Biomedical subjects

J Lincoln

Publications and source records attributed to J Lincoln.

At least 55 records · Page 3Linked to original sources

PubMed1989

Adenosine 5'-triphosphate, adenosine and endothelium-derived relaxing factor in hypoxic vasodilatation of the heart.

The involvement of ATP in hypoxic vasodilatation was investigated using isolated perfused guinea-pig hearts (Langendorff). Reactive blue 2, a selective P2Y-purinoceptor antagonist, attenuated dilatations due to ATP and hypoxia. Hydroquinone, an agent which destroys endothelium-derived relaxing factor, substantially decreased dilatations due to 2-methylthioATP, a potent P2Y-purinoceptor agonist, and hypoxia, but not to adenosine. ATP may, therefore, have an important role to play in the initiation of hypoxic dilatation which is mediated by the release of endothelium-derived relaxing factor.

Adenosine↗

PubMed1989

Ultrastructural localisation of substance P and choline acetyltransferase in endothelial cells of rat coronary artery and release of substance P and acetylcholine during hypoxia.

Substance P and choline acetyltransferase have been localised in a small proportion of endothelial cells of rat coronary arteries using electron microscopic immunocytochemistry. During a hypoxic period of 1 min, coronary vasodilatation was produced in the Langendorff heart preparation and increased levels of substance P and acetylcholine were released into the perfusate. The possibility that these substances are released from endothelial cells during hypoxia and contribute to the hyperaemic response is discussed.

Acetylcholine↗

PubMed1989

Alterations in serotonin and neuropeptide Y content of cerebrovascular sympathetic nerves following experimental subarachnoid hemorrhage.

The effect of an experimental subarachnoid hemorrhage (SAH) upon neurotransmitter content in sympathetic nerves supplying the major cerebral arteries of the rat has been examined by immunohistochemical analysis and high performance liquid chromatography with electrochemical detection (HPLC-ECD). In particular, changes that occur in sympathetic nerve content of the vasoconstrictor agents serotonin (5-HT) and neuropeptide Y (NPY), which are colocalized with noradrenaline, were assessed. Subarachnoid hemorrhage was induced by a single injection of autologous arterial blood into the cerebrospinal fluid (CSF) space of the cisterna magna. The density of 5-HT-containing and NPY-containing perivascular nerve fibers per unit area of vessels was measured at defined intervals from 15 min to 5 days post-SAH. In addition, an HPLC study was performed to quantify the actual amounts of 5-HT and noradrenaline present in circle of Willis vessels at 3 h post-SAH. Comparison was made with sham-operated animals and animals that received a cisternal injection of buffered saline in place of blood. Our results reveal a major increase in cerebrovascular sympathetic nerve content of serotonin, arising by uptake, presumably from subarachnoid blood clot, within the first 3 h post-SAH. Neuropeptide Y content, however, decreased from 3 up to 48 h posthemorrhage. By 3 days post-SAH, when the majority of subarachnoid clot had resorbed, the sympathetic nerve content of both NPY and 5-HT was restored to normal. This pattern of change was not observed in either sham-operated or saline-injected controls.

Animals↗

PubMed1989

The hypothalamo-neurohypophysial system in streptozotocin-diabetic rats. Ultrastructural evidence for neuronal alterations in the supraoptic and paraventricular nuclei and in the neurohypophysis.

The ultrastructure of the hypothalamo-neurohypophysial system of rats was examined 8 weeks after streptozotocin-induction of type I diabetes. These studies provided evidence for numerous neuronal alterations to the hypothalamo-neurohypophysial system in streptozotocin-diabetic rats. Changes were observed in the somata, dendrites and axons of both the supraoptic and paraventricular nuclei as well as in axon profiles in the neurohypophysis. Many of these changes suggest an increased activity of the hypothalamo-neurohypophysial complex, with increased synthesis of neurohypophysial hormones in the hypothalamus together with depletion of neurosecretory granules in axons in the neurohypophysis. Some degenerative changes, however, were also observed. It is proposed that chronic dehydration and hypoxia in diabetes may contribute to the ultrastructural reorganization of the hypothalamo-neurohypophysial complex in streptozotocin-diabetic rats.

