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Biomedical subjects

L Edvinsson

Publications and source records attributed to L Edvinsson.

539 records · Page 30Linked to original sources
PubMedDate not supplied

Distribution and effects of neuropeptide Y, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide in human middle meningeal arteries: comparison with cerebral and temporal arteries.

A sparse to moderate supply of nerve fibers containing neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal polypeptide (VIP-LI), substance P (SP-LI), and calcitonin gene-related peptide (CGRP-LI) was demonstrated in the walls of human middle meningeal arteries. Comparison with similar studies on human cerebral and temporal arteries indicated a similar distribution and density. The immunoreactive material in all three arterial regions was characterized by reversed-phase high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA). The major peak of NPY-LI, VIP-LI, SP-LI, and CGRP-LI in each extract eluted approximately with the same elution volume as that of the corresponding synthetic analogues. The concentration of NPY in the middle meningeal arteries was lower as compared to the temporal arteries. Low concentrations of SP-LI and CGRP-LI were found in the middle meningeal arteries as compared to the cerebral arteries. In isolated ring segments of human middle meningeal and cerebral arteries, NPY caused vasoconstriction but did not potentiate the contractile response of noradrenaline. In the temporal artery, NPY did not induce contraction but potentiated the vasoconstrictor response to noradrenaline. Vasoactive intestinal polypeptide, peptide histidine methionine-27, SP, neurokinin A, and CGRP relaxed all three types of cephalic arteries. The peptide effects were not antagonized by propranolol, atropine, or cimetidine. Comparison of the responses to VIP and SP of vessels from the different regions showed a similar pattern of reactivity. The response to SP was slightly (p less than 0.05) more potent, whereas the responses to CGRP were less potent in the middle meningeal as compared to that in cerebral (p less than 0.005) vessels.

Acetylcholine↗
PubMedDate not supplied

Immunohistochemical demonstration of APP (avian pancreatic polypeptide)-immunoreactive nerve fibres around cerebral blood vessels.

Nerve fibres containing immunoreactive avian pancreatic polypeptide (APP) were demonstrated in the wall of cerebral blood vessels from several species. Pial arteries of chicken, mouse, rat, guinea-pig, cat and dog had a dense supply of APP fibres while APP fibres were less numerous in rabbit, cow and monkey. The APP-immunoreactive fibres were more numerous in the rostral part of the circle of Willis than around more caudally located pial vessels. Immunoreactive fibres were also seen in the wall of pial vessels of the spinal cord, as shown in the cat. Extirpation of the superior cervical sympathetic ganglion was followed by a marked reduction in the number of APP-containing fibres on the ipsilateral side of the brain.

Adrenergic Fibers↗
PubMedDate not supplied

Influence of external light conditions on norepinephrine levels in organs innervated by sympathetic nerves from different levels.

Rat tissues receiving their sympathetic innervation from different levels were studied for changes in their norepinephrine level after maintaining the animals for 2 weeks under various lighting conditions. Constant darkness resulted in a doubling of the norepinephrine concentration in iris and a significant increase also in the pia-arachnoid when compared to the tissues from animals kept in alternating light/darkness conditions. Also continuous light gave higher norepinephrine concentrations in the pia-arachnoid. None of the light conditions studied affected cardiac norepinephrine. Norepinephrine levels in vas deferens were reduced after constant light and increased after constant darkness, compared to light/dark conditions. It is concluded that norepinephrine only in tissues innervated from the superior cervical sympathetic ganglia is influenced by external light stimuli, and that the norepinephrine changes in vas deferens are secondary effects of the hormonal alterations produced by continuous light and darkness, respectively, and affecting the entire reproductive tract.

Adrenergic Fibers↗
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Reduced noradrenaline uptake and retention in cerebrovascular nerves associated with angiographically visible vasoconstriction following experimental subarachnoid hemorrhage in rabbits.

Rabbits were injected with 1-2 ml autologous blood into the chiasmatic and basal cisterns to stimulate subarachnoid hemorrhage. Selective vertebral angiography performed at various time-periods following blood injection showed a 27 per cent reduction in basilar artery diameter within 3-5 days, followed by normalization so that pre-injection size was regained within 26 days after the treatment. Formaldehyde histofluorescence of the major basal pial arteries showed almost 75 per cent reduction in number and fluorescence intensity of visible perivascular adrenergic nerves at 3-7 days following blood injection. The noradrenaline fluorescence in a normal number of nerves returned to control values at 26 days after treatment. The noradrenaline reduction in the perivascular nerves was confirmed in fluorometric determinations. The presence of cisternal blood markedly impaired the neuronal uptake of 3H-noradrenaline at 3 days following the injection. The transmitter uptake had normalized 2 weeks later. The impaired neuronal uptake of noradrenaline in the presence of cisternal blood is in accordance with the net reduction in transmitter of the perivascular nerves, and may provide one pathophysiological factor in the development of angiographically visible vasoconstriction, having a time-course resembling that of the functional changes in the perivascular adrenergic nerves.

