Search PubMed⌕ Search

Biomedical subjects

L Edvinsson

Publications and source records attributed to L Edvinsson.

At least 379 records · Page 21Linked to original sources
PubMed1984

Indoleaminergic mechanisms in brain vessels; localization, concentration, uptake and in vitro responses of 5-hydroxytryptamine.

Immunocytochemical studies have revealed the presence of 5-HT-containing nerve fibres in all parts of the cerebrovascular bed (arteries, arterioles and veins) of mouse, rat, guinea-pig, rabbit and cat. Biochemical measurements (using HPLC) revealed substantial concentrations of 5-HT and 5-HIAA in the pial vessels of the rat, rabbit, cat and man, the amounts corresponding well with the density of the perivascular nerve supply. The uptake of 3H-5-HT was studied in arteries removed from the circle of Willis in rats. Maximum uptake was reached after 15 min of incubation at 37 degrees C and plateaued at 30 min. The reaction was temperature-dependent and found to be absent if performed at 0 degrees C. Pharmacological experiments on isolated middle cerebral and basilar arteries showed that vessels from rat and dog were contracted by approximately 90% upon administration of 5-HT, whereas vessels from guinea-pig, rabbit, cat and man were contracted by 40 to 60% relative to 124 mM K+. The EC50 values in the different species varied by between 1.5 X 10(-7) M (rat) and 3 X 10(-9) M (dog). The 5-HT-induced contractions were blocked by the 5-HT antagonists, methysergide, methergoline and ketanserin. Transmural nerve stimulation (TNS) of the rabbit basilar artery revealed a tetrodotoxin sensitive constriction whereas TNS of cat and dog middle cerebral arteries caused a tetrodotoxin-sensitive relaxation. The relaxation was not significantly attenuated until high doses of methergoline (3 X 10(-6) M) or ketanserin (3 X 10(-5) M) had been given.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Neuropeptide Y: immunocytochemical localization to and effect upon feline pial arteries and veins in vitro and in situ.

Plexuses of nerve fibres containing neuropeptide Y (NPY)-like immunoreactivity invest pial arteries belonging to the circle of Willis, pial arterioles, occasionally penetrating arterioles and large veins. A more sparse supply of NPY-like fibres were observed around pial veins and venules. The NPY-immunoreactive fibres are located within the adventitia or at the adventitia-media border. Only occasional fibres are present in cerebral vessels of animals in which the superior cervical ganglion has been removed one week previously. Administration of NPY resulted in strong, concentration-dependent contractions of isolated feline middle cerebral arteries whereas administration of avian pancreatic polypeptide (APP) elicited weak contractions. In chloraloseanaesthetized cats, perivascular microapplication of NPY in situ resulted in marked concentration-dependent contractions of cerebral pial arterioles (34.7 +/- 6.6%; maximum decrease in calibre with NPY. Perivascular administration of NPY resulted in the constriction of pial veins but the magnitude of the venous calibre reductions was smaller than the response of arterioles at each reductions was smaller than the response of arterioles at each concentration examined. APP did not elicit contraction of pial arterioles or veins during in situ conditions. The pharmacological and immunocytochemical results strongly indicate the existence of a novel perivascular neuronal system containing NPY, which mediates contraction of cerebral blood vessels and NPY is colocalized with NA in sympathetic nerves.

Animals↗
PubMed1983

Neuropeptide Y: cerebrovascular innervation and vasomotor effects in the cat.

Avian pancreatic polypeptide (APP) has been proposed to be a neurotransmitter in a subpopulation of sympathetic nerves. Here, we present immunocytochemical and pharmacological evidence that the structurally related peptide, neuropeptide Y (NPY), is likely to be the biologically active material in these nerves. Cerebral arteries from cats are invested with a dense network of NPY-containing nerve fibres, as demonstrated by immunocytochemistry. This immunoreaction is abolished by prior removal of the superior cervical ganglion. NPY causes strong contractions of cerebral arteries in vitro whereas APP has small effects on the vasomotor reactivity. The NPY-induced contractions were not inhibited by the alpha 2-adrenoceptor antagonist rauwolscine (10(-7) M) or the 5-hydroxytryptamine antagonist ketanserin (10(-7) M). The contractions were, however, sensitive to calcium removal or to the calcium antagonist diltiazem (10(-4) M).

