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Biomedical subjects

L Edvinsson

Publications and source records attributed to L Edvinsson.

At least 325 records · Page 18Linked to original sources
PubMed1988

Enhanced vasoconstrictor responses to potassium, 5-hydroxytryptamine, and prostaglandin F2 alpha of isolated coronary arteries from magnesium-deficient rats. Comparison with vasomotor activity of aorta.

Wistar rats were fed a low magnesium diet for 8 or 12 weeks, resulting in reduced levels of magnesium in plasma, heart, and skeletal muscle, as compared with pair-fed control rats. The magnesium-deficient rats also had reduced tissue levels of potassium. Coronary arteries and thoracic aorta from magnesium-deficient rats and control rats were incubated in tissue baths and the contractile responses to potassium, 5-hydroxy-tryptamine, and prostaglandin F2 alpha were investigated using a sensitive in vitro system. The concentration-contraction curve, for all agents was shifted to the left in coronary arteries from magnesium-deficient rats. In aorta from magnesium-deficient rats, the pattern of change in reactivity to these agonists was not uniform: the concentration-contraction curve for 5-hydroxytryptamine was shifted to the left, the contractile response to prostaglandin F2 alpha was reduced, while there was no change in the response to potassium. The contractile response to the administration of calcium to calcium-depleted, potassium-depolarized vessels from magnesium-deficient rats was enhanced; the effect was more pronounced in coronary arteries as compared to the aorta. Hence, the vasomotor reactivity of coronary arteries appears to be more sensitive than is the aorta during magnesium-deficient conditions.

Animals↗
PubMed1988

Heterogeneous vasomotor responses of anatomically distinct feline cerebral arteries.

1. The vasomotor reactivity to a number of neurotransmitters and blood-borne substances was evaluated in several anatomically distinct arteries of the cat cerebral circulation. Few regional differences were observed in their vasoconstrictor responses to noradrenaline, dopamine, 5-hydroxytryptamine and prostaglandin F2 alpha. Only the anterior cerebral artery reacted strongly to all vasoconstrictor agents. 2. Adenosine, acetylcholine and histamine induced pronounced relaxation in the vast majority of the major cerebral arteries. The relaxation elicited by adenosine showed a slight degree of heterogeneity between the arteries and the overall response accounted for 81 +/- 6% of the pharmacologically-induced tone. On the other hand, the dilatation induced by acetylcholine and histamine varied as a function of the anatomical localization of the cerebral arteries. The acetylcholine-induced vasodilatation was significantly more pronounced in the middle cerebral, anterior communicating and anterior cerebellar arteries, with respective responses of 72, 66 and 83% of the induced tone as compared to 43% in the other vessels. However, all arteries were equally sensitive to acetylcholine with an overall mean pD2 value of 7.47 +/- 0.06. The most heterogeneous results were obtained with histamine and applied both to the magnitude of the maximal response and the sensitivity of the various arteries to this amine. The intensity of the relaxation varied from 20% (anterior communicating artery) to 118% (posterior cerebellar artery). 3. Among the neuropeptides studied, substance P and bradykinin were considerably less potent than vasoactive intestinal peptide on all the cerebral arteries. The least responsive vessel to bradykinin was the anterior cerebral artery with a maximal response of 22 +/- 5% of the induced-tone and a pD2 value of 7.56 +/- 0.24. All vessels responded weakly to substance P and those from the vertebrobasilar circulation were significantly less sensitive to this neuropeptide with pD2 values around 8.07 as compared to 9.82 in the more rostral arteries. Although all vessels were equally sensitive to vasoactive intestinal peptide, the dilator responses were significantly less pronounced in the middle cerebral and basilar arteries (maximal response of 86 +/- 5% and 69 +/- 6% of the induced-tone, respectively, as compared to 110 +/- 9% in the other vessels). 4. The vertebrobasilar arteries were as reactive, if not more reactive, to vasoconstrictors than the vessels originating from the carotid circulation. In contrast, the dilator responses were less marked in most caudal arteries. Such dichotomies may be important in the regulation of local cerebral blood flow. 5. The results emphasize the considerable heterogeneity in the vasomotor responses to a given substance among the various cerebral arteries. Further, they suggest the presence of multiple receptor populations which mediate opposite effects and which are distributed in different proportions among the cephalic arteries.

Animals↗
PubMed1988

Characterization of histamine receptors in isolated human cerebral arteries.

