Search PubMed⌕ Search

Biomedical subjects

L Edvinsson

Publications and source records attributed to L Edvinsson.

At least 415 records · Page 23Linked to original sources
PubMed1981

Cerebral microembolization in the rat: changes in blood-brain barrier permeability and cerebral blood flow as related to the degree of ischemia.

Unilateral cerebral microembolism was performed in the rat by injecting calibrated, 50 micrometers in diameter, carbonized microspheres into the internal carotid artery. The events that follow brain ischemia due to cerebral embolization were studied by the analysis of the blood-brain barrier (BBB) function, the degree of regional cerebral blood flow (CBF) and the development of brain edema. Two hours after embolization there was no change in the brain water content. The local CBF (14C-ethanol technique) was only reduced in the ipsilateral hemisphere. Twenty-four hours after embolization the brain water content was increased significantly in the ipsilateral, but not in the contralateral hemisphere. Local CBF further decreased in the ipsilateral hemisphere and a reduction in flow was also observed in the contralateral hemisphere. Embolization led to an increase in the BBB permeability, analysed as regional penetrability of 3H-dextran and of Evans blue-albumin complexes, which was restricted to the side of the injection of the microspheres.

Animals↗
PubMed1981

Effects of prostaglandin E1, E2 and E2 alpha on isolated pial arteries of cat.

Responses to prostaglandin (PG), E1, E2, and F2 alpha were studied on isolated feline middle cerebral arteries. At resting state PGF 2 alpha produced strong dose-dependent contractions. PGE2 elicited weak relaxations at low concentrations, followed by powerful contractions at higher doses. PGE1 had little effect on resting pial vessels. The relative constrictory potency was PGF2 alpha greater than PGE2 greater than PGE1. During active tone, induced by administration of either potassium, norepinephrine, or 5-hydroxytryptamine, relaxations induced by PGE1 were enhanced, whereas PGE2-induced relaxations were unaffected. PGE1-induced relaxations were more pronounced when the active tension had been produced by administration of PGF2 alpha than with either of the vasoactive amines or potassium. This study demonstrates the importance of smooth muscle tone, and by what means this is achieved, when examining the response of PG's on cerebral blood vessels.

Animals↗
PubMed1981

VIP nerve fibres around peripheral blood vessels.

By immunocytochemistry nerve fibres containing vasoactive intestinal polypeptide (VIP) were demonstrated around many peripheral blood vessels in the cat. Such nerve fibres were particularly numerous around arteries in the upper respiratory, gastrointestinal and genito-urinary tracts. They were less numerous around large arteries and veins and seemed to be absent from the blood vessels in liver, spleen and kidney. VIP nerve fibres were few around blood vessels in skeletal muscle and absent in coronary arteries. Administration of VIP in vitro relaxed all arteries tested provided they had been given an increased tone, for instance by preincubation with PGF2 alpha. It is likely that VIP in vascular nerve fibres may participate in the regulation of systemic and local blood flow.

Animals↗
PubMed1981

Substance P: immunohistochemical localization and effect upon cat pial arteries in vitro and in situ.

1. Nerve fibres containing substance P immunoreactivity were present in the adventitia and the adventitia-media border of all cat cerebral arteries which were examined. Substance P immunoreactivity was most abundant in cerebral arteries from the rostral portion of the circle of Willis. 2. Substance P effected a dose-dependent relaxation of feline middle cerebral arteries which had been contracted with prostaglandin F2 alpha. The maximum relaxation (16 +/- 0.3 mN) was achieved with substance P at a concentration of 10-6 M. 3. In cats anaesthetized with alpha-chloralose, the perivascular microinjection of substance P effected dose-dependent increases in arteriolar calibre. The maximum increase in calibre (19 +/- 3%) was observed following the injection of 10(-6) M-substance P.

Animals↗
PubMed1980

Cerebral circulatory and metabolic effects of piribedil.

