Search PubMed⌕ Search

Biomedical subjects

L Edvinsson

Publications and source records attributed to L Edvinsson.

At least 397 records · Page 22Linked to original sources
PubMed1983

Mechanical properties of rat cerebral arteries as studied by a sensitive device for recording of mechanical activity in isolated small blood vessels.

A sensitive device for recording of mechanical activity in isolated small blood vessels with calibres down to 100 microns is described. This equipment was used to examine the mechanical properties of rat cerebral arteries. The ultrastructure of the preparations was investigated by light-, transmission, and scanning electron-microscopy. In general the walls of the middle cerebral and basilar arteries consisted of 3 layers of smooth muscle cells, which occupied approximately 80% of the total wall thickness. The present technique preserved the integrity of the vessel wall and caused no observable damage to the smooth muscle or endothelial cells. Neither the basilar nor the middle cerebral arteries developed spontaneous phasic contractions under standard conditions. Potassium excess (124 mM) induced a biphasic contractile response characterized by a fast and partly transient increase in tension (phase A), followed by a slowly developing sustained contraction (phase B). The responses to K+ were strong, highly reproducible and not influenced by pH changes in the range 6.9-7.8, making K+-stimulation suitable for testing of vascular contractility. Length-tension measurements were performed on relaxed and K+-activated basilar arteries. The mechanical behaviour of the vessels conformed to a sliding-filament model of muscular contraction. Using the "Maxwell model" of a muscle, the length at which the contractile element produced maximum active tension was established. The passive wall tension at this length (approximately 1 mN/mm) averaged only about 20% of the total wall tension the arteries were capable of producing when activated by K+. Under isometric conditions the K+-contracted basilar artery developed a maximum active wall stress of approximately 240 mN/mm2. In the light of the mechanical data obtained from the length-tension measurements, the optimum resting wall tension for registration of vascular responses is discussed. It appears that the present in vitro system can be of great value in investigations of the smooth muscle function in small blood vessels.

Animals↗
PubMed1983

Pharmacological characterization of postjunctional alpha-adrenoceptors in isolated feline cerebral and peripheral arteries.

The vascular alpha-adrenoceptors in isolated feline cerebral, lingual and mesenteric arteries were characterized and compared. In the middle cerebral artery the relative order of potency for agonists was: clonidine greater than oxymetazoline greater than noradrenaline greater than phenylephrine which indicates that the postjunctional alpha-receptor in this vessel is of alpha 2-type. This view is further supported by the finding that yohimbine, but not prazosin, had a potent, mainly competitive blocking action. In peripheral arteries, clonidine was without effect. In these vessels, the potency difference between phenylephrine and oxymetazoline was more than 40 times less than in cerebral vessels. The pA2-values for prazosin correlated well with pA2-values found for the interaction of this drug with alpha 1-receptors in a variety of other tissues, thus suggesting the occurrence of an alpha 1-receptor in these arteries. However, the pA2-values for yohimbine and rauwolscine correlated well with an alpha 2-receptor, suggesting also the presence of alpha 2-receptors. Schild plots for prazosin and rauwolscine in lingual arteries displayed slopes significantly lower than unity, which also supports the view of a mixture of alpha 1- and alpha 2-receptors in these vessels. However, the Schild plots for the antagonists in mesenteric arteries did not differ significantly from unity, a finding possibly indicating the presence of an alpha-receptor unable to differentiate between substances that in other tissues act preferentially on alpha 1- or alpha 2-receptors.

Animals↗
PubMed1983

Effect of sympathetic nerve stimulation and adrenoceptor blockade on pial arterial and venous calibre and on intracranial pressure in the cat.