Adrenergic Fibers↗
PubMedDate not supplied

Renal arterial reactivity to potassium, noradrenaline, and neuropeptide Y and association with urinary albumin excretion in the diabetic rat.

A changed vasomotor reactivity of renal arteries may lead to defect autoregulation of renal hemodynamics with damage of diabetic kidneys. Eleven streptozotocin-induced diabetic male Wistar rats were daily treated with insulin in order to achieve a blood glucose of 21 mmol/L. Seventeen age and gender-matched rats served as controls. After 50 days, the kidneys were rapidly removed, arteria renalis and the first branches of the intrarenal arteries were dissected free. The arterial reactivity was tested with a sensitive in vitro method. The reactivity to noradrenaline was tested by cumulative application (10(-9) to 3 x 10(-4) M) before and after a single concentration of neuropeptide Y (NPY). Potassium (60 mM) and noradrenaline induced a strong contraction of all arteries with similar response in diabetic and control rats. The effect of noradrenaline after NPY was unchanged in renal vessels of control rats, whereas it was diminished in intrarenal vessels for both diabetic and control rats. Similarly, a diminished response was found for renal arteries in diabetic rats, an effect which was related to the level of blood glucose (r = 0.62, 2p = 0.04). The urinary excretion rate of albumin in the diabetic rats was related to the largest noradrenaline induced contraction (r = 0.71, 2p = 0.01) of renal but not of intrarenal arteries. In conclusion, there was no difference in potassium and noradrenaline evoked contractions in renal and intrarenal arteries in diabetic and control rats. NPY decreased the contractile response to noradrenaline. The high blood glucose slightly increased this effect of NPY.

Albuminuria↗
PubMedDate not supplied

Central serotonergic nerves project to the pial vessels of the brain.

Serotonin is strongly implicated in the aetiology of several cerebrovascular (circulatory) diseases, including stroke, migraine and vasospasm. Previous studies have suggested the existence of an indoleaminergic system of perivascular nerves in large cerebral arteries of the lamprey. In addition, some authors have observed that cerebral arteries (such as the vertebrobasilar system of the rabbit) and microvessels may take up serotonin and 5-hydroxytryptophan in various species. However, neither large cerebral arteries nor microvessels (primarily capillaries) directly control, or change, cerebral blood flow; as in other vascular beds, it is the arterioles and small arteries that are the major resistance elements. We report here on the presence of a central serotonergic innervation of pial arteries and arterioles in the rat, using immunocytochemical and neurochemical techniques. The fibres seem to have a central neuronal origin, emanating from both median and dorsal raphé nuclei. This perivascular serotonergic innervation may have a role both in the normal regulation of the cerebral circulation and in pathological conditions.

Animals↗
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Circulating levels of neuropeptides (CGRP, VIP, NPY) in patients with fulminant hepatic failure.

The present study investigated the circulating levels and cerebral fluxes of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) and their relation to cerebral blood flow (CBF) during normoventilation and hyperventilation in patients with fulminant hepatic failure (FHF). Sixteen patients with FHF were studied and compared to six patients with cirrhosis of the liver. CBF was measured by the (133)Xe wash-out technique. Blood samples were obtained simultaneously from the artery and internal jugular bulb. Concentrations of CGRP and VIP were higher in FHF than in cirrhosis, 87 (55-218) vs. 29 (21-42) pmol/L, and 11 (6-29) vs. 5 (3-9)pmol/L, respectively. NPY was normal, none of the measures were related to CBF, and there was no detectable net brain fluxes. Hyperventilation did not alter any of the measures. CGRP and VIP in FHF seem to reflect hemodynamic changes in the systemic rather than in the cerebral circulation.

Adult↗
PubMedDate not supplied

Joint 1994 Wolff Award Presentation. Peripheral and central trigeminovascular activation in cat is blocked by the serotonin (5HT)-1D receptor agonist 311C90.