Animals↗
PubMed1983

Substance P: localization, concentration and release in cerebral arteries, choroid plexus and dura mater.

Substance P-like immunoreactivity (SPLI) was studied by immunocytochemistry and radioimmunoassay in the cerebral arteries, choroid plexus and dura mater of the guinea-pig, rabbit, cat and man. The highest concentrations were found in cerebral blood vessels: 6.1 +/- 2.3 pmol/g (guinea-pig), 9.0 +/- 1.1 pmol/g (rabbit), 7.1 +/- 0.4 pmol/g (cat), and 2.4 +/- 0.9 pmol/g (man). Lower levels were obtained in the choroid plexus and dura mater. The distribution of substance P (SP)-immunoreactive nerve fibres found in various regions of the guinea-pig correlated well with the amount of SPLI measured. Sympathectomy did not alter the concentration of SPLI in the dura mater or in cerebral blood vessels. Electrical field stimulation or 124 mM potassium enhanced the spontaneous efflux of SPLI by 10 and 20%, respectively, from superfused pial arteries in vitro. These data are in support of a functional role of perivascular SP within the cranial circulation.

Animals↗
PubMed1983

Analysis of vasospasm in hand arteries by in vitro pharmacology, hand angiography and finger plethysmography.

1. The distribution of sympathetic nerves in hand arteries and veins from 18 normal subjects was studied by microscopy according to the Falck-Hillarp histofluorescence method for the cellular visualization of cathecholamines and by quantitative analysis of noradrenaline with a radioenzymatic method. Segments of hand arteries and veins were tested in vitro for the vasomotor effect of sympathomimetic agonists. 2. Fluorescence microscopy revealed a plexus of noradrenaline-containing nerve fibres surrounding both arteries and veins. The concentration of noradrenaline in the walls were 4.5-4.7 ng/mg protein. The relative agonist potency was characteristic for alpha-receptors. Phentolamine produced parallel shift of the dose-response curves both for arteries and veins. 3. Finger plethysmography with local cold provocation down to 10 degrees C was performed in the patients with traumatic vasospastic disease before and after inhibition of the sympathetic nervous system by body warming and orally administered alcohol. Four patients had undisturbed circulation, as revealed by the ratio between the systolic blood pressure in the arm and in the finger in conjunction with cold provocation tests. 13 patients had vasospasm of varying degrees, and 3 patients suffered from organic stenosis. 4. Hand angiography was performed before and after local cold provocation. The patients with organic stenosis did not show vasodilatation after 4-6 mg phentolamine injection. Patients with true vasospasm responded, in addition, with efficient vasodilatation 15 min after reserpine injection, which also abolished the cold-induced vasospasm.

Angiography↗
PubMed1983

Cerebral veins: fluorescence histochemistry, electron microscopy, and in vitro reactivity.

Pial veins, choroid plexus veins, and the cerebri magna vein were investigated with regard to their ultrastructural organization, adrenergic nerve supply, and in vitro reactivity. The vessel walls consisted of a continuous layer of endothelial cells, large amounts of collagenous material, and occasional pericytes. Smooth muscle cells were observed only in a few specimens from the cerebri magna vein. All veins were surrounded by adrenergic nerve fibres. Potassium (124 mM) and noradrenaline (10(-5) - 10(-4) M) induced small contractions (0.2-0.5 mN) of isolated veins during in vitro conditions. The magnitude of these responses was less than one-tenth of that obtained in small pial arteries.

Animals↗
PubMed1983

Effects of bradykinin on pial arteries and arterioles in vitro and in situ.

