Noradrenergic Nerve Fibers Research Articles

Immunocytochemical evidence for chromogranin A and B in neuronal elements in human gut

Chromogranins are a family of acidic proteins known to occur in the secretory granules of endocrine cells and neurons in mammals. The aim of the present study was to investigate the possible neuronal localisation of chromogranins in human intestine and their relationship with other neuronal constituents using one antibody recognizing both chromogranin A and B (CAB) and others recognizing only chromogranin A. Immunoreactive CAB was found to occur in mucosal endocrine cells and in neuronal elements of all layers throughout human gut. A few to large number of CAB-immunoreactive nerve fibers were seen in smooth muscles as well as in submucous and myenteric ganglia and they were regularly found around blood vessels. Occasional CAB immunoreactive nerve cell bodies could be demonstrated in both submucous and myenteric ganglia indicating a local origin of some of the immunoreactive fibers. Most of these neurons seemed to lack acetylcholine esterase, and could be classified as non-cholinergic. CAB coexisted with the catecholamine-synthesizing enzyme tyrosine hydroxylase indicating the presence of chromogranins in noradrenergic nerve fibers. The presence of CAB-immunoreactive nerve cell bodies indicates that some CAB-containing fibers are intrinsic in origin. The distribution of chromogranin A and B immunoreactive nerve fibers in all layers of the gut wall suggests multiple targets for neuronal CAB, and/or their processing products.

Sympathetic hyperinnervation protects vascular smooth muscle cells from necrosis in stroke-prone spontaneously hypertensive rats.

Sympathetic nerve fiber distribution and vascular smooth muscle morphology were investigated in the ophthalmic artery of stroke-prone spontaneously hypertensive rats (SHRSP) and were compared with those of normotensive Wistar Kyoto (WKY) rats at the age of 120 days. The distribution of fluorescent noradrenergic (NA) nerve fibers was examined by the glyoxylic acid method. The ophthalmic artery was divided into two portions according to the size of the outer diameter, that is into a proximal portion (above 100 microns) and a distal portion (30-70 microns). The distribution densities of noradrenergic nerve fibers were measured by quantitative image analysis using the Interactive Bild-Analyse System (IBAS). The distribution densities of NA nerve fibers in both portions of the ophthalmic artery were significantly higher (p < 0.01) in SHRSP than that in WKY rats. The difference in the density of NA fibers of the ophthalmic arteries between SHRSP and WKY rats was 1.9 times in the proximal portion and 1.5 times in the distal portion. The vascular smooth muscle cells of the ophthalmic arteries in SHRSP were observed by scanning electron microscope to examine the trophic effect of NA nerve fibers on the vascular smooth muscle cells. The smooth muscle cells of both portions of the ophthalmic arteries in SHRSP showed a smooth surface texture and no necrosis, and were very similar to those of WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Guanethidine chemical sympathectomy: spinal cord and sciatic nerve blood flow.

The spinal cord vasculature is innervated by noradrenergic nerve fibers, the role of which in the regulation of regional spinal cord blood flow (RSCBF) is presently unclear. We used the distribution of [14C]butanol to simultaneously measure RSCBF at seven cord levels and the regional blood flow in sciatic nerve (NBF), truncal skin, and biceps femoris muscle. The subjects were control rats and rats that had been given parenteral guanethidine sulfate for 5 wk to induce selective postganglionic "chemical sympathectomy." Flows were measured under basal conditions (group I) and immediately after an arterial hemorrhage (group II). The results indicate that RSCBF was unchanged from control after guanethidine administration in both groups; however, NBF was elevated after guanethidine by 47% in group I and by 41% in group II. We conclude that in the spinal cord as in the brain, sympathetic inflow does not appear to have an important role in the regulation of regional blood flow. Sympathetic inflow appears to partly regulate NBF, however, probably by varying vascular tone.

Splenic Norepinephrine Is Decreased in MRL- lpr/ lpr Mice

The MRL-lpr/lpr mouse, a genetic model of the human autoimmune disease systemic lupus erythematosus, has been studied extensively to determine the etiology and the pathological course of the disease in lymphoid organs. At approximately 8 weeks of age, splenomegaly develops due to a massive increase in an abnormal population of T cells, resulting in a disruption of the normal splenic architecture. Part of the normal splenic architecture includes postganglionic noradrenergic sympathetic nerve fibers, which can exert influence on a variety of immunological functions. Noradrenergic innervation and norepinephrine content of spleens from both male and female MRL-lpr/lpr mice and MRL-+/+ congenic controls were examined at 6, 12, 18, and 24 weeks of age. Norepinephrine content is reduced in MRL-lpr/lpr male and female mice prior to the onset of observed splenomegaly and remains reduced at all ages examined. Remaining noradrenergic fibers are found in their usual compartments, but are greatly diminished compared with controls.