Migraine headache involves the activation of trigeminal afferents that are predominantly found in the first or ophthalmic division of the nerve. The headache is often pounding and the connections of the trigeminal nerve, the trigeminovascular system, have therefore been implicated in the pathophysiology of migraine and studied extensively. Considerable attention has been given to the peripheral ramifications of the system as a possible locus of action for anti-migraine drugs while little attention has been focused upon possible central sites of action. It has been shown that certain peptides can act as markers for the trigeminal system, in particular calcitonin gene-related peptide (CGRP), and that CGRP is elevated in migraine. We have employed an animal model for activation of the trigeminovascular system to evaluate a new antimigraine compound, 311C90, that may have central and as well as peripheral trigeminal actions. Cats were anesthetized by halothane induction and alpha-chloralose maintenance (60 mg/kg, intraperitoneal), intubated, paralyzed and ventilated. Biparietal craniotomies were carried out to measure cerebral blood flow using laser Doppler flowmetry (CBFLDF). The external jugular vein was cannulated and blood drawn, centrifuged and frozen until processing. Stimulation of the trigeminal ganglion resulted in a mean maximum increase in CBFLDF of 39 +/- 5% at 20/s. The 5HT1 agonist 311C90 was administered intravenously in two doses (30 and 100 micrograms/kg) to cover the range of doses likely to be effective clinically. At each dose the CBFLDF effect of trigeminal ganglion stimulation was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Neuropeptide Y in sympathetic co-transmission: recent advances in the search for neuropeptide Y antagonists.

Since the discovery of neuropeptide Y which is co-stored and co-operate with noradrenaline (NA) in sympathetic nerve fibers, several scientific groups have searched for structures with neuropeptide Y antagonistic properties. Research has mainly focused on various peptide fragments which originate from or are related to the neuropeptide Y sequence. Some non-peptide antagonists have been proposed but they are mostly of low potency and non-selective. Our recent observations that alpha-trinositol (D-myo-inositol 1.2.6-trisphosphate) is an inhibitor of neuropeptide Y effects will hopefully lead to the development of useful non-peptide neuropeptide Y inhibitors. As a novel approach the highly selective approach of down-regulating neuropeptide Y receptors with antisense oligodeoxynucleotides is also discussed. Neuropeptide Y antagonistic agents would help us to understand the physiological role of neuropeptide Y and may serve as useful medication in circulation disorders.

Animals↗
PubMedDate not supplied

Somatostatin and neuropeptide Y in cerebrospinal fluid: correlations with severity of disease and clinical signs in Alzheimer's disease and frontotemporal dementia.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common types of progressive neurodegenerative disorder in our catchment area. The distribution of cortical degeneration in FTD is mainly the reverse of that in AD, while there are both differences and similarities in the clinical characteristics. Somatostatin and neuropeptide Y (NPY) are neuropeptides with a widespread distribution in the human cerebral cortex. Somatostatin is involved in the regulation of hormone release from the anterior pituitary and may act as a neurotransmitter-modulator. NPY is a potent anxiolytic neuropeptide. Somatostatin and NPY coexist in the cerebral cortex, basal ganglia and in amygdaloid complexes. The present study of AD (n = 34) and FTD (n = 22) analyses the cerebrospinal-fluid (CSF) levels of somatostatin-like immunoreactivity and NPY-like immunoreactivity and correlates their levels to 54 different clinical items, such as restlessness, anxiety, irritability and depression. The CSF levels of the two neuropeptides somatostatin and NPY were significantly correlated in FTD (p < 0.02), but not in AD. Several significant correlations to the clinical signs were found: in AD disorientation and dyspraxia, and in FTD agitation, irritability and restlessness. Somatostatin showed a significant negative correlation with severity of dementia in AD (p < 0.013).

Adult↗
PubMedDate not supplied

Tacrine treatment modifies cerebrospinal fluid neuropeptide levels in Alzheimer's disease.

Biochemical and histochemical studies have demonstrated a widespread deficit in the activity of acetylcholinesterase (AChE) in the brains of patients with Alzheimer's disease (DAT). Multiple disturbances in several transmitter systems have been found. The most consistent neurochemical changes in DAT are reductions in the cholinergic system. The major pharmacological approach today in DAT is based on the cholinergic theory assuming that acetylcholine has a major cortical impact on cognitive processes. Tetrahydroaminoacridine (THA, tacrine) is a centrally active reversible acetylcholinesterase inhibitor. A large number of trials have been performed in patients with DAT. This article was to evaluate whether THA treatment induced neuropeptide alteration in DAT before and after 1 year on oral THA treatment.

Aged↗
PubMedDate not supplied

Long-term effects of tacrine on regional cerebral blood flow changes in Alzheimer's disease.

UNLABELLED: Regional cerebral blood flow (rCBF) was studied in patients with Alzheimer's disease (AD) before and after 14 months of tacrine treatment. The treated group was compared with an identical reference group of untreated AD patients. At baseline the two groups showed an identical rCBF and mean hemispheric blood flow. After 14 months the tacrine-treated patients showed a stable rCBF level and a significant increase in rCBF in the central-parietal regions, compared to the untreated reference group, who showed typical AD reductions in rCBF in these regions. CLINICAL OUTCOME: 7 of 9 patients in the tacrine group were clinically unchanged or slightly improved during the study time. In the untreated group 8 of 11 patients had deteriorated in clinical assessments and none had improved. Long-term tacrine treatment in Alzheimer's disease may delay the progression of symptoms.