The effect of bradykinin on cerebrovascular resistance vessels was investigated by the use of in vitro and in situ preparations. Bradykinin, in the range of 10(-10) to 10(-5) M, elicited a concentration-dependent vasodilatation on both feline and human pial arteries in vitro; the half-maximal response was found to be approximately at 2.8 X 10(-7) M and 1.3 X 10(-8) M (EC50), respectively. This dilatatory effect of bradykinin in vitro was found only in arteries preconstricted with prostaglandin F2 alpha or 5-hydroxytryptamine. In order to determine the effects of bradykinin on the diameter of cat pial arteries in situ, perivascular microapplication was employed. The dose-response curves obtained showed vasodilatation; the EC50 and the maximal response (EAm) were 4.4 X 10(-7) M and 45.5% at 10(-5) M, respectively. Statistically significant (p less than 0.01) reactions were observed at 10(-7) M and higher concentrations of bradykinin. The observed effects were independent of initial vessel size (80-260 microns). These in situ findings are very similar to those found in vitro. The isolated guinea pig ileum was used to check the stability of the bradykinin solutions. In this instance, a concentration-dependent contraction was found when "freshly prepared" or "5 hours stored" bradykinin was applied, indicating no measureable degradation of bradykinin. We conclude that bradykinin is a powerful vasodilator of both human and feline pial arteries.

Animals↗
PubMed1983

Responses of isolated feline and human cerebral arteries to prostacyclin and some of its metabolites.

The effects of prostacyclin (PGI2) were studied in isolated cat basilar and middle cerebral arteries and in human pial arteries. In feline vessels with low resting tension, PGI2 had a contractile effect that reached a maximum of 132% (basilar artery) and 23% (middle cerebral artery) of the potassium-induced (127 mM) contraction. In potassium-contracted feline vessels, PGI2 caused a further contraction. When these vessels were contracted by PGF2 alpha, PGI2 induced relaxation, which was most marked in the middle cerebral artery. PGI2 consistently relaxed the middle cerebral artery contracted by the prostaglandin endoperoxide analogue U-44069, whereas the basilar artery was almost unaffected. In human pial arteries with low resting tension, PGI2 had no effects in concentrations below 10(-6) M, whereas higher concentrations induced contractions. In potassium-contracted (35 or 127 mM) preparations, PGI2 in concentrations below 10(-6) M produced relaxation; in higher concentrations further contraction was induced. Human pial arteries contracted by PGF2 alpha, U-44069, noradrenaline, or 5-hydroxytryptamine consistently relaxed in response to PGI2 (less than 10(-6) M). The PGI2 metabolite 6-keto-PGE1 had effects similar to those of PGI2, but proved to be less potent on human pial vessels. 6-Keto-PGF1 alpha was ineffective, whereas 6,15-diketo-PGF1 alpha had minor relaxant effects. The results suggest that consideration must be given to regional as well as species differences concerning the cerebrovascular effects of PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Effects of topical application of a calcium antagonist (nifedipine) on feline cortical pial microvasculature under normal conditions and in focal ischemia.

Cat cortical arterioles and venules were exposed in vivo to the Ca2+ antagonist nifedipine under normal conditions and in focal ischemia. Topical application of nifedipine caused a marked, concentration-dependent arteriolar dilatation. The dilatatory responses increased significantly with decreasing arteriolar size. Perivenular microapplication of nifedipine invariably caused dilatation that was less pronounced but more long-lasting than that on the arteriolar side. Arterioles, which constricted after middle cerebral artery occlusion, invariably dilated following nifedipine application. These dilatatory responses were transient but could be repeated, and on some occasions were accompanied by a return of flow in vessels in which stasis had been present. The results suggest that nifedipine is able to dilate cerebral vessels both under normal conditions and when contracted during focal ischemia.

Animals↗
PubMed1983

Nerve fibres containing gastrin-releasing peptide around pial vessels.

Nerve fibres containing immunoreactive gastrin-releasing peptide (GRP) were demonstrated around pial blood vessels of cat, guinea pig, rat, and mouse. A sparse supply was found around spinal cord blood vessels, whereas the choroid plexus seemed to be devoid of GRP fibres. Sympathectomy did not affect the number or distribution of the GRP fibres. The administration of neither GRP nor its closely related analogue, bombesin, contracted or dilated feline pial arteries in vitro.