Noradrenergic and acetylcholinesterase-positive nerve fibres of the uterus in sexually immature and cycling rats.

The distribution and density of the noradrenergic and acetylcholinesterase-positive nerve fibres were histochemically studied in different uterine regions of prepubertal and cycling rats in dioestrus and oestrus. Besides the rich and double innervation of blood vessels, both types of nerve fibre were found in the myometrium and cervical musculature. The non-vascular noradrenergic network looked denser at the tubal end of the horns and at the cervix, whereas the acetylcholinesterase-positive innervation was poor at the tubal end, increasing toward the cervix. Contrasting with the middle third of the uterine horn, at the tubal end, the myometrial longitudinal layer was much more innervated than the circular one, especially by the noradrenergic nerve fibres. The prepubertal rats presented an adult pattern of uterine autonomic innervation. In the cycling animals, this innervation was nearly the same during oestrus and dioestrus regarding both the density of nerve fibres and intensity of the histochemical reactions.

Innervation of the human adrenal cortex: simultaneous visualisation using acetylcholinesterase histochemistry and dopamine beta-hydroxylase immunohistochemistry.

The inter-relationship between putative cholinergic and noradrenergic innervation of the human adrenal cortex was investigated using a technique which combined acetylcholinesterase histochemistry, choline acetyltransferase radiochemistry and dopamine beta-hydroxylase immunohistochemistry. Cholinergic and noradrenergic nerve fibres had a near-identical distribution, with varicose noradrenergic fibres located immediately alongside non-varicose cholinergic nerve bundles in all cortical zones. Choline acetyltransferase activity was consistently detected in the adrenal cortex, confirming the presence of cholinergic neurons. It is postulated that noradrenergic innervation has a role in the modulation of cortical endocrine secretion, while cholinergic nerves are mainly concerned with the control of medullary secretion.

Fundamental Aspects of Neural-Immune Signaling

Noradrenergic and peptidergic nerve fibers abundantly innervate the parenchyma of both primary (bone marrow) and secondary (spleen, lymph nodes) lymphoid organs. Nerve fibers distribute within the parenchyma of these organs, as well as along smooth muscle compartments. Both noradrenaline and peptides such as substance P have been shown to fulfill the basic criteria for neurotransmission with lymphocytes, macrophages, and other immunocytes as targets. Denervation or pharmacological manipulation of these neurotransmitters can profoundly alter immunological reactivity at the individual cellular level, at the level of complex multicellular interactions (such as antibody response), and at the level of host response to a disease-producing challenge. The characteristic and mechanisms of bidirectional neural-immune signaling may provide a novel approach to immunologically-mediated disease, both pharmacologically and behaviorally.

Direct innervation of lymphoid organs: substrate for neurotransmitter signaling of cells of the immune system.

The nervous system can generate outflow capable of signaling cells of the immune system via two routes: (1) hormonal influences via hypothalamopituitary-target organ activation, and (2) neurotransmitter influences via direct innervation of the parenchyma of both primary and secondary lymphoid organs. Both noradrenergic and neuropeptidergic nerve fibers are found directly adjacent to cells of the immune system in bone marrow, thymus, spleen, lymph nodes, and other sites. These neurotransmitters can modulate immune responsiveness at several levels, including individual cellular functions, collective cellular interactions and immune responses, and overall host immunological response to a challenge by bacteria, viruses, tumor cells, or other sources. The ability of neural signals to modulate immune responsiveness is influenced by such factors as co-localization with other neurotransmitters, synergistic or dual signaling by neurotransmitters and cytokines, hormonal influences on ligand availability or receptor responsiveness, extent of catabolism and inactivation of the neural signal, and unique chemical and morphological aspects of the specific compartmentation of the lymphoid organ in which signaling is taking place. Thus, neural-immune signaling is a complex and dynamic process, with bidirectional interactions in a complex microenvironment.

