Adrenergic and cholinergic innervation of the prostate in laboratory animals

The prostate innervation has been studied in 50 white rats, 12 rabbits, 12 guinea pigs, 6 cats and 6 dogs. Together with the impregnation techniques, Karnovsky-Roots method has been applied, for revealing cholinergic components, and the incubation method in 2% solution of glyoxylic acid, for revealing adrenergic nervous structures. Density of adrenergic and cholinergic nervous plexuses has been estimated by means of the planimetric point method. The prostate of the laboratory animals possesses well manifested adrenergic and cholinergic nervous plexuses. The organ's alveolus and ducts are covered with adrenergic and cholinergic fibers, however, the relative density of the cholinergic plexuses is less than that of the adrenergic ones. The guinea pig prostate is the most richly supplied with the adrenergic nervous plexuses, and the rabbit prostate--with the cholinergic nervous plexuses.     

Sources of the innervation of the carotid reflexogenic zone in representative reptiles

The investigation is dedicated to study sources of the carotid reflexogenic zone innervation in 43 tortoises (Testudo horsfieldi and Emys orbicularis). In 7 tortoises fine preparation of the vessels and nerves of the cervical area after V. P. Vorob'ev has been performed. In 13 animals descending branch of the glossopharyngeal nerve has been resected. In 4--the caudal ganglion of this nerve and in 9 tortoises the caudal ganglion of the vagus nerve have been resected. In 10 tortoises adrenergic nervous plexuses are studied after Falck-Govyrin method, and cholinergic ones--after Karnovsky-Roots. As demonstrate anatomical investigations, to the carotid reflexogenic zone of the tortoises, situating in the area of the common carotid artery base, the branches of the glossopharyngeal and of the vagus nerve approach. The experiments with resection of these nervous conductors demonstrate that by the end of 3 days after the operation myelin nervous fibers of various thickness are at the stage of granular decay. Cholinergic and adrenergic nervous fibers and plexuses are revealed histochemically in the carotid zone.     

Partial degeneration of autonomic nerves of the heart of methotrexate-treated guinea pigs

In the present investigation partial degeneration of adrenergic and cholinergic nerves of the heart of guinea pigs following methotrexate treatment has been reported. No appreciable change was observed in the autonomic nerve fibres after 3 days of treatment. However, after prolonged treatment some nerve fibres showed signs of degeneration and a few adrenergic and cholinergic nerve fibres had disappeared.     

Morphofunctional changes in the adrenergic innervation of the major cerebral arteries during bilateral electrostimulation of the locus coeruleus

The intramural adrenergic nervous apparatus of cerebral arteries was studied in adult rabbits after 3-10 sessions of electrical stimulation of locus coeruleus. The activity of nerve structures was determined by estimating the density of adrenergic perivascular plexuses and by semi-quantitative cytophotometry of changes in the catecholamine content of nerve varicosities. The stimulation was followed by a 28.2 +/- 1.5% increase in adrenergic innervation density. while catecholamine content in perivascular nerve structures displayed a tendency to decrease. The problem of central effects on cerebral blood flow autoregulation is discussed.     

Adrenergic and cholinergic components of the innervation of the arteries of the base of the bird brain

By means of Falck's and Koelle's methods adrenergic and cholinergic structures were studied in the arteries in the cerebral basis of blue rock pigeons and of hens, white leghorn stock. The number of nerve transmitters was estimated per 1 mm2 of the vessel surface. The arteries of the basis in pigeon brain are surrounded with developed adrenergic and cholinergic nerve plexuses, their density decreasing in the following order: nasal branch of the internal carotid artery, middle, nasal cerebral and basilar arteries. A little more cholinergic transmitters occur on the middle cerebral artery, while on the other vessels, concentration of cholinergic and adrenergic fibers is equal. In hens, the density in the arrangement of adrenergic nerve transmitters is higher in the nasal branch of the internal carotid and in the nasal cerebral arteries than in the basilar artery. At the same time, chromaffin cells forming numerous conglomerations in some places are found on the latter. In pigeons, the density of adrenergic fibers arrangement on the arteries of the cerebral basis is higher than in hens.     