Two aspects of the cerebrovascular action of the putative dopaminergic agonist, piribedil, have been examined. The vasomotor responses of isolated feline middle cerebral artery to piribedil and its metabolite, S584, were first examined and the effects of piribedil upon cerebral blood flow, cerebral oxygen consumption and the electroencephalogram (EEG) were then investigated in anaesthetised baboons. Neither piribedil nor S584 displayed any marked vasomotor efficacy in vitro, with small changes in tension being observed only with large concentrations (greater than 10(-4) M). In the anaesthetised baboons, the administration of piribedil (0.1 and 1 mg/kg, i.v.) resulted in significant increases in cerebral blood flow (40 +/- 10% and 49 +/- 14%, respectively) (mean +/- S.E.M.) and cerebral oxygen consumption (13 +/- 10% and 17 +/- 6%) which were accompanied by an increase in low voltage fast activity of the EEG. Prior administration of the putative dopaminergic antagonist, pimozide (0.5 mg/kg), which itself was without significant effect upon cerebral blood flow and oxygen consumption, prevented the cerebral circulatory, metabolic and EEG alterations induced by piribedil (1 mg/kg). It would appear likely that the action of piribedil upon cerebral metabolic activity was principally responsible for the increases in cerebral tissue perfusion which followed its administration.

Animals↗
PubMed1980

VIP (vasoactive intestinal polypeptide)-containing nerves of intracranial arteries in mammals.

Immunohistochemical and radioimmunochemical investigations have shown, in various species, the occurrence of numerous nerve fibres containing vasoactive intestinal polypeptide (VIP) in connection with blood vessels of the central nervous system. Pial arteries from pig, cat, and rat have the richest supply of VIP nerve fibres; those of cow, dog guinea pig and hamster have an intermediary number of nerves, while only few are found in pial arteries from the monkey, rabbit, gerbil, and mouse. The regional variation in VIP-nerve density follows the order: cerebral arteries greater than basilar greater than vertebral greater than spinal cord arteries. Unilateral extirpation of either the pterygopalatine or the superior cervical ganglia does not affect the amount or distribution of VIP fibres in the wall of brain vessels of the ipsilateral side. Measurement of the VIP content by radioimmunoassay shows mean concentrations in the pial arteries varying between 19 and 82 pmol/g tissue wet weight. Regional and species variations in measured VIP levels are similar to the variations in distribution of immunoreactive nerve fibres.

Animals↗
PubMed1980

Vincristine reduces damage of the blood-brain barrier induced by high intravascular pressure.

A reversible opening of the structural blood-brain barrier (BBB) was accomplished in rats by rapidly increasing the hydrostatic pressure either through forced intracarotid infusion of autologous blood or i.v. administration of angiotensin, whose effect was exaggerated by previous injection of the vasodilator, papaverine. The extent of barrier damage was evaluated in terms of the extravasation of Evans blue-albumin complex or the brain uptake of circulating [14C]inulin. Pretreatment of the animals with the antimitotic agent, vincristine, significantly reduced the barrier damage. This is interpreted as an effect of vincristine on intracellular microtubule systems, which may be involved in the vesicular transport across the endothelial cells of brain microvessels.

Angiotensin II↗
PubMed1980

Cerebrovascular sympathetic denervation and blood-brain barrier function in conscious rats.

Electrical stimulation of the sympathetic nerves to the cerebrovascular bed enables the resistance vessels to better withstand a high blood pressure in terms of blood-brain barrier integrity. Sympathetic denervation could hence be expected to lead to a decrease in cerebrovascular tone and increased vulnerability of the blood-brain barrier. In the present study acute hypertension was induced in conscious unrestrained rats by administration of angiotensin or bicuculline. The albumin leakage into the brain, as studied by Evans blue-albumin and 125I labelled human serum albumin, was not enhanced in acutely or chronically sympathectomized rats compared to controls.

Angiotensin II↗
PubMed1980

Cerebral circulatory and metabolic effects of vasoactive intestinal polypeptide.