Pial arterial and venous calibre were continuously recorded through a closed cranial window preparation during cervical sympathetic nerve stimulation in 10 cats before and after alpha- and beta-adrenoceptor blockade. In addition, the intracranial pressure (ICP) was simultaneously recorded in 4 of the cats. Under resting conditions 33 arteries (mean diameter 130 micron) constricted by 11.7 +/- 0.8% and 80 venous portions (mean diameter 152 micron) constricted by 13.7 +/- 0.7% during sympathetic nerve stimulation. ICP decreased simultaneously by 16.5 +/- 6.2%. Administration of the alpha-adrenoceptor antagonist phenoxybenzamine i.v. (1.5 mg X kg-1) abolished the reduction of ICP and markedly reduced, but did not completely abolish, the constrictor response of arteries and veins. The beta-adrenoceptor antagonist propranolol (1.5 mg X kg-1) did not significantly alter the reduction of ICP or the response of pial veins and small arteries, whereas the response of arteries with a diameter greater than 150 micron was attenuated. It is concluded that the constriction of pial veins and arteries during sympathetic stimulation is mediated predominantly via alpha-adrenoceptors. The sympathetic nerves of cerebral blood vessels may have stronger influence on the cerebral capacitance than on resistance vessels under normotensive and normocapnic conditions.

Adrenergic alpha-Antagonists↗
PubMed1983

Characterization of histamine receptors in cat cerebral arteries in vitro and in situ.

Histamine is probably a mediator of vascular responses in the brain, but there is little experimental evidence for its importance in this role. By using both in vitro and in situ techniques, we have studied responses of cat pial arteries to stimulation of histamine receptors by pharmacological agents. In vitro, histamine and 2,2-pyridylethylamine (PEA, H1 agonist) caused contraction of resting arteries while impromidine (H2 agonist) was without effect. The PEA-induced constriction was blocked by the histamine H1 antagonist, mepyramine. When the arteries were precontracted (by 3 X 10(-6) M prostaglandin F2 alpha), however, all three agents caused vascular relaxation with an order of effectiveness as follows: histamine = impromidine much much greater than PEA. The responses of histamine and impromidine were reduced by the H2-antagonists, metiamide or cimetidine. Schild plots for the H2 receptor antagonists resulted in pA2 values of 6.90 and 7.03 for metiamide and cimetidine, respectively. In situ, neither agonist caused pial arterial constriction. Impromidine was considerably more effective than PEA in producing arterial dilatation. Metiamide reduced the effect of impromidine, whereas the dilatation of PEA was reduced by mepyramine. Dilatations resulting from PEA persisted in the presence of metiamide. Our results are consistent with the hypothesis that histamine H2 receptors are present in cerebral vascular smooth muscle as identified both in vitro and in situ. Indications for the additional presence of H1 receptors are, however, weak.

Animals↗
PubMed1982

Characterization of 5-hydroxytryptamine receptors in human temporal arteries: comparison between migraine suffers and nonsufferers.

An increase in the sensitivity of temporal arteries to 5-hydroxytryptamine (5-HT) has repeatedly been suggested on indirect evidence as an essential component of a migraine attack. We examined the 5-HT reactivity of isolated human temporal arteries removed from migraine sufferers and from patients operated on because of cerebral disorders. 5-HT constricted these vessels in a concentration-dependent manner, the response being attenuated by 10-8 tp 10-6 M methysergide. There was no difference in reactivity to 5-HT or methysergide between vessels from the two patient groups. The pA2 value calculated for methysergide in controls was 7.8 +/- 0.1 and in migraine patients, 7.6 +/- 0.2, which closely agreed with data obtained graphically using Schild plots: 7.8 amd 7.7. respectively. No difference existed between the patient groups due to age or sex. Thus, clear evidence has been obtained demonstrating the presence of 5-HT receptors in human temporal arteries, although we could observe no difference in the character of the 5-HT receptors between migraine patients and controls.

Adolescent↗
PubMed1982

Perivascular nerves in the feline carotid rete.

Numerous nerve fibres containing acetylcholinesterase and noradrenaline, as well as avian pancreatic polypeptide-, vasoactive intestinal peptide-, or substance P-like immunoreactivity are observed around arteries in the external carotid rete of the cat. The nerves are located in the adventitial layer close to the media. It is possible that adrenergic, cholinergic and peptidergic nerve fibres may have a strong neurogenic influence on the rete blood vessels.

Acetylcholinesterase↗
PubMed1982

Comparison of the effects of potassium and pH on the calibre of cerebral veins and arteries.