Histofluorescence and histochemical analysis of adrenergic and cholinergic innervation of the lungs in burns

Neurohistochemical methods were applied to study adrenergic and cholinergic nervous structures of pulmonary tissue in 30 patients aged 14-82 who had died of burn disease at various stages of its progress (shock, toxemia, septic toxemia). Autopsies performed within 4 hours after the patients' death evidenced mediators depletion in perivascular and peribronchial plexuses as well as intensive luminescence of nervous fibers considered as compensatory adaptation. There was cholinesterase hypoactivity in cholinergic plexuses. It is established that the failure of adaptive-trophic sympathetic regulation of pulmonary tissues including relevant vessels and bronchi results in diminution of pulmonary compensatory and adaptive potential. This should be allowed for in the treatment of burn disease complications.     

Dual innervation of arteries and arterioles

Summary Specific histochemical techniques for the demonstration of acetylcholinesterase and of norepinephrine have been used to study the distribution of cholinergic and adrenergic nerve fibers to arteries and arterioles in various organs of cats and dogs, including the male genital apparatus, tongue, skeletal muscle, heart and gastrointestinal tract. Arteries and arterioles in all of these organs showed both cholinergic and adrenergic nerve fibers, although the relative number of each of the types of fiber was variable. The findings provide morphologic evidence for a widespread and generalized dual adrenergic and cholinergic innervation of arteries and arterioles.Supported in part by Grant No. HE 10465 from the USPHS and by a grant from the Monroe County Heart Chapter.     

Neural connections of the heart and superior vena cava in the rabbit and man

Innervational connections of the heart and the superior vena cava wall have been studied in the rabbit and the man. Besides, series of their embryos, impregnated with silver salts after Cajal-Favorsky have been investigated. Methods of Bielschowsky-Gros, Gomori and Karnovsky-Roots have also been applied. Adrenergic nervous elements have been revealed by means of incubation the slices in 2% solution of glyoxylic acid. Abundant cholinergic and adrenergic nervous plexuses are revealed on the wall of the superior vena cava, they are tightly connected with corresponding plexuses of the heart. Developmental of these nervous connections is followed, when embryogenesis of the cardiac nervous plexuses and large major vessels is studied in serial sections of embryos and fetuses of the rabbit and the man.     

Effect of intravascular laser irradiation of blood on the status of the adrenergic and cholinergic structures of the small intestine in experimental peritonitis

In the experiment performed on 60 mongrel dogs the effect of intravascular laser radiation of blood (ILRB) to adrenergic and cholinergic fibers of the small intestine has been studied at treatment of experimental generalized suppurative peritonitis. At treatment of the experimental peritonitis by means of traditional method only one month after its termination a positive reaction to acetylcholinesterase (AChE) is noted, structural organization of cholinergic fibers corresponds to the norm, and density of their plexuses increases. Application of ILRB at treatment of the experimental peritonitis facilitates to increasing density of the cholinergic fibers already on the 21st day after termination of the treatment; their AChE increases essentially, their structural organization corresponds to the norm. In cytoplasm of neurons of the muscular-intestinal plexus a positive reaction to AChE is revealed; this demonstrates their increased functional activity. The small intestine adrenergic apparatus at peritonitis undergoes less manifested structural-chemical alterations. After termination of treatment by means of traditional methods it corresponds to the norm on the 7th day, and after ILBR treatment----on the 3d day. Thus, application of ILBR in treatment of the experimental peritonitis enhances the development of regenerative processes in adrenal and cholinergic structures of the small intestine, facilitates a more manifested demonstration of compensatory-reparative possibilities of the organism.     