Animals↗

PubMed1988

Serotonin is localized in endothelial cells of coronary arteries and released during hypoxia: a possible new mechanism for hypoxia-induced vasodilatation of the rat heart.

In this report we demonstrate the immunocytochemical localization of serotonin in endothelial cells of rat coronary vessels and a significant increase in the release of serotonin into the perfusate of Langendorff rat heart preparations during hypoxia. It is suggested that serotonin, localized in endothelial cells, is released during hypoxia and could provide part of a pathophysiological mechanism for vasodilatation to protect the heart from damage due to hypoxia.

Animals↗

PubMed1988

NMDA receptor activation and early olfactory learning.

Norway rat pups have an enhanced olfactory bulb response to odors which they have learned to prefer early in life. When N-methyl-D-aspartate receptors are blocked pharmacologically before olfactory preference training, both the behavioral preference and the enhanced olfactory bulb response to the learned odor are suppressed. These results implicate the activation of these receptors in the kind of neural and behavioral plasticity that normally occurs during development.

2-Amino-5-phosphonovalerate↗

PubMed1988

Increased density of perivascular nerves to the major cerebral vessels of the spontaneously hypertensive rat: differential changes in noradrenaline and neuropeptide Y during development.

Fluorescence and immunohistochemical techniques were used to study the pattern and density of perivascular nerves containing noradrenaline (NA) and neuropeptide Y (NPY) supplying the major cerebral arteries of 4-, 6-, 8- and 12-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar (WIS) controls. Levels of NA and NPY in the superior cervical ganglia were measured. The density of nerves containing NA and NPY was greater in the hypertensive animals at all ages studied. However, the developmental changes in the density of innervation showed similar trends in both SHR and WIS groups. With few exceptions, there was a significant increase in the density of nerves containing NA from 4 to 6 weeks and from 8 to 12 weeks of age. This was in contrast to a low expression, and in some vessels a significant decrease in the number of NPY-containing nerves from 4 to 6 weeks. The density of nerve fibres containing NPY increased significantly in almost all vessels between 6 and 8 weeks of age and then stabilized. Thus there is a differential time course for the appearance of NA and NPY during development. Furthermore, the hyperinnervation of cerebral vessels in SHR by nerves containing NA and NPY precedes the onset of hypertension and associated medial hypertrophy. High-performance liquid chromatography and enzyme-linked immunosorbant assays show that the NA and NPY contents of the superior cervical ganglion do not reflect the changes in innervation pattern seen in the terminal fibres in the cerebral arteries. This tends to support the view that a local neurovascular mechanism is involved in the maintenance of hypertension. The possibility that increase in NPY as well as NA in cerebral perivascular nerves of hypertensive animals is involved in the protection of the blood-brain barrier against oedema and cerebral haemorrhage is raised.

Aging↗

PubMed1988

The hypothalamo-neurohypophysial system in streptozotocin-diabetic rats: ultrastructural and immunocytochemical evidence for alterations of oxytocin- and vasopressin-containing neuronal profiles.

The hypothalamic paraventricular and supraoptic nuclei and the neurohypophysis of rats were investigated 8 weeks after streptozotocin (STZ)-induction of type 1 diabetes. Vasopressin (VP)- and oxytocin (OT)-containing neuronal profiles were examined using the pre-embedding peroxidase-antiperoxidase technique for electron microscopy. Ultrastructural alterations were observed in the somata, dendrites and axons of VP- and OT-labelled profiles. There was no evidence, however, for alterations in the synapses associated with VP- or OT-labelled somata, dendrites and axons. The results indicate that both VP- and OT-containing neuronal profiles are involved in the ultrastructural reorganisation of the hypothalamo-neurohypophysial complex during diabetic conditions. Depletion of VP- and OT-containing axon profiles in the neurohypophysis may suggest increased release of both neurohypophysial hormones in STZ-induced diabetes.