Aged↗
PubMedDate not supplied

Neuropeptides in cerebrospinal fluid of patients with Alzheimer's disease and dementia with frontotemporal lobe degeneration.

The two major primary degenerative dementias, dementia of Alzheimer type (DAT) and frontal lobe degeneration of non-Alzheimer type (FLD) have several clinical features in common but also many symptoms that differ. In a clinical material of 80 patients with either of the two forms of dementia (DAT = 39, FLD = 41) we have studied the levels of neuropeptides in the cerebrospinal fluid (CSF) in order to find biochemical markers for CNS affection. The dementia forms were evaluated by careful clinical analysis, psychometric testing and measurement of regional cerebral blood flow. Approximately one third of the subjects died during the completion of the study and neuropathology was performed, confirming the diagnoses. We observed reductions in the CSF levels of antidiuretic hormone and somatostatin in both DAT and FLD. A strong tendency to reduction was noted for neuropeptide Y (NPY). There was a correlation with the duration of disease demonstrating a significant reduction in NPY levels in subjects with DAT. Most notably there was a strong reduction in the levels of delta sleep inducing peptide (DSIP) in DAT cases only. The levels of DSIP in FLD were the same as in controls. The reverse was found for corticotropin releasing factor (CRF) which had a significant reduction in FLD patients but not in those with DAT. The present study indicates a difference in the CSF levels of neuropeptides, observations that these may serve as biochemical markers which differentiate DAT and FLD.

Adult↗
PubMedDate not supplied

Adenine compounds: cerebrovascular effects in vitro with reference to their possible involvement in migraine.

Adenosine and adenine compounds (AMP, cyclic AMP, ADP and ATP) markedly dilated feline and human pial arteries in vitro, the effect being more prominent with increasing tone of the vessel (active tonic contraction induced by prostaglandin F 2 alpha or serotonin). In contrast, the various adenine compounds were unable to produce any dilation of extracranial arteries tested (branches of lingual, external maxillary, and superficial temporal arteries). The degree of dilatation depended upon the perivascular potassium concentration, so that low potassium increased Emax and reduced ED50 values. Possible involvement of adenine compounds in the vasodilatory phase of the migraine attack is discussed.

Adenosine↗
PubMedDate not supplied

Influence of serotinin and norepinephrine on flow capacity/pressure characteristics of feline isolated cerebral arteries.

Isolated feline pial vessel segments (250-400 microns in diameter, 4 mm long) were mounted in Krebs solution in organ baths on L-shaped metal holders connected to pressure transducers. From the distance between the outer limits of the wires (f) and the force recorded by the transducers (F), the transmural pressure and the flow capacity were calculated. Changes in these parameters were produced by increasing the distance between the holders. Norepinephrine (10(-5) M) and serotonin (10(-6) M) were added to the tissue bath at different resting wall tensions. Both norepinephrine and serotonin resulted in contractile responses that were maximal at a resting wall tension of 2 nM/mm. Norepinephrine and serotonin displaced the flow capacity/pressure curve to the right up till at least 112 mm Hg, indicating a displacement of the autoregulatory range to the right.

Animals↗
PubMedDate not supplied

Sympathetic innervation of cerebral arteries: prejunctional supersensitivity to norepinephrine after sympathectomy or cocaine treatment.

The inactivation of the norepinephrine transmitter in the region of the adrenergic receptor is one important function of the sympathetic nerve terminals innervating blood vessels. This capacity was tested on isolated cat's middle cerebral artery (MCA) by recordings of the contractile response induced by norepinephrine at various stages after sympathectomy (excision of the superior cervical ganglion). Within three days after denervation, when fluorescence microscopy revealed a disappearance of neuronal norepinephrine in the vessel wall, there was a threefold increase in sensitivity of the test system which was not further enhanced at two weeks. This, and the finding of a similar amount of sensitization (of non-denervated vessels) to norepinephrine or tyramine after cocaine treatment, showed that a prejunctional type of sensitivity had developed. The sympathetic denervation did not influence the dose-response curve obtained with acetylcholine, supporting the specific nature of the supersensitivity reaction only to the sympathetic transmitter. Half a year after sympathectomy the sensitivity of the pial arteries to norepinephrine returned to control levels despite the absence of reinnervation, indicating that postjunctional changes also occurred. The findings offer further evidence for a functional role of the sympathetic nerves supplying intracranial arteries and show that the mode of innervation resembles that found in peripheral vessels.

Acetylcholine↗