Increased Activity of Choline Acetyl-transferase in Sympathetic Ganglia after Prolonged Administration of Nerve Growth Factor

A prolonged increase in the activity of preganglionic sympathetic nerves produces characteristic changes in the enzyme pattern of the postganglionic adrenergic neurones in adult rats^1–4. In newborn mice the normal development of adrenergic neurones depends materially on the intactness of the preganglionic cholinergic nerves⁵. These two findings contribute to the definition of the so far vague term “trophic response to neuronal activity” and the question arises whether these trophic actions are unidirectional only, or whether there is also a retrograde effect, that is, a dependence of the preganglionic cholinergic nerves on the function of the postjunctional adrenergic neurones. Transection experiments in the brain have shown that after lesioning of particular areas, for example, optic nerve tract, cingulate or visual cortex, there occurs not only orthograde but also retrograde trans-synaptic degeneration⁶. It seemed of interest to study this possible retrograde trophic effect in a less complex system and to investigate whether there are not only negative (degeneration) but also positive effects. The administration of nerve growth factor (NGF) to newborn rats produces a marked growth and enhanced differentiation of the adrenergic neurones⁷. The biochemical correlate to these morphological changes is a selective induction of tyrosine hydroxylase and dopamine β-hydroxylase⁸. We have investigated whether these effects are also reflected by changes in the preganglionic nerves.     

Cholinergic location of delta-opioid receptors in canine atria and SA node

Delta-opioid receptors (DORs) are associated with ischemic preconditioning and vagal transmission in the sinoatrial (SA) node and atria. Although functional studies suggested that DORs are prejunctional on parasympathetic nerve terminals, their precise location remains unconfirmed. DORs were colocalized in tissue slices and synaptosomes from the canine right atrium and SA node along with cholinergic and adrenergic markers, vesicular acetylcholine transporter (VAChT), and tyrosine hydroxylase (TH). Synapsin I immunofluorescence verified the neural character of tissue structures and isolated synaptosomes. Acetylcholine and norepinephrine measurements suggested the presence of both cholinergic and adrenergic synaptosomes. Fluorescent analysis of VAChT and TH signals indicated that >80% of the synapsin-positive synaptosomes were of cholinergic origin and <8% were adrenergic. DORs colocalized 75-85% with synapsin in tissue slices from both atria and SA node. The colocalization was equally strong (85%) for nodal synaptosomes but less so for atrial synaptosomes (57%). Colocalization between DOR and VAChT was 75-85% regardless of the source. Overlap between DOR and TH was uniformly low, ranging from 8% to 17%. Western blots with synaptosomal extracts confirmed two DOR-positive bands at molecular masses corresponding to those reported for DOR monomers and dimers. The abundance of DOR was greater in nodal synaptosomes than in atrial synaptosomes, largely attributable to a greater abundance of monomers in the SA node. The abundant nodal and atrial DORs predominantly associated with cholinergic nerve terminals support the hypothesis that prejunctional DORs regulate vagal transmission locally within the heart.     

Single dose exposure of sarin and physostigmine differentially regulates expression of choline acetyltransferase and vesicular acetylcholine transporter in rat brain

Choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) are the key components of cholinergic system apart from acetylcholinesterase. Effects of subcutaneous exposures of 0.25 and 0.5 LD(50) sarin and 0.75 mg/kg physostigmine on immunoreactivity levels of these two proteins (ChAT and VAChT) were studied. Immunoreactivity levels of ChAT decreased significantly after 1 and 3 days in cortex and 3 days of 0.25 LD(50) sarin administration in cerebellum. While 0.5 LD(50) sarin exposure caused significant down regulation after 2.5 h to 7 days in cortex and 1 and 3 days in cerebellum with respect to controls. Physostigmine at 0.75 mg/kg dose showed enhanced levels of ChAT after 1 day which decreased significantly after 3 and 7 days both in cortex and cerebellum compared to controls. VAChT level decreased significantly after 1 day in cortex and 3 and 7 days in cerebellum after 0.25 LD(50) sarin administration, while 0.5 LD(50) sarin significantly lowered VAChT immunoreactivity level after 2.5 h and 7 days in cortex and 2.5 h and 1 day in cerebellum. Physostigmine at 0.75 mg/kg dose showed significant enhanced immunoreactivity levels of VAChT after 1, 3, and 7 days in cortex and 3 days in cerebellum. Results show that acetylcholinesterase inhibition by sarin caused reduction in cholinergic neurotransmission at cholinergic proteins expression levels, while physostigmine caused differential expression of key cholinergic proteins. Moreover, cortex, which receives greater cholinergic innervations, is more susceptible to anticholinesterase effect on cholinergic gene expression. These changes can explain delayed neurocognitive changes during anticholinesterases induced chronic neurotoxicity.     