Regeneration of Sympathetic Activities in Small Bowel Transplants

In order to study the activity of noradrenergic nerve fibres along mesenteric arteries in small-intestinal grafts, the entire jejunoileum was transplanted heterotopically in an isogeneic rat model (group I, n = 12). To assess their influence on graft motility, 9 cm of jejunum were transplanted in an orthotopic position and three bipolar electrodes sutured to the seromuscular layer of the graft (group II, n = 10). Fasting motility was recorded up to postoperative day 42. Animals of group I were sacrificed from day 7 on at weekly intervals and mesenteries were analysed histochemically by fluorescence microscopy. After the 1st and 2nd week, grafts were found to be completely depleted of noradrenaline. At the end of the 3rd week, fluorescence became detectable along graft mesenteric arteries and showed normal intensity from the end of week 4. Migrating myoelectric complexes (MMCs) were present in all animals of group II. The variability of the MMC period (mean 12.6 min; SD 6.2 min) expressed as variation coefficient (median 36.5; 14.6-74) did not change during the observation period. From these findings it is concluded that there are no extrinsic noradrenergic activities in rat small-intestinal transplants for the first 3 postoperative weeks but they do recover there after. Their influence on graft function remains unclear: MMC periodicity, however, was no influenced.

Extrinsic control of the release of galanin and VIP from intrinsic nerves of isolated, perfused, porcine ileum

By immunohistochemistry galanin-like immunoreactivity and vasoactive intestinal polypeptide (VIP)-like immunoreactivity were found in nerve cell bodies mostly in the submucous plexus and in nerve fibres in the mucosa, submucosa and muscularis including the myenteric plexus of the porcine ileum and were found to co-exist in most of these structures. Using isolated, perfused porcine ileum we studied the release of galanin and VIP in response to electrical stimulation of the mixed periarterial nerves or to intraarterial infusions of different neuroactive agents. Nerve stimulation (4–10 Hz) inhibited the basal release of galanin and VIP from the ileum (to 69 ± 6 and 62 ± 6% of basal release). After infusion of the α-adrenergic blocker, phentolamine, (10 −6 M) electrical stimulation increased the release of both galanin and VIP (to 140 ± 12 and 133 ± 13% of basal output). This increase was abolished by atropine (10 −6 M) and by hexamethonium (3·10 −5 M). Infusion of norepinephrine (10 −6 M) inhibited, whereas acetylcholine (10 −6 M) stimulated the release of both peptides. The effect of the latter was abolished by atropine. The inhibitory effect of nerve stimulation was not influenced by atropine. Our results suggest that the galanin- and VIP-producing intrinsic neurons receive inhibitory signals by noradrenergic nerve fibers and stimulatory signals mediated by cholinergic nerves, possibly via a cholinergic interneuron.

Noradrenergic nerve fibers of the rectal mucosa in autonomic disorders: comparison of histochemical study with clinical severity and changes in plasma noradrenaline induced by standing

A histochemical study was carried out on the rectal mucosae biopsied from 20 patients with autonomic dysfunctions and 13 controls using a catecholamine fluorescent staining method, and the rectal noradrenergic nerve fiber lesions were compared with the severity of autonomic symptoms and disturbance of plasma noradrenaline increase in response to standing in 17 patients. In 9 patients with type I familial amyloid polyneuropathy and 1 with acute pandysautonomia, the number of fluorescent nerve fibers was greatly reduced, and the degree of depletion correlated well with the other 2 parameters showing the severity of autonomic dysfunction. In contrast, rectal noradrenergic nerve fibers were normally preserved in 10 patients with multiple system atrophy, although they suffered from severe autonomic symptoms with poor noradrenaline response to the postural loading. It is concluded that noradrenergic nerve fiber lesions in the biopsied rectal mucosa may represent the systemic involvement of sympathetic post-ganglionic nerves.

Lymphocyte-mediated regulation of neurotransmitter gene expression in rat sympathetic ganglia

