the peripheral sympathetic adrenergic fibres did not lead to measurable change in beta-receptor activity. The present results indicate that local bloodflow regulatory mechanisms are not affected by propranolol. They also indicate that the direct peripheral effects of propranolol are of no clinical importance in normotensive subjects in the supine position, when the general activity in the sympathetic nervous system is low.

Seizures and related epileptiform activity in hippocampus transplanted to the anterior chamber of the eye: Modulation by cholinergic and adrenergic input

Transplants of rat hippocampus into the anterior chamber of the eye of a host animal were used to assess the effects of cholinergic and adrenergic neuronal inputs on the generation and duration of seizure activity. Cholinomimetics initiated both seizures and hypersynchronous neuronal activity in the transplants. Cyclic guanosine monophosphate (GMP) derivatives and isobutyl methylxanthine elicited similar changes. Reflex activation of the cholinergic parasympathetic input to the iris and transplant by illumination of the ipsilateral retina also induced seizures or increased the rate of penicillin-induced interictal spike discharge. Application of beta-adrenergic agonists inhibited interictal spikes and paroxysmal depolarizing shifts induced by penicillin. Fluorescence histochemical studies showed that host sympathetic adrenergic fibers derived from the ground plexus of the iris invaded the transplant to form fine varicose nerve terminals. Activation of these adrenergic afferents to the transplant diminished both the amplitude and frequency of penicillin-induced epileptiform activity. Epileptiform activity in hippocampal occular transplants is strongly modulated by cholinergic and adrenergic neuronal inputs, with the former exerting a facilatory influence and the latter, an inhibitory effect.

Intrinsic regulation of blood flow in adipose tissue.

Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called autoregulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an autoregulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g-min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue. Following total ischemia all experiments showed a period with reactive hyperemia, and both duration of hyperemia and excess flow was related to the duration of the ischemia. This response therefore seems more resistant to the experimental procedure, while autoregulation of blood flow to lowered pressure is more susceptible to surgical exposure of the tissue. During elevation of arterial perfusion pressure blood flow in the isolated tissue showed a transient increase and then almost returned to the level during normotension, indicating an elevated vascular resistance. Raising of venous pressure elicited vasoconstriction with pronounced flow reduction. These two reactions may be important for local regulation of blood flow in subcutaneous tissue during orthostatic changes in arterial and venous pressure. It is concluded that the response in adipose tissue to changes in arterial pressure (autoregulation), venous pressure and total ischemia appear to be elicited by different mechanisms.

Local Reflex in Microcirculation in Human Subcutaneous Tissue

The effect of changes in transmural pressure in the vessles of the extremities on blood flow in subcutaneous adipose tissue were investigated in three healthy subjects. Changes in transmural pressure were obtained either by postural changes of a limb, by locally induced subatmospheric pressure, or be venous stasis. Blood flow in subcutaneous tissue was measured 10 cm distal to the fibular head and at the lateral malleolus in the leg, or in the distal part of the forearm by the local 133Xenon washout technique. When transmural pressure increased 25 mmHg or more, blood flow decreased about 50 per cent due to an increase in vascular resconstrictor response to increase in transmural pressure could be blocked by infiltrating the area under study with phentolamine or lidocaine or by induced counterpressure. In these cases blood flow remained constant. The findings indicate that the vasoconstrictor response to increase in transmural pressure of 25 mmHg or more is due to a local nervous mechanism involving adrenergic nerves. The receptors are presumably stretch receptors placed in the small veins. The effector site is probably the arterioles. When the vasoconstrictor response is blocked, autoregulation of blood flow in subcutaneous tissue, i.e. maintenance of constant blood flow during changes in perfusion pressure head or during changes in transmural pressure, is revealed. The vasoconstrictor response to increase in transmural pressure will counteract an increase in transmural pressure in the exchange vessles and thereby act as an edema protecting factor.

Effects of drugs and nerve stimulation on the spleen and arteries of two species of dogfish, Scyliorhinus canicula and Squalus acanthias.