Autonomic Nervous System Regulation of Epicardial Adipose Tissue: Potential Roles for Regulator of G Protein Signaling-4

The epicardial adipose tissue (EAT) or epicardial fat is a visceral fat depot in the heart that contains intrinsic adrenergic and cholinergic nerves, through which it interacts with the cardiac sympathetic (adrenergic) and parasympathetic (cholinergic) nervous systems. These EAT nerves represent a significant source of several adipokines and other bioactive molecules, including norepinephrine, epinephrine, and free fatty acids. The production of these molecules is biologically relevant for the heart, since abnormalities in EAT secretion are implicated in the development of pathological conditions, including coronary atherosclerosis, atrial fibrillation, and heart failure. Sympathetic hyperactivity and parasympathetic (cholinergic) derangement are associated with EAT dysfunction, leading to a variety of adverse cardiac conditions, such as heart failure, diastolic dysfunction, atrial fibrillation, etc.; therefore, several studies have focused on exploring the autonomic regulation of EAT as it pertains to heart disease pathogenesis and progression. In addition, Regulator of G protein Signaling (RGS)-4 is a protein with significant regulatory roles in both adrenergic and muscarinic receptor signaling in the heart. In this review, we provide an overview of the autonomic regulation of EAT, with a specific focus on cardiac RGS4 and the potential roles this protein plays in this regulation.     

Decentralisation of neurones in the pelvic ganglion of the guinea-pig: Reinnervation by adrenergic nerves

An electron-microscopic study has been made of adrenergic and cholinergic nerve fibres and synapses in the pelvic ganglion of the guinea-pig at intervals of up to 60 days following section of the hypogastric and pelvic nerves. Transection of the hypogastric nerves led to degeneration of 80-90% of the cholinergic nerve profiles and synapses in the ganglion. The small number of adrenergic nerves and synapses did not change, but 30-60 days after section, this number increased 8-10 times. Transection of the pelvic nerves led to degeneration of about 15% of the cholinergic nerve terminals, but no change in adrenergic terminals. After transection of both hypogastric and pelvic nerves, only about 1% of cholinergic nerves survived, but after 30-60 days, the number of adrenergic nerves increased 8-10 times. It is concluded that following cholinergic nerve degeneration in the ganglion, adrenergic nerves, probably originating as collateral sprouts from postganglionic neurones and granule-containing cells, can replace them to some extent.     

Influence of cholinergic and adrenergic agents of the electric activity of the brain and the heart under hypoxia

Injection of adrenergic and cholinergic agents to animals in the normal athmospheric conditions did not tigger drastic changes on the electric activity of the brain and heart. Acutehipoxia demands high adaptability from the body. In such conditions stimulation of reticular formation and hypothalamus produces different changes in the EEG and ECG activity whith injecting adrenergic and cholinergic agents. It was determined that cholinergic influence are effective in the regulation of electrical brain activity while adrenergics are more important for the realization of descending influences of the truncus cerebri vegetative centers and are less active in the modulation of the cerebral cortex activity.     

Acute emotional stress and cyclic nucleotide content of the heart and blood plasma

The relationships between the changes in arterial pressure and the content of cyclic nucleotides in the heart and blood plasma were studied on rabbits exposed to acute emotional stress. During 3 hours of the stress program, there were changes in arterial pressure, namely an elevation within the first hour followed by a progressive fall during subsequent 2 hours and death of the animals. The content of cAMP in the heart rose to a greater degree than that of cGMP. The content of cAMP in the blood plasma considerably increased, while the level of cGMP remained unchanged. The data obtained attest to the predominance of activation of adrenergic structures over activation of cholinergic structures.     