It has been previously shown that sympathetic noradrenergic nerve fibers, in addition to supplying the smooth muscle of the splenic capsule, trabeculae and blood vessels, also form very tight appositions with lymphocytes of the periarteriolar lymphatic sheath. To determine whether there is a direct communication between the sympathetic neurons and the immune cells we have grown dissociated superior cervical ganglion (SCG) neurons together with splenic lymphocytes. Sympathetic neurons were grown both as mixed preparations (neurons and non-neuronal ganglion cells) and neuron-enriched preparations. These systems were used to investigate whether coculture with splenocytes alters neurotransmitter gene expression in SCG cultures. Northern blot analysis was used to measure changes in neurotransmitter mRNA expression. The results showed that expression of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, was significantly decreased when SCG cultures were grown in the presence of spleen cells compared to control SCGs grown either alone or in the presence of erythrocytes. When the mitogen concanavalin A (ConA) was used to stimulate the spleen cells in the cocultures the decrease in TH was more pronounced. In contrast, preprochykinin-A (PPT-A) mRNA expression in cultured SCGs increased in the cocultures. Another neuropeptide, neuropeptide Y (NPY), showed different responses in the, presence of stimulated vs. unstimulated splenocytes. NPY mRNA was slightly increased in the presence of resting spleen cells, but showed a 70% decreased when ConA was added to the Thus, our results suggest that lymphocytes can differentially regulate neurotransmitter gene expression in sympathetic ganglia.

Neuropeptide-Y innervation of the rat spleen: Another potential immunomodulatory neuropeptide

Neuropeptide-Y (NPY) is a 36 amino acid peptide that acts as a chemical messenger in the central and peripheral nervous systems. NPY often is found colocalized with the classical neurotransmitter norepinephrine (NE) and can potentiate the effects of this neurotransmitter postsynaptically in many systems. Using immunocytochemistry for NPY and specific lymphoid cell markers, we mapped the distribution of NPY-positive nerve fibers in the rat spleen. NPY-positive nerve fibers were present along the vasculature, trabeculae, and capsule, and also were found associated with specific lymphoid parenchymal compartments of the spleen, in close contact with lymphocytes and macrophages. These contacts were investigated further at the electron microscopic level. NPY-positive nerve terminals were found in close apposition with lymphocytes in the periarteriolar lymphatic sheath, and with lymphocytes and macrophages in the marginal zone. Previous studies have reported that postganglionic noradrenergic nerve fibers innervate specific lymphoid compartments of the rat spleen, with nerve terminals forming direct appositions with cells of the immune system. The possible colocalization of NPY and NE in these nerve fibers was investigated by chemical sympathectomy with 6-hydroxydopamine, followed by immunocytochemical labeling of NPY and tyrosine hydroxylase (TH), the rate-limiting enzyme in norepinephrine synthesis. Colocalization also was investigated by labeling for NPY with a fluorescent label, eluting the NPY, and staining for TH with diaminobenzidine as the label. These studies demonstrate that norepinephrine and NPY are colocalized in the postganglionic sympathetic nerve fibers of the rat spleen. Further studies are needed to determine whether lymphocytes and macrophages possess receptors for NPY, whether NPY fulfills the criteria for neurotransmission, and whether NPY plays a role in immunological phenomena either directly or by modulating norepinephrine.

Immunohistochemical Distribution of Neuropeptide Y and Catecholamine-Synthesizing Enzymes in Nerve Fibers of the Human Liver

The course and distribution of neuropeptide Y (NPY)-immunoreactive (ir) nerves in the human liver was studied using immunohistochemistry. The distribution and density of NPY-ir fibers was compared with tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) immunoreactivity, two enzymes which are markers for dopamine- and noradrenaline-synthetizing neurones. NPY-immunopositive nerve fibers were densely distributed in the perivascular plexus of the portal trials, along the vena centralis, as well as close to the sinusoids and hepatocytes. The distribution of perivascular TH-ir and DBH-ir nerve fibers was similar to that of NPY-ir nerves, with the exception of intralobular nerves, where close topographical relations to individual hepatocytes and sinusoids were rarely observed. These results suggest that NPY is present in noradrenergic perivascular nerve fibers; probably of sympathetic origin and also in other parasympathetic, presumably cholinergic nerve fibers around the sinusoids.

μ-opioid receptor-mediated inhibition of the release of radiolabelled noradrenaline and acetylcholine from rat amygdala slices