The vasomotor response of individual pial veins and arteries on the convexity of the cerebral cortex to perivascular microinjection of mock cerebrospinal fluid (CSF) containing various concentrations of potassium (K+) and of various pH (achieved by altering the bicarbonate, HCO-3 concentration) have been examined in cats anaesthetised with alpha-chloralose. Microapplication of CSF containing 0 mM HCO-3 (pH 4.80) effected significant increases in calibre of pial veins and arteries of 9.3 +/- 2.4% and 38.2 +/- 4% respectively (mean calibre change +/- SE), whereas CSF containing 22 mM HCO-3 (pH 7.45) which constricted pial arteries significantly (-18.5 +/- 2.9%) minimally altered venous calibre (-4.3 +/- 2.2%). Microapplication of CSF containing 0 mM potassium resulted in a significant reduction in pial arterial calibre (-11.4 +/- 2.8%) but failed to alter pial venous calibre (-0.3 +/- 0.6%). Perivascular microapplication of CSF containing moderately elevated potassium concentrations (10 mM) which effected marked, significant increases in pial arterial calibre (49.3 +/- 3.9%) did not significantly alter the calibre of the pial veins (mean response -1.6 +/- 2.4%). The perivascular administration of CSF containing a high concentration of potassium (40 mM) resulted in the significant constriction of both pial veins (-13.5 +/- 0.9%) and pial arteries (-47.2 +/-6.3%). The magnitude of the response was significantly smaller in the pial veins. The relative insensitivity to K+ and pH of the pial veins as compared to pial arteries suggests that alteration in the chemical composition of of the perivascular fluid are of lesser importance in the control of cerebrovascular capacitance than for the regulation of cerebrovascular resistance.

Animals↗
PubMed1982

Effects of nifedipine on potassium-induced contraction and noradrenaline release in cerebral and extracranial arteries from rabbit.

The present study was designed to evaluate the effects of the calcium antagonist nifedipine on potassium-evoked contractions and release of noradrenaline from sympathetic nerves in rabbit basilar and facial arteries. Contractions were measured isometrically in a small volume organ bath. While noradrenaline (NA) produced strong contractions in facial arteries, the majority of the basilar arteries responded only to the highest concentrations of NA employed (greater than 10 microM) with weak contraction. Prazosin (1 microM) and phentolamine (1-10 microM) effectively antagonized the responses to NA in both types of vessel. In contrast, contractions evoked by potassium (K+, 124 mM) were only slightly reduced by the alpha-adrenoceptor blocking agents, indicating that the participation of endogenous NA in maintaining the contractile response to K+ is either small or negligible in the vessel types studied. Nifedipine concentration-dependently inhibited K+-induced contractions in basilar and facial arteries, the former being significantly more affected as evidenced by the maximum inhibitions (approximately 80% compared to approximately 60%) and IC50 values (approximately 10 nM vs. approximately 30 nM). A combination of nifedipine (0.3 microM) and prazosin (1 microM) or phentolamine (1 microM) further suppressed the K+-evoked contractile response in facial arteries, but failed to do so in basilar arteries, when compared with the effect of nifedipine alone. The depressant effect of the alpha-adrenoceptor blockers was, however, still obtainable after reserpine treatment of the facial artery in vitro. Fluorescence histochemical demonstration of noradrenaline revealed a dense network of adrenergic nerve fibres in the walls of the basilar and facial artery. The vessels were also shown to accumulate 3H-NA and release it upon depolarization with K+. The uptake and subsequent release of 3H-NA were significantly reduced by desipramine (10 microM). Nifedipine (0.3-3.0 microM) failed to alter the K+-evoked 3H-NA efflux from sympathetic nerves in neither of the two vessel types. It may be concluded that nifedipine effectively inhibits K+-evoked contractions in isolated basilar and facial arteries from rabbit without interfering with nerve-mediated NA release. Possible explanations for this selective effect of nifedipine on muscle contraction are discussed.

Adrenergic Fibers↗
PubMed1982

Antagonism by (D-Pro2, D-Trp7,9)-substance P of the cerebrovascular dilatation induced by substance P.