Two aspects of the action of vasoactive intestinal polypeptide (VIP) within the cerebral vascular bed have been examined. First, in anesthetized rats, the vasomotor responses of individual pial arterioles on the convexity of cerebral cortex to the perivascular microinjection of vasoactive intestinal polypeptide were examined and, second, in anesthetized baboons, the effects of VIP on cerebral blood flow, cerebral oxygen consumption, and the electroencephalogram (EEG) were investigated both prior to and following the osmotic opening of the blood-brain barrier. The perivascular microinjection of VIP resulted in statistically significant increase in arteriolar caliber in the concentration range 10(-9) to 10(-6) M. For example, arteriolar caliber was increased by 22 +/- 3% (mean +/- SE) following the injection of VIP (10(-8) M). In the second series, in baboons, the intracarotid infusion of vasoactive intestinal polypeptide (10(-11) mol/min) did not affect cerebral blood flow, cerebral oxygen consumption, or the EEG under normal circumstances. If the same concentration of vasoactive intestinal polypeptide was administered following hypertonic opening of the blood-brain barrier, cerebral blood flow and oxygen consumption were both elevated (by 37 +/- 7% and 28 +/- 10%, respectively), accompanied by increased EEG activity.

Animals↗
PubMed1980

Cholinergic inhibition of sympathetic vasoconstrictor tone in the cerebrovascular bed mediated by nicotinic-type receptors.

The cholinergic influence on the cerebrovascular bed was studied in cats and rabbits using a combination of in vitro and in vivo approaches. Isolated pial arteries were superfused with 3H-norepinephrine, and the efflux of tritium was studied under various conditions of transmural electrical stimulation of the perivascular sympathetic nerves. Field stimulation increased the radioactivity in the efflux in a frequency-dependent manner. The amount of tritium overflow (of which approximately 70% represents liberated radioactive norepinephrine) from the nerves during stimulation was enhanced by hexamethonium, the effect being inhibited by nicotine or acetylcholine. This action of nicotine and acetylcholine was counteracted by hexamethonium (but not by atropine). Carbachol infusion under in vivo conditions increased blood flow in the caudate nucleus as measured by thermoclearance. This effect was inhibited by atropine. Postganglionic stimulation of the cervical sympathetic chain above the superior cervical ganglion produced, in itself, a reduced local cerebral blood flow. The response (but not the flow reduction obtained by exogenous norepinephrine) was diminished during infusion with carbachol. The inhibition, amounting more than 50%, of the sympathetic nerve action on CN blood flow was not affected by atropine. It is concluded that (a) there are direct cholinergic dilator mechanisms in the cerebrovascular bed mediated by muscarinic-type of cholinergic receptors in the vascular smooth musculature, and (b) the perivascular adrenergic nerve terminals possess nicotinic-type of cholinergic receptors mediating an ihibition of the local norepinephrine release, probably through an action by the cholinergic nerve terminals, which run parallel to and in close association with the adrenergic axons separated only by a 25 nm distance.

Animals↗
PubMed1980

5-Hydroxytryptamine receptors. Contractile activity and mode of inhibition by methysergide in mammalian intracranial and extracranial vessels.

The contractile effect of 5-HT on intra- and extracranial arteries from rabbit, cat, dog and man and its interaction with methysergide was investigated. ED50 and EAm values for 5-HT from both types of arteries differed. Intracranial arteries stimulated by 5-HT were more sensitive to methysergide than extracranial arteries. In intracranial vessels the methysergide antagonism is non-competitive while in extracranial it is competitive. These differences might suggest a heterogeneity of 5-HT receptors located within the cranial circulation.

Animals↗
PubMed1979

Pharmacological characterization of GABA receptors mediating vasodilation of verebral arteries in vitro.

GABA (gamma-aminobutyric acid) produced a dose-dependent dilation of isolated cat and dog cerebral artery segments which had been given an active, tonic contraction by either prostaglandin F2 alpha or serotonin. No effect of GABA on extracranial blood vessels was observed. The GABA-induced dilation could be blocked in a dose-dependent manner by either bicuculline or picrotoxin. The latter agent appeared to act as a competitive antagonist. GABA agonists muscimol, imidazoleacetic acid, delta-aminovaleric acid, (+/-)gamma-amino-beta-hydroxybutyric acid, and beta-alanine also relaxed actively contracted cerebral arteries dose-dependently. The relative potency of these agonists was consistent with that established for GABA receptors on neurons and invertebrate striated muscle. GABA was also tested on two human cerebral arteries and found to cause a small dilation. The results support the existence of a cerebrovascular GABA receptor which may mediate an interaction between GABA and the cerebral circulatory system.