The effects of drugs and nerve stimulation on the spleen of 2 species of dogfish have been examined by experiments with perfused spleens and isolated spleen and artery strips. Adrenaline, noradrenaline and phenylephrine, acting via alpha adrenoceptors, constrict the perfused spleen of both species, thereby releasing erythrocytes, and contract the isolated spleen and artery strips. Phenotolamine competitively antagonizes the excitatory effects of adrenergic agonists. The responses of the spleen to acetylcholine are very irregular, and a rapid desensitization makes evaluation of the mode of action of this drug difficult. In the artery strips acetylcholine produces a dose-dependent contraction. Fluorescent histochemistry reveals well developed adrenergic innervation of the arteries, and a few adrenergic terminals in the spleen. Stimulation of splenic nerves produces normally splenoconstriction in Squalus, which can be blocked by phentolamine but not by atropine. The nervous control of the Scyliorhinus spleen seems to be poor or lacking. It is concluded that the dogfish spleen, and maybe also the arteries, are to a large extent controlled by circulating catecholamines and (in Squalus) also by sympathetic adrenergic fibres.

Formation of a functional adrenergic input to intraocular cerebellar grafts: ingrowth of inhibitory sympathetic fibers.

The intraocular transplantation technique was used to study the ingrowth of peripheral sympathetic adrenergic nerves from the iris into transplants of fetal rat cerebellum, and the possible function of these nerves. The transplants, grown in oculo for one-half to eight months, were analyzed by fluorescence histochemistry and electrophysiological techniques. Peripheral sympathetic adrenergic fibers from the iris were able to grow into the cerebellar transplants and arborize in a pattern similar to that in situ, appearing in all three cortical layers and the noncortical areas of the transplants. The density of visible nerves without pretreatment and after preincubation in 10(-6) or 10(-5) M alpha-methylnorepinephrine was comparable to mature rat cerebellum. The spontaneous discharge of the Purkinje cells in oculo was inhibited by microiontophoresis of norepinephrine (NE) and amphetamine in sympathetically innervated, as well as sympathectomized transplants denervated by ganglionectomy. The NE response was blocked by the adrenergic beta-receptor blocker MJ-1999. GABA also inhibited the Purkinje cell activity while glutamate accelerated the discharge. Parenteral amphetamine inhibited Purkinje cell activity in sympathetically innervated transplants, but was ineffective in denervated transplants. The Purkinje cell spontaneous activity was inhibited by electrical stimulation of the NE fiber input through the cervical sympathetic trunk. This inhibition could be antagonized by parenteral reserpine or the beta-adrenergic antagonist propranolol. The responses of the Purkinje cells within the transplants to drugs and transmitters mimic those of the adult rat in situ. In view of the fluorescence histochemical evidence for an ingrowth of peripheral sympathetic adrenergic fibers into the cerebellar transplants, and the results of stimulating the sympathetic trunk, it is suggested that peripheral adrenergic fibers may be able to establish functional connections with the Purkinje cells similar to the cerebellar adrenergic synapses normally formed in situ by fibers from the locus coeruleus.

Reflex respiratory and cardiovascular effects of stimulation of receptors in the nose of the dog

1. In forty-one out of forty-seven dogs under chloralose-urethane or Nembutal anaesthesia, mechanical stimulation of the nasal mucous membrane caused a reduction or inhibition of respiration, bradycardia, variable changes of arterial blood pressure, and a small rise in venous pressure.2. Simultaneous measurements of arterial and venous pressures, and also of blood flow in various arteries by means of an electromagnetic flowmeter indicate that the calculated vascular resistance increases in the intact limb, muscle, and skin, and the vascular beds of the vertebral, superior mesenteric, renal and splenic arteries. No changes in vascular resistance occur in the common carotid circulation.3. Evidence is presented that the increase in vascular resistance is due to vasoconstriction, and occurs in the absence of changes in pulmonary ventilation.4. Stimulation of the nasal mucous membrane causes a reduction in volume of the spleen.5. The respiratory and cardiovascular responses are reflex in nature, being abolished by the application of a local anaesthetic to the nose or by combined division of the maxillary and ethmoidal branches of the trigeminal nerves. The cardiac response is mediated largely by the vagus nerves, and the vascular responses by sympathetic adrenergic fibres.6. Cessation of the stimulus to the nose not infrequently results in the following temporary after-effects: hyperventilation, tachycardia, hypertension, and vasodilatation in the intact limb and in muscle.

Adrenergic innervation of the oesophagus in the cat (Felis domestica) and Rhesus monkey (Macacus rhesus).