The effects of (D-Pro2, D-Trp7,9)-substance P, a structural analogue of substance P, were examined in two models on cerebrovascular responses to substance P(SP) in cats; in vitro using segments of the middle cerebral artery and in situ by microapplication of the peptides close to pial arterioles. (D-Pro2, D-Trp7,9)-SP in concentrations up to 6.6 x 10(-6) M was without significant effect upon isolated middle cerebral arteries under normal conditions and in arteries contracted with prostaglandin F2 alpha. SP caused concentration-dependent relaxations of middle cerebral arteries contracted by prostaglandin F2 alpha (mean +/- SE; EC50: 2.0 +/- 1.6 x 10(-9) M). The presence of (D-Pro2, D-Trp7,9)-SP shifted the concentration-response curve of SP towards higher concentrations without significantly effecting the maximum response of the arteries to SP. A relaxation by 24.2 +/- 4.0% (n = 6) was obtained in prostaglandin F2 alpha contracted arteries by increasing the potassium concentration with 2 mM in the buffer solution. This response to potassium was unaltered in the presence of 6.6 x 10(-6)M of (D-Pro2, D-Trp7,9)-SP (25.0 +/- 7.1%, n = 5). Perivascular microapplication of SP around individual pial arterioles in situ effected dose-dependent increases in vascular calibre (mean response 14.5 +/- 2% with SP, 10(-7)M). The concomitant perivascular administration of (D-Pro2, D-Trp7,9)-SP (6.6 x 10(-6)M), which alone did not alter the arteriolar calibre, attenuated significantly the cerebrovascular response to SP (mean response 1.5 +/- 3.2%). On the basis of the agonist-antagonist relation found, these observations point to the possibility of a specific SP receptor site in cerebral arteries and arterioles.

Animals↗
PubMed1982

Feline cerebral veins and arteries: comparison of autonomic innervation and vasomotor responses.

1. The innervation of feline cerebral (pial) vessels by nerve fibres containing noradrenaline, substance P or vasoactive intestinal polypeptide (VIP) has been examined using the Falck-Hillarp histo-fluorescence method and immunohistochemical techniques. Cerebral veins were shown to be innervated by nerve fibres containing noradrenaline, substance P or VIP. Nerve fibres containing noradrenaline were the most numerous, while fibres containing substance P were observed least frequently in both types of vessel. For each putative neurotransmitter, the density of the innervation of the cerebral veins was less than that of cerebral arteries.2. The vasomotor responses of individual pial arteries and veins on the convexity of the cerebral cortex to perivascular micro-injection of noradrenaline, substance P and VIP were examined in twenty-five cats anaesthetized with alpha-chloralose.3. The perivascular micro-application of noradrenaline resulted in pronounced dose-dependent reductions in the diameter of pial veins (maximum calibre reduction: 32+/-3% noradrenaline 10(-5) M) and arteries (22+/-3% noradrenaline 10(-5) M). Pial veins were more sensitive to noradrenaline than were pial arteries tested under similar conditions. The reductions in the diameter of cerebral veins and arteries resulting from the administration of noradrenaline could be attenuated by the concomitant micro-application of phentolamine (10(-6) M).4. The perivascular micro-application of substance P effected significant dose-dependent increases in the calibre of pial veins (maximum calibre increase: 16+/-4% substance P 10(-7) M) which were of a similar magnitude to those observed in pial arteries in response to this peptide (21+/-4% substance P 10(-6) M).5. The perivascular micro-application of VIP resulted in small increases in the calibre of pial veins (maximum calibre increase: 9+/-2% VIP 10(-8) M) which were proportionately smaller than those observed in pial arteries in response to this peptide (23+/-5% VIP 10(-7) M).

Animals↗
PubMed1982

Vascular autonomic nerves and corresponding receptors in brain vessels.

Cerebral blood vessels, arteries and veins, are invested with a dense plexus of perivascular nerve fibres containing noradrenaline, acetylcholine esterase vasoactive intestinal polypeptide (VIP), substance P and avain pancreatic polypeptide (APP). The majority of the noradrenaline and APP-containing fibres disappear within one week after sympathectomy, while the other nerve fibres remain. Pharmacological studies of feline pial arteries in vitro have shown the presence of alpha 2- and beta 1- adrenoreceptors mediating contraction and dilatation, respectively. Dilatation can also be obtained by acetylcholine activating muscarinic receptors and by VIP and substance P.

Acetylcholine↗
PubMed1981

Perivascular substance P: occurrence and distribution in mammalian pial vessels.