Animals↗
PubMed1983

Presence of alpha-adrenoceptors in human temporal arteries. Comparison between migraine patients and controls.

Alpha-adrenergic mechanisms have frequently been implied in migraine pathophysiology. We have examined the noradrenaline reactivity of isolated human temporal arteries removed from six migraine sufferers (not during attack) and from six patients without migraine operated for intracranial disorders. Noradrenaline constricted these vessels in a concentration-dependent manner, the response being altered by phentolamine 10(-8) M to 10(-6) M. There was no statistically significant difference between migraine patients and controls with respect to maximal contractile force (Emax) or pD2 (negative logarithm of the concentration eliciting half maximal force). The pA2 value for phentolamine was 8.3 in vessels from controls and 7.6 in arteries from migraine sufferers. The small difference between migraine patients and controls was not statistically significant. We obtained clear evidence of alpha-adrenergic receptors in human temporal arteries but their sensitivity was independent of the migraine disorder.

Adolescent↗
PubMed1983

Functional role for vasoactive intestinal polypeptide in the caudate nucleus: a 2-deoxy[14C]glucose investigation.

The quantitative autoradiographic 2-deoxy-[14C]glucose technique has been used with conscious rats to investigate the functional consequences (reflected as alterations in local rates of glucose utilization) of unilateral intrastriatal administration of vasoactive intestinal polypeptide. Intrastriatal administration of vasoactive intestinal polypeptide (20 pmol) significantly increased local glucose utilization in the injected striatum, where the increased use was localized in small punctate areas (100-500 microns wide in coronal sections) scattered throughout the nucleus at considerable distances (up to 4 mm) from the injection site. Significantly increased glucose utilization after intrastriatal injection of vasoactive intestinal polypeptide was observed in a number of regions (e.g., substantia nigra pars compacta, entopeduncular nucleus, lateral habenular nucleus, entorhinal, pyriform cortices, and amygdala) with known primary or secondary neuronal connections with the caudate nucleus. These alterations in glucose utilization were highly focal in nature, with the majority (40 of the 50 examined) of brain regions displaying unaltered rates of glucose utilization. The data provide evidence, obtained in conscious animals, that vasoactive intestinal polypeptide can modify functional processes in the caudate nucleus.

Animals↗
PubMed1983

Characterization of adenosine receptors in isolated cerebral arteries of cat.

The effect of some adenosine analogues and xanthine derivatives were studied on isolated cerebral arteries from cats. The adenosine analogues caused an almost complete relaxation of cerebral arteries contracted by prostaglandin F2 alpha (PGF2 alpha, 30 microM). The order of potency was: 5-N-ethylcarboxamide adenosine (NECA) greater than 2-chloroadenosine greater than adenosine greater than L-N6-phenylisopropyl adenosine (L-PIA). The analogue D-PIA was very weak and its maximum effect was small. NECA and L-PIA enhanced [3H]-cyclic AMP accumulation in [3H]-adenine labelled feline pial vessels with similar absolute and relative potency to their relaxant effects. The relaxant effects of adenosine and of NECA were competitively antagonized by 8-phenyl-theophylline (pA2 = 6.5). The effect of theophylline and enprofylline could not be tested in higher concentrations than 30 or 10 microM because they affected the vessels directly. At these concentrations they were essentially inactive as adenosine antagonists. The non-xanthine phosphodiesterase inhibitor rolipram (0.1 and 100 microM) caused a slight but non-significant potentiation of the relaxant effect of adenosine. The results are compatible with the opinion that adenosine relaxes cerebral vessels by an action on adenosine A2-receptors. The effect may be linked to adenylate cyclase and can be antagonized by 8-phenyl-theophylline.

Adenosine↗
PubMed1983

Influence of extracellular calcium and calcium antagonists on contractions induced by potassium and prostaglandin F2 alpha in isolated cerebral and mesenteric arteries of the cat.