The distribution of monoamines in the pharynx and oesophagus of the rhesus monkey (Macacus rhesus) and the cat (Felis domestica) was investigated by means of fluorescence microscopical and chemical methods. Fluorimetric determinations reveal the presence of varying amounts of noradrenaline in the pharynx and oesophagus of the rhesus monkey. The lowest amount (0.05 (μg/g) was found in the lower part of the oesophagus, the so-called sphincter-segment. The middle and upper part of the oesophagus contain medium amounts of noradrenaline (0.06–0.09 μg) whereas the highest concentration was detected in the pharynx (0.14 (μg/g). Neither dopamine nor adrenaline occurred in the tissue pieces analyzed. Fluorescence microscopically noradrenaline was found to be located in varicose intramural nerve fibre plexus which innervate mucous glands and blood vessels in the pharynx of both species. In the rhesus monkey, the lamina muscularis mucosae of all parts of the oesophagus is supplied by a well developed noradrenergic ground-plexus. Preterminal and terminal varicose nerve fibres are distributed in myenteric and submucous ganglia of the oesophagus; the number of such ganglia decreases towards the lower segment. The density of the adrenergic innervation is higher in myenteric when compared to submucous ganglia. The arrangement of the intraganglionic terminals suggests that both axosomatic and axodendritic contacts occur in Auerbach's ganglia whereas axodendritic contacts seem to predominate in Meissner's ganglia. Myenteric ganglia situated close to the submucosa as well as true submucous ganglia may be occasionally seen to be traversed by faintly fluorescent non-varicosed fibres which do not establish any synaptic contacts. The fluorescence intensity of intraganglionic varicosities varies considerably; accordingly the transmitter content of individual varicosities seems to be very variable. The adrenergic innervation of the lamina muscularis is restricted to single contorted fibres being sparsely distributed throughout the longitudinal smooth muscle layer. The circularly arranged smooth musculature of the sphincter-segment lacks an adrenergic nerve supply. The vagus nerve carries sympathetic adrenergic fibres to the lower oesophagus and the cardia. Species differences between the innervation pattern in rhesus monkeys and cats are outlined: No adrenergically innervated ganglia occur in the submucosa of the cat. However, part of the myenteric ganglia in cats exhibit an adrenergic innervation pattern similar to that seen in submucous ganglia of the rhesus monkey. They might therefore be regarded as morphologically equivalent to the plexus submucosus which is, however, present in the whole gut. The density of the noradrenergic ground-plexus in the muscularis mucosae of the cat's oesophagus is less than that of the corresponding plexus in rhesus monkeys. The influence of noradrenaline upon the smooth musculature and the neurons from myenteric as well as submucous ganglia is discussed. From the point of view of the adrenergic innervation there is no structure corresponding to the sphincterlike lower oesophageal segment.

Development of sympathetic adrenergic fibres.

Development of sympathetic adrenergic fibres.

The effect on muscle glycogen of shock due to spinal cord destruction and of haemorrhagic shock with peripheral denervation.

In rats with shock due to spinal cord destruction (pithed rats) and severe terminal hypoglycaemia muscle glycogen remains normal, whereas it falls in shock due to other causes. To explain this difference the role of denervation on muscle glycogen was investigated.In rats with destruction of the lower part of the spinal cord, the denervated hindlimbs showed a higher muscle glycogen concentration than the normally innervated forelimbs, in spite of severe shock. In other experiments is was found that in haemorrhagic shock one‐sided proximal interruption of the femoral nerve resulted in a higher glycogen concentration in the rectus femoris than on the other sham‐operated side. However, the same differences were found also in the gastrocnemius, whose motor nerve fibres were intact. Blockade with phenoxybenzamine prior to haemorrhagic shock abolished this difference between the denervated and intact limb completely. It is concluded that a section of the femoral nerve interrupts accompanying sympathetic adrenergic fibres to the hindlimb, thereby preventing vasoconstriction and reducing tissue hypoxia during haemorrhagic shock. The normal muscle glycogen concentration during severe spinal shock must be explained by a failure of reflexogenic hyperactivity of the sympathetic nervous vasomotor system.In studies on the effects of peripheral denervation, the possible role of interruption of accompanying autonomic nervous fibres is often neglected.