Animals↗

PubMed1988

Progressive changes in adrenergic, serotonergic, and peptidergic nerves in proximal colon of streptozotocin-diabetic rats.

The effect of progression of diabetes on adrenergic, serotonergic, and peptidergic innervation of the proximal colon of the rat at 8, 16, and 25 wk after induction of diabetes with streptozotocin was investigated using immunohistochemical, biochemical, and immunochemical methods. Two different responses to diabetes emerged from the present study. The first response, which involves noradrenaline and vasoactive intestinal peptide, was characterized by a sign of degeneration, where there was an initial increase in tissue level and immunoreactivity of the transmitters followed by a decrease in tissue level and density of nerve fibers at 16 and 25 wk after induction of diabetes. The second response, which involves 5-hydroxytryptamine, substance P, and calcitonin gene-related peptide, was characterized by changes in tissue level and immunoreactivity of the transmitters with no evidence of degeneration. The third feature was one of resistance to change due to diabetes, which was demonstrated by neuropeptide Y-containing nerves, where there was neither a change in tissue level of neuropeptide Y nor a change in immunoreactivity. It seems likely that the overall changes described will have profound implications in the function of the gut in the streptozotocin-diabetic rat model that may have some parallels in diabetic humans.

Animals↗

PubMed1988

Adrenergic, but not cholinergic or purinergic, responses are potentiated in the cecum of diabetic rats.

Electrophysiologic properties of smooth muscle strips from the circular muscle of the cecum were compared in streptozocin-treated diabetic (8 wk) and untreated control rats using the sucrose-gap technique. Changes in membrane potential elicited by field stimulation (0.03-32 Hz) and by exogenously applied adenosine triphosphate (10-1000 microM) and noradrenaline (0.03-10 microM) were measured. Nonadrenergic, noncholinergic inhibitory junction potentials were the predominant response to field stimulation. However, in some preparations from both diabetic and control tissues, the inhibitory junction potential was preceded by a small nonadrenergic, noncholinergic excitatory junction potential. In nonatropinized preparations, a cholinergic excitatory junction potential was occasionally elicited; there was no difference between these cholinergic responses in diabetic and control tissues. The inhibitory junction potentials and the hyperpolarization in response to adenosine triphosphate were similar in diabetic and control tissues, although the rate of hyperpolarization of the single inhibitory junction potential was slower in the diabetic tissues. In contrast, exogenous application of noradrenaline revealed significantly greater hyperpolarizing responses in diabetic compared with control tissues. This increase in potency appeared to be due, in part, to an increased sensitivity of alpha-adrenoceptors on smooth muscle. There was no evidence for beta-adrenoceptor activation by noradrenaline. Prejunctional inhibition of the nonadrenergic, noncholinergic neuromuscular transmission by noradrenaline was not affected by streptozocin-induced diabetes. The induced changes in adrenoceptor activity were selective for the postjunctional alpha-adrenoceptors.

Acetylcholine↗

PubMed1988

Increase in neuropeptide Y, but not noradrenaline, in the superior cervical ganglion of rabbits chronically exposed to cold.

We have investigated the effects of exposure to cold for 8 days on sympathetic neurones supplying the ear artery of the rabbit using a combination of assay and quantitative morphological techniques. The concentration of neuropeptide Y was shown to be significantly higher in the superior cervical ganglion of cold-exposed animals. Although the noradrenaline and dopamine levels in the ganglion were not significantly changed, the ratio of noradrenaline to dopamine was significantly increased after exposure to cold. The density of noradrenergic nerves supplying the ear artery was found to be unaffected by cold exposure. Since noradrenaline and neuropeptide Y have been shown to coexist in the majority of neurones of the superior cervical ganglion, the present study appears to provide an example of differential control of expression of neurotransmitters contained within the same neurone.

Animals↗

PubMed1987

Lack of release of vasoactive intestinal polypeptide and calcitonin gene-related peptide during electrical stimulation of enteric nerves in streptozotocin-diabetic rats.