1 The effects of a number of calcium antagonists (diltiazem, nifedipine, nimodipine and verapamil) have been studied on feline isolated pial arteries contracted by potassium (127 mM) or prostaglandin F2 alpha (PGF2 alpha, 2.5 microM) and mesenteric arteries contracted by potassium (127 mM). 2 Withdrawal of Ca2+ from the extracellular medium for 30 min reduced the contractile response to potassium in cerebral vessels by 92% and in mesenteric vessels by 96%. Subsequent addition of Ca2+ caused reproducible contractions which were inhibited by both nifedipine and nimodipine. 3 The four calcium antagonists relaxed the isolated middle cerebral artery contracted either by potassium or PGF2 alpha, and mesenteric arteries contracted by potassium, in the following order of potency: nimodipine greater than nifedipine greater than verapamil greater than diltiazem. 4 Nimodipine was more potent than nifedipine in cerebral arteries, and more potent in cerebral than in mesenteric arteries. Otherwise, the potassium-contracted cerebral and mesenteric vessels showed no major differences in sensitivity to calcium antagonists.

Animals↗
PubMed1983

Calcium antagonists: effects on cerebral blood flow and blood-brain barrier permeability in the rat.

1 Because they affect isolated cerebral arteries, some calcium antagonists have been studied on the intact cerebral circulation of the rat.2 Global cerebral blood flow ((133)Xe clearance technique) was measured in anaesthetized rats. Neither perhexiline (0.1 mug/kg to 1.0 mg/kg, i.v.) nor diltiazem (0.06-0.6 mg/kg, i.v.) had any significant effect on resting cerebral blood flow when measured 5 min after each dose. A high dose of nifedipine (1.0 mg/kg, i.v.) was administered during induced hypocapnia. Nifedipine failed to modify the hypocapnic vasoconstriction of the cerebral vasculature when compared to vehicle-treated rats.3 The possibility of discrete changes in regional cerebral blood flow was investigated. Local cerebral blood flow was measured in a number of brain regions by the [(14)C]-ethanol technique 15 min after the administration of nifedipine (20 or 100 mug/kg, i.v.). Nifedipine had no apparent effect on regional blood flow in the rat brain.4 Acute arterial hypertension increases protein leakage into the brain, a phenomenon susceptible to drugs that act on endothelial pinocytosis which is known to be calcium-dependent. The increase in protein extravasation, induced by the intravenous administration of either angiotensin II or adrenaline, was unchanged in rats previously treated with either nimodipine (20 mug/kg, i.v.) or nifedipine (50 mug/kg, i.v.) when dissolved in ethanol alone. However, nifedipine (20 mug/kg, i.v.) when dissolved in a solution of polyethylene glycol and ethanol further enhanced the hypertension-induced increase in brain albumin permeability.5 In conclusion, we have been unable to demonstrate any apparent effects of various calcium antagonists on the intact cerebral circulation of the rat, despite the number of different experimental models used.

Animals↗
PubMed1983

The feline carotid rete: vasomotor reactivity of isolated arteries.

Vasomotor responses of arteries from the feline carotid rete were examined using a sensitive in vitro system. The vessel segments constricted in response to several vasoactive agents and putative neurotransmitters. Sympathomimetic agents (noradrenaline, adrenaline, oxymetazoline, phenylephrine), 5-hydroxytryptamine, histamine, angiotensin II, and prostaglandin F2 alpha all induced concentration-dependent contractile responses. The contractions induced by noradrenaline, 5-hydroxytryptamine, and histamine could be antagonized by phentolamine, methysergide, and mepyramine, respectively. Cholinomimetics (acetylcholine, carbacholine), vasoactive intestinal peptide and papaverine induced potent dilatory responses. The effect of carbacholine was shifted towards higher agonist concentrations by atropine. Dilatations, though small in magnitude, were found by application of adenosine, isoproterenol, and histamine. These results correlate well with the recent demonstration of autonomic nerves and indicate the occurrence of corresponding receptor sites in the walls of the carotid rete arteries.

Acetylcholine↗