Abstract Presynaptic modulation by opioids of electrically-evoked neurotransmitter release from superfused rat amygdala slices prelabelled with [ 3 H]noradrenaline (NA) and [ 14 C]choline was examined. Both [ 3 H]NA and [ 14 C]acetylcholine release were strongly inhibited by morphine, the mixed δ / μ -receptor agonist [ d -Ala 2 , d -Leu 5 ]enkephalin (DADLE) and the highly selective μ-agonist [ d -Ala 2 , MePhe 4 , Gly-ol 5 ]enkephalin (DAMGO), whereas the highly selective δ-agonist [ d -Pen 2 , d -Pen 5 ]enkephalin and the κ-agonist bremazocine were without effect. The inhibitory effects were potently antagonized by naloxone but not by the selective δ-receptor antagonist fentanylisothiocyanate. When the selective uptake inhibitor desipramine was used to prevent uptake of [ 3 H]NA into noradrenergic nerve terminals, but sparing the uptake into dopaminergic nerve terminals, the electrically evoked release of tritium was strongly inhibited by bremazocine but not by DADLE or DAMGO. The data indicate, that in the amygdala transmitter release from dopaminergic nerve fibres is inhibited only via activation of κ-receptors, whereas transmitter release from noradrenergic and cholinergic nerve fibers is subjected to inhibition by opioids via activation of μ-receptors only. Regional differences and similarities of modulation of neurotransmitter release by opioids in the rat brain are briefly discussed.

A presynaptic excitatory M1 muscarine receptor at postganglionic cardiac noradrenergic nerve fibres that is activated by endogenous acetylcholine

Rabbit atria were isolated with the extrinsic right vagus and sympathetic nerves intact and perfused with Tyrode solution. Noradrenaline overflow evoked by sympathetic nerve stimulation (SNS) at 3 Hz for 3 min was determined before, during, and after vagus nerve stimulation (VNS), also at 3 Hz and for 3 min. The VNS pulses preceded the SNS pulses by 3, 100 and 233 ms. Acetylcholine overflow was determined after labelling of the transmitter stores with [14C]choline. Pirenzepine 80 nmol/l failed to alter the muscarinic inhibition of noradrenaline overflow when the vago-sympathetic impulse intervals were 3 and 233 ms. At an interval of 100 ms VNS did not significantly inhibit noradrenaline overflow in the absence of pirenzepine but produced an inhibition in the presence of the drug. When the pirenzepine concentration was varied (0.4-300 nmol/l) the largest inhibition of noradrenaline overflow was observed at 5.7 nmol/l whereas 300 nmol/l fully antagonized the inhibition. Acetylcholine overflow evoked by VNS was not altered by pirenzepine 0.4-300 nmol/l. AF-DX 116 (11-[(2[(diethylamino)methyl]-1-piperidinyl)-acetyl]-5, 11-dihydro-6H-pyrido-[2,3-b]-[1,4]benzodiazepine-6-one), an M2 receptor selective antagonist, concentration-dependently (100-800 nmol/l) inhibited the decrease of tension development elicited by VNS. At the 100 ms vago-sympathetic impulse interval noradrenaline overflow was enhanced in the presence of AF-DX 116 400 and 800 nmol/l. However, already 100 nmol/l of the drug caused a maximum (fourfold) increase of acetylcholine overflow. It is concluded that acetylcholine released onto noradrenergic nerve fibres causes a small facilitation of noradrenaline overflow at a vago-sympathetic impulse interval of 100 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Noradrenergic reinnervation of the rat spleen following chemical sympathectomy with 6-hydroxydopamine: Pattern and time course of reinnervation

The time course and pattern of reinnervation of noradrenergic (NA) sympathetic nerve fibers into the spleen following acute chemical sympathectomy with the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) was examined in young adult male Fischer 344 rats using glyoxylic acid fluorescence histochemistry and neurochemical measurement of NE. Reinnervation proceeds initially along the splenic artery as it enters the hilus (1–5 days), extends into the hilar region (5–10 days), and later proceeds into the regions distal to the hilus (21–56 days), suggestive of orderly growth from the hilar region to distal regions. In all 6-OHDA-treated spleens, the compartmentation of NA innervation was similar to that observed in saline-injected controls, but the density of NA nerve fibers in these compartments differed according to the distance from the hilus. By 56 days postlesion, regions distal to the hilar blood vessels contained fewer NA profiles than their age-matched controls, suggesting that the anatomical process of reinnervation does not restore the density of fibers in a fashion identical to that of nondenervated controls. In contrast, splenic NE concentration at 56 days postdenervation did not differ from the concentration seen in nondenervated control spleens. We suggest that functional restoration of splenic innervation may involve metabolic and receptor compensation for the lack of complete fiber regrowth into regions of white pulp distal from the hilus.