Nerve fibres containing immunoreactive substance P (SP) were demonstrated in the wall of cerebral blood vessels of several mammalian species. Pial arteries of cat and guinea-pig were richly supplied with SP nerve fibres, while those of rat, rabbit, pig, and man had a moderate number. SP fibres were more numerous in pial vessels belonging to the rostral parts of the circle of Willis as compared to more caudally located blood vessels. In cat and guinea-pig, blood vessels in the choroid plexus were surrounded by few SP nerve fibres; also spinal cord blood vessels of cat contained few such fibres.

Animals↗
PubMed1981

Effects of extracellular calcium and of calcium antagonists on the contractile responses of isolated human pial and mesenteric arteries.

In isolated human pial arteries (diameter 0.4-0.5 mm), contractions were produced by potassium, noradrenaline, serotonin, and prostaglandin F2 alpha. For comparison, experiments were also performed on human mesenteric arteries. Threshold concentration for potassium-induced contraction in pial arteries was about 10 mM; in mesenteric arteries it was 3-5 mM higher. In pial arteries the calcium antagonists nifedipine and nimodipine caused an almost complete relaxation of contractions induced by potassium at drug concentrations relaxing prostaglandin F2 alpha-contracted vessels to only about 60%. Both nifedipine and nimodipine effectively inhibited contraction elicited by noradrenaline and serotonin in pial arteries. Nifedipine had a higher potency for relaxing cerebral than mesenteric arteries contracted by potassium (p less than 0.001). No such difference was demonstrated for nimodipine. In pial arteries pretreated in a calcium-free medium for 30 min, potassium depolarisation elicited contractions reaching a maximum amplitude of about 40% of that evoked in normal Krebs solution. Both nifedipine and nimodipine effectively inhibited contractions induced by calcium in pial arteries pretreated in a calcium-free medium and depolarised by potassium. The results suggest that potassium, amines, and prostaglandin F2 alpha activate isolated pial and mesenteric arteries by different calcium-dependent mechanisms and confirm the potent relaxant effects of nifedipine and nimodipine in these vessels.

Calcium↗
PubMed1981

Effects of pentobarbital on contractile responses of feline cerebral arteries.

The effects of pentobarbital on the contractile responses of isolated feline middle cerebral arteries have been examined. In the presence of pentobarbital (3 x 10(-4)M), the maximum contractions effected by potassium, noradrenaline, and prostaglandin F2 alpha were reduced by 37 +/- 3, 69 +/- 3, and 10 +/- 6%, respectively. The results caution against the use of pentobarbital as an anaesthetic agent in investigations of cerebrovascular reactivity.

Animals↗
PubMed1981

Adrenergic, cholinergic and peptidergic nerve fibres in dura mater--involvement in headache?

Nerve fibres containing noradrenaline, acetylcholinesterase, vasoactive intestinal polypeptide and substance P were demonstrated in the dura mater of guinea-pigs using histochemical and immunohistochemical methods. These fibres accompanied blood vessels of all size, indicating a vasomotor role. In addition, some nerve fibres were observed without any obvious relation to the blood vessels. The rich supply of nerve fibres to the various parts of the dura mater may possibly be of importance in the pathogenesis of some types of headache.

Acetylcholinesterase↗
PubMed1981

Action of 4-aminopyridine on the cerebral circulation.

4-Aminopyridine (4-AP) facilitates both inhibitory and excitatory synaptic activity in the central nervous system, and may, therefore, be a drug of potential therapeutic use in brain diseases with a disturbed synaptic transmission. In the present study the vasomotor effects upon isolated feline brain vessels, and regional cerebral blood flow and brain cortical metabolism in rats were examined. At high concentrations (above 10-6 M) a minor vasoconstriction was obtained of isolated pial vessels. Measurements of regional cerebral blood flow using the 14C-ethanol technique resulted in a significant increase in blood flow of caudate nucleus (93%), thalamus (74%) and cerebellum (82%). The arteriovenous oxygen difference of cortical tissue was reduced from 3.20 mmol O2/ml to 1.69 mmol O2/ml by 4-AP. This was not associated with an increase in cortical blood flow. Calculation of the cortical metabolic rate of oxygen, however, failed to demonstrate any significant change.

Aminopyridines↗