The simultaneous release of endogenous acetylcholine, serotonin, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide was measured during electrical field stimulation of isolated preparations of rat ileum from control and 8-wk streptozotocin-treated diabetic rats. Electrical field stimulation of the control rat ileum caused a significant increase in the release of all the above substances from the enteric nerves. The electrically evoked, but not the basal, release of these substances was inhibited by tetrodotoxin. In the diabetic rat ileum, however, there was no increase in the release of vasoactive intestinal polypeptide and calcitonin gene-related peptide during electrical stimulation, whereas endogenous release of acetylcholine, serotonin, and substance P was unaffected by the diabetic state. This was surprising in view of the increased fluorescence intensity and tissue content of vasoactive intestinal polypeptide-like immunoreactivity in the same tissue reported previously. The lack of increase in evoked release of vasoactive intestinal polypeptide in the diabetic preparations might be due to an impaired mechanism of release at the terminal site or to defective axonal transport of the peptide, whereas in the case of calcitonin gene-related peptide, it might be the result of the low level of the peptide present in the enteric nerve fibers of the diabetic rat ileum. The differential effect of diabetes on enteric nerves is discussed.

Acetylcholine↗

PubMed1987

Histochemical and biochemical investigation of adrenergic, cholinergic and peptidergic innervation of the rat ventral prostate 8 weeks after streptozotocin-induced diabetes.

The gross anatomy and autonomic innervation of the ventral prostate glands was examined in control and streptozotocin-induced diabetic rats. The most striking finding was the consistent reduction in size and the gross atrophy of the prostates from diabetic rats. No change was detected in the total content of noradrenaline in the alveolar lobes or in the levels of vasoactive intestinal polypeptide, neuropeptide Y and substance P in the whole prostates of diabetic rats. However, histochemical and immunohistochemical investigations revealed localized reductions in density and/or fluorescence intensity of noradrenaline-containing nerve fibres and increased density and/or fluorescence intensity of vasoactive intestinal polypeptide- and neuropeptide Y-containing nerve fibres in the alveolar smooth muscle of a majority of diabetic animals. No changes in acetylcholinesterase-staining nerve fibres were seen. The adrenergic component of the autonomic nervous system in this gland appears to be particularly susceptible to change in diabetes.

Adrenergic Fibers↗

PubMed1987

A study of bladder dysfunction during streptozotocin-induced diabetes in the rat using an in vitro whole bladder preparation.

An in vitro whole bladder preparation has been used in this study to examine the effects of eight and 16 week streptozotocin-induced diabetes on detrusor function in the rat. In eight week animals cystometric recordings showed an increase in bladder capacity associated with a decrease in intraluminal pressure. Concentration-response curves revealed a significant increase in sensitivity of the detrusor to beta,gamma-methylene ATP, a potent purinergic agonist, and a trend towards subsensitivity to acetylcholine in bladders from eight week diabetic rats when compared to controls. The atropine-resistant (purinergic) response to neurogenic stimulation was increased over the frequency range two to 30 Hz and was significantly greater at two Hz. In 16 week animals the cystometrogram had partially recovered; capacity had decreased compared to eight week diabetics and intraluminal pressure was within the normal range. Concentration-response curves revealed no significant difference in the response to acetylcholine and a greatly reduced response to beta,gamma-methylene ATP in the 16 week diabetics compared to controls. The atropine-resistant neurogenic response was slightly, but not significantly reduced. The results are discussed in relation to clinical urodynamic measurements of human detrusor dysfunction in diabetes.

Acetylcholine↗

PubMed1987

Changes in the VIPergic, cholinergic and adrenergic innervation of human penile tissue in diabetic and non-diabetic impotent males.