Recent studies of the actions of cholinomimetic drugs on adrenergic nerves and their implications for the cholinergic link hypothesis

This review analyzes the results of recent studies of the actions of cholinomimetic drugs on adrenergic nerve terminals and their implications for the cholinergic link hypothesis. Thus far, evidence suggests that the only possible action of endogenous acetylcholine (ACh) present near noradrenaline (NA) stores is an inhibition of the release of NA from the adrenergic nerve terminals and that NA is released only when the action of acetylcholinesterase is inhibited. Nicotinic agents have been shown to act on adrenergic nerve terminal membranes, a finding that casts doubt on the proposed intraneuronal cholinergic sites for the action of endogenous ACh. Evidence also indicates that the mode of adrenergic neurone blocking action of bretylium and guanethidine is independent of the proposed cholinergic process in NA release. Current findings do not support the proposal that nicotinic agents in higher concentrations interfere with adrenergic neurotransmission. It is therefore concluded that nicotinic agents, in causing the release of NA from adrenergic nerve terminals, are merely exhibiting a pharmacological action and not mimicking the physiological function of ACh, as proposed by the cholinergic link hypothesis.     

Functional morphology of the neural apparatus of the hen ovary in postnatal ontogeny

When comparing the data of neurohistochemical and electron microscopic investigations in the hen and chick ovaries, adrenergic, cholinergic and, possibly, peptidergic nerve fibers have been identified. Previously described cells in the follicular internal theca are mainly SIF-cells and AChE-positive neurocytes of afferent and efferent nature. Axonal terminals make synaptic (or synaptic-like) contacts with chromaffin cells, thecocytes, pericytes of capillaries, AChE-positive motor neurons. Integral estimation, taking into account informative parameters, demonstrates that the degree of the neuromediator differentiation and age resistivity of nervous structures correlates the gland steroidogenic activity. The vascular adrenergic apparatus and chromaffin cells can be considered as potential sources of innervation and catecholamines, able to perform a compensatory function at ageing and other conditions, that are accompanied with a local deficit of sympathetic mediation.     

Cholin- and adrenergic components of the vegetative innervation of the dura mater]

Cholin- and adrenergic nerves in the fornix and base of the dura mater of rats, cats and dogs have been studied by methods of Kelle, Falck and Glenner. It has been established that the dura mater has a developed cholin- and adrenergic nervous apparatus innervating arteries, veins and the connective tissue of the mater. The concentration of nerve fibres is always greater on a meningea media and its daughter branches. The statistical processing of the data obtained has shown that the maximum quantity of nerve fibres is in cats, less in dogs and still less in rats. It has been established that in the dura fornix of cats and dogs there are more cholinergic nerve fibres than in the base. In rats there is no such difference. The amount of fibres with monoaminoxidase approximately corresponds to the amount of conductors with noradrenaline.     

Intramural ganglia of the human gallbladder: morphological and functional observations]

The purpose of this study was the reinvestigation of the intrinsic innervation of human gall bladder with an immunohistochemical technique named peroxidase anti-peroxidase (PAP). The antigen demonstrated was the S100 protein normally present in the surface of glial cells, Schwann cells and satellite cells in ganglia. The tissues used were taken from 20 human gall bladders, fixed after surgery. This technique is not specific to demonstrate adrenergic or cholinergic innervation but it reveals just myelinated fibers. The current study was undertaken in order to study the organization and the function of plexus of nerves and ganglia present in the wall of the gall bladder. The neck of the gall bladder was the region in which the higher number of nerve cells and nervous fibers was present. The technique used has demonstrated ganglionated plexus and nerves in submucosal layer, fibromuscular and adventitial layer according to the enteric nervous system. All ganglia are postganglionic stations related with preganglionic cholinergic fibers. These results confirm that the intramural ganglia of the gall bladder are analogous to those of the enteric nervous system according to their common origin.