Some parasympathetic neurons in the guinea-pig heart express aspects of the catecholaminergic phenotype in vivo

In a histochemical study of intrinsic cardiac ganglia of the guinea-pig in whole-mount preparations, it was found that some 70-80% of the neurons express aspects of the catecholaminergic phenotype. These neurons have an uptake mechanism for L-DOPA, and contain the enzymes for converting L-DOPA (but not D-DOPA) to dopamine and noradrenaline, i.e. aromatic L-aminoacid decarboxylase and dopamine beta-hydroxylase. Monoamine oxidase is also present within some of the neurons. In these respects, the neurons resemble noradrenergic neurons of sympathetic ganglia, so we refer to them as intrinsic cardiac amine-handling neurons. However, these neurons do not contain tyrosine hydroxylase and show little or no histochemically detectable uptake of alpha-methyldopa, dopamine or noradrenaline, even after depletion of endogenous stores of amines by pre-treatment with reserpine. Noradrenergic fibres from the sympathetic chain form pericellular baskets around nerve cell bodies. The uptake of L-DOPA into nerve cell bodies is not prevented by treatment with 6-hydroxydopamine sufficient to cause transmitter-depletion or degeneration of the extrinsic noradrenergic fibres. Such degeneration experiments suggest that axons of the amine-handling neurons project to cardiac muscle, blood vessels and other intrinsic neurons. The cardiac neurons do not show any immunohistochemically detectable serotonergic characteristics; there is no evidence for uptake of the precursors L-tryptophan and 5-hydroxytryptophan or 5-HT itself, whereas the extrinsic noradrenergic nerve fibres within the ganglia can take up 5-HT when it is applied in high concentrations.

Innervation of lower airways and neuropeptide effects on bronchial and vascular tone in the pig

The occurrence and distribution of peptide-containing nerve fibres [substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY)] and noradrenergic nerve fibres [tyrosine hydroxylase (TH)- and dopamine beta hydroxylase (DBH)-positive] in the airways of the pig were studied by means of immunohistochemistry. SP- and CGRP-immunoreactive (-IR) nerve fibres were present close to and within the lining respiratory epithelium, around blood vessels, within the tracheobronchial smooth muscle layer and around local tracheobronchial ganglion cells. The content of CGRP- and neurokinin A (NKA)-like immunoreactivity (-LI) measured by radioimmunoassay (RIA) was twice as high in the trachea compared to that in the peripheral bronchi. SP was a more potent constrictor agent than NKA on pig bronchi in vitro. CGRP had a relaxant effect on precontracted pig bronchi. On blood vessels CGRP exerted a relaxant effect that was more pronounced on pulmonary arteries than on bronchial arteries. VIP/PHI-IR fibres were seen in association with exocrine glands and in the tracheobronchial smooth muscle layer. VIP-positive nerve fibres were abundant around blood vessels in the trachea but sparse or absent around blood vessels in the peripheral bronchi. This histological finding was supported by RIA; it was shown that the content of peptides displaying VIP-like immunoreactivity (-LI) was 18 times higher in the trachea compared to peripheral bronchi. VIP was equally potent as CGRP in relaxing precontracted pig bronchi in vitro. Both bronchial and pulmonary arteries were relaxed by VIP. NPY was colocalized with VIP in tracheal periglandular nerve fibres and in nerve fibres within the tracheobronchial smooth muscle layer. NPY was also present in noradrenergic (DBH-positive) vascular nerve fibres. The content of NPY was much higher (15-fold) in the trachea compared to small bronchi. NPY caused a contraction of both pulmonary and bronchial arteries. The bronchial smooth muscle contraction to field stimulation in vitro was purely cholinergic. A noncholinergic relaxatory effect following field stimulation was observed after bronchial precontraction. Capsaicin had no effect on pig bronchi in vitro.

The noradrenergic innervation of the ovary in old rats

The influence of ageing on the noradrenergic innervation of the ovary was studied in female Wistar rats using high pressure liquid chromatography (HPLC) with electrochemical detection and catecholamine histofluorescence techniques. Old age was accompanied by a significant decrease in ovarian noradrenaline levels. In young animals (3-month-old) noradrenergic nerve fibres were distributed primarily to blood vessels and in lesser amounts to the interstitial glands. In aged animals (24-month-old) perivascular noradrenergic fibres were reduced by more than 40%; interstitial gland nerve fibres were reduced by approximately 20%. The possibility that impaired noradrenergic ovarian innervation occurring in old age may be in some way related with age-dependent failure in reproductive activity is discussed.