Penile tissue (consisting of corpus cavernosum and tunica albuginea) was obtained from 19 patients undergoing surgery for the implantation of penile prostheses. The tissue was examined for vasoactive intestinal polypeptide-like immunoreactivity in nerves, acetylcholinesterase-positive staining in nerves and noradrenaline content. Impotence was due to a variety of causes; 11 patients were classified as a 'non-neuropathic' group on the basis of their clinical history which included Peyronie's disease, vascular disease, hypertension and psychogenic impotence. Vasoactive intestinal polypeptide-like immunoreactive and acetylcholinesterase-positive nerves were present and the pattern and distribution were similar in each patient in this group. The noradrenaline content of the tunica albuginea was significantly lower than the corpus cavernosum (p less than 0.02), although there was a linear relationship between the noradrenaline contents of the two regions (r = 0.95, p less than 0.01). By comparison, a complete absence of vasoactive intestinal polypeptide-like immunoreactivity in nerves was observed in a patient with a cauda equina lesion. Five out of six diabetic patients studied revealed a marked reduction in vasoactive intestinal polypeptide-like immunoreactivity in nerves associated with the cavernous smooth muscle, while acetylcholinesterase-positive staining was reduced in three out of five diabetic patients studied. The noradrenaline content of the corpus cavernosum from diabetic patients was significantly lower (p less than 0.02) than that of the 'non-neuropathic' group. The noradrenaline content of the tunica albuginea, however, was similar in both groups. The results provide evidence that VIPergic, cholinergic and adrenergic nerves in the penis are affected in diabetes mellitus and thus may contribute to the development of impotence in diabetic patients.

Acetylcholinesterase↗

PubMed1987

Reduction of nerves containing vasoactive intestinal polypeptide and serotonin, but not neuropeptide Y and catecholamine, in cerebral blood vessels of the 8-week streptozotocin-induced diabetic rat.

The perivascular autonomic nerves of the major blood vessels on the ventral surface of the brain were studied in the streptozotocin-induced diabetic rat, an animal model for juvenile onset of diabetes. Histochemical and immunohistochemical techniques were used to determine the pattern and density of perivascular nerves containing catecholamine, 5-hydroxytryptamine (5-HT), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY). A significant reduction in the density and/or fluorescence intensity of 5-HT-immunoreactive nerves was observed in the circle of Willis and its main arterial branches namely: basilar, superior cerebellar, internal carotid, posterior communicating, middle cerebral and anterior cerebral arteries, while a significant reduction of VIP-immunoreactive nerves was observed in the internal carotid, middle cerebral and anterior cerebral arteries, but not in the basilar, superior cerebellar and posterior communicating arteries 8 weeks after the onset of diabetes. However, no changes were observed in the density of NPY- and catecholamine-containing nerves. The results are discussed in relation to autonomic neuropathy of the cerebral blood vessels in diabetes.

Animals↗

PubMed1986

Adrenergic innervation of vasa and nervi nervorum of optic, sciatic, vagus and sympathetic nerve trunks in normal and streptozotocin-diabetic rats.

Adrenergic nerves were studied in nervi nervorum and perivascular nerve plexus of vasa nervorum in whole-mount nerve sheath preparations of optic, sciatic and vagus nerves and in the paravertebral sympathetic chain in normal and streptozotocin-treated diabetic rats. A substantial or complete loss of fluorescent adrenergic fibres around blood vessels in the optic nerves was observed 8 weeks after induction of diabetes. This was in marked contrast to the increase in perivascular adrenergic fibres in the sciatic, vagus and sympathetic chain nerve trunks of the same animals at the same time. Assays of noradrenaline levels in whole nerve segments also showed that they were not biochemically detectable in the optic nerves but were significantly higher in the vagus of diabetic animals (P less than 0.05). There was also an increase in numbers of mast cells in the vicinity of vasa nervorum of diabetic nerves.

Adrenergic Fibers↗

PubMed1986

Enteric nerves in diabetic rats: electron microscopic evidence for neuropathy of vasoactive intestinal polypeptide-containing fibres.

Enteric nerves in the ileum of rats 8 weeks after streptozotocin-induction of diabetes were examined under the electron microscope before and after immunolabeling for vasoactive intestinal polypeptide (VIP). These studies have provided evidence of degenerative changes in the myenteric nerve fibres of diabetic rats, many of which were shown to contain VIP. It is suggested that VIP-ergic nerves in the gut may play a role in the development of gastrointestinal dysfunction in diabetes.

Animals↗