Animals↗
PubMed1979

Histofluorescence study on monoamine entry into the brain before and after opening of the blood-brain barrier by various mechanisms.

The relationship between exogenous, circulating monoamines to the wall of cerebral microvessels, and the entrance of these amines into the cerebral parenchyma was studied by the formaldehyde histofluorescence technique in rats. No monoamine fluorescence could be detected in the wall tissue of the microvessels (pericytes and andothelial cells) unless either MAO or COMT were inhibited; these are integral to the blood-brain barrier mechanisms to monoamines. After transient opening of the morphologic blood-brain barrier by either a hypertonic of hypertensive insult, the amine fluorescence in the walls of the microvessels was intensified compared to that which was noted after monoamine oxidase inhibition by itself. Following opening of the structural blood-brain barrier, the circulating amines also passed through into the neuropil where they were concentrated within neurons, as demonstrated by prior depletion of endogenous monoamine transmitters by reserpine. Thus, both enzymatic and morphologic mechanisms in the blood-brain barrier ar involved in impeding the passage of monoamines into the cerebral parenchyma.

Animals↗
PubMed1979

Effects of increasing arterial pressure on cerebral blood flow in the baboon: influence of the sympathetic nervous system.

The influence of stimulation of the cervical sympathetic chain on the response of cerebral blood flow to hypertension induced by the intravenous infusion of angiotensin was studied in anaesthetised baboons. Cerebral blood flow was measured by the intracarotid 133Xenon injection technique. Possible lesions of the blood-brain barrier were studied by injecting Evans blue towards the end of the experiment and ischaemic brain damage was assessed following perfusion fixation. In a control group of five baboons blood flow increased by 53 +/- 9% (mean +/- S.E.) from the base line values in the arterial pressure range 130-159 mm Hg. In four baboons subjected to unilateral sympathetic stimulation flow increased by 16 +/- 4% in the same pressure range. In three baboons subjected to bilateral sympathetic stimulation there were no significant increases in flow until the arterial pressure had increased above 159 mm Hg. Disruption of the blood-brain barrier in the parietooccipital regions was only seen in the control animals but not in the stimulated baboons. Ischaemic brain damage was not observed with the exception of one small lesion in a single stimulated baboon. These findings provide strong support for the observations of Bill and Linder (1976) that activation of the cervical sympathetic can modify the level at which breakthrough of cerebral blood flow occurs in association with systemic hypertension.

Angiotensin II↗
PubMed1979

5-HT antagonism on cerebral and common carotid arteries by the 5-HT uptake inhibitors femoxetine and paroxetine.

The 5-hydroxytryptamine (5-HT) antagonism of methysergide was compared with that of the phenylpiperidine 5-HT uptake inhibitors, paroxetine and femoxetine, using two different models; the isolated cat middle cerebral artery and the common carotid artery of pithed rat perfused with the rat's own blood (autoperfusion). The extracorporeal circulation consisted of about 1.5 ml blood, which was temperature regulated to 36-38 degrees at the inlet to the carotid vessel by an automatic thermistor coupled heating system. In these experiments systemic blood pressure responses and perfusion pressure responses to 5-HT were recorded simultaneously. The 5-HT induced contractile response of the middle cerebral artery was reduced in a noncompetitive way by both uptake inhibitors at concentrations above 0.3 microM which is about 100 times the concentration needed for methysergide. In autoperfusion experiments inhibition was observed only at 5 mg/kg of both drugs. However, methysergide 0.001 mg/kg totally abolished all 5-HT responses. The uptake inhibitors can therefore be described as weak 5-HT antagonists.

Animals↗