1. The subtypes of histamine-receptors which mediate dilatation of small human cerebral arteries have been characterized in vitro using 'selective' agonists and antagonists. 2. Dilator responses were studied after preconstriction with prostaglandin F2 alpha, since contraction was not seen with histamine concentrations up to 10(-4) M. Histamine caused a concentration-related relaxation of cerebral vessels with an IC50 value of 5.2 +/- 1.6 x 10(-8) M. 3. Mepyramine caused a parallel shift to the right of the histamine concentration-response curve whereas cimetidine was without observable effect. This suggests the presence of histamine H1-receptors only. However, combined treatment with mepyramine and cimetidine caused a more marked displacement of the concentration-response curve to the right. Schild analysis indicated that in situations of near complete blockade of either of the histamine receptor subtypes, simple competitive antagonism both at H1- and H2-receptors can be revealed with a pA2 value of 8.64 for mepyramine and a pA2 value of 6.52 for cimetidine. 4. The 'selective' H1-receptor agonists pyridylethylamine, 2-methylhistamine (2-Me-histamine) and thiazolylethylamine, and the H2-receptor agonists dimaprit, impromidine and 4-methylhistamine (4-Me-histamine) all mimicked the histamine response, but were less potent than histamine. The order of potency was thiazolylethylamine greater than dimaprit greater than impromidine greater than 2-Me-histamine greater than pyridylethylamine greater than 4-Me-histamine. 5. These results indicate that the histamine-induced dilatation in small human cerebral arteries is mediated by both H1- and H2-receptors and that the former subtype of histamine receptor predominates.

Adult↗
PubMed1988

Effect of pregnancy and sex steroids on alpha 1-adrenoceptor mechanisms in the guinea-pig uterine vascular bed.

Adrenoceptor mechanisms in the extrinsic uterine arteries from late pregnant guinea-pigs were characterized pharmacologically and compared with contractile responses of uterine arteries from non-pregnant and oophorectomized control, progesterone and oestrogen treated animals. Pregnancy caused an increase in diameter of the arteries, more pronounced the more distal they were. There was no change in potassium-evoked maximum contractions during pregnancy. Noradrenaline (10 nM to 1 mM), in the presence of cocaine (1 microM) and propranolol (0.1 microM), induced concentration-dependent contractions of the arterial segments, with approximately similar pD2 values. The maximum responses (Emax) were significantly increased during pregnancy and hormone supplementation. Prazosin (10 nM to 1 microM), but not rauwolscine (10 nM to 1 microM), antagonized noradrenaline-evoked contractions of the arteries. Isoprenaline (10 nM to 1 microM), in the presence of prazosin (0.1 microM) and cocaine (1 microM), had no relaxant effect on arteries contracted submaximally by prostaglandin F2a (5 microM). Neither cocaine nor normetanephrine modified noradrenaline-evoked contractions of the uterine artery. The results indicate that guinea-pig uterine vasoconstriction is mediated by alpha 1-adrenoceptors while relaxant beta-adrenoceptor effects, neuronal and extraneuronal uptake mechanisms are of minor importance. The observed increase in Emax may be due either to an increase in the number of alpha 1-adrenoceptors or to an enhanced pharmaco-mechanical coupling, which conceivably is regulated by sex steroids since this response was reproduced in castrated animals by hormone supplementation.

Animals↗
PubMed1988

The influence of magnesium on the release of calcium from intracellular depots in vascular smooth muscle cells.

Vasoconstrictor responses to prostaglandin F2 alpha and noradrenaline were investigated in ring segments of feline femoral, coronary and cerebral arteries incubated in calcium-free solutions containing different concentrations of magnesium (1.2, 4.4 and 13.2 mM). Contractions produced by prostaglandin F2 alpha and noradrenaline were depressed when calcium was omitted from the incubation solution. The presence of raised concentrations of magnesium (4.4 or 13.2 mM) in the tissue bath further depressed the prostaglandin F2 alpha and noradrenaline contractions in calcium-free medium. In a separate set of experiments the vessel wall contents of cAMP and cGMP were measured before and after the additions of 4.4 or 13.2 mM magnesium; stable relaxations by magnesium were noted but there was no parallel change in the vessel content of cAMP or cGMP. The results indicate that magnesium may interfere with the release of calcium from intracellular depots, and that neither adenylate cyclase, nor guanylate cyclase are involved in the dilator activity of magnesium in isolated arteries.

Animals↗
PubMed1988

Vasomotor changes in isolated coronary arteries from diabetic rats.

Contractile responses to prostaglandin F2 alpha, serotonin, noradrenaline, and potassium were examined in isolated intramyocardial arteries of Wistar rats 8 weeks after the induction of diabetes mellitus by administration of streptozotocin (STZ). The concentration-response curves obtained were compared with those noted in vessels both from age- and from weight-matched control rats. Light and electron microscopy did not reveal any major change in coronary artery wall thickness or morphology. There was no difference in the pattern of vasomotor responses between the two control groups. Contractile responses to prostaglandin F2 alpha, and potassium were significantly reduced, while contractile responses to serotonin and noradrenaline were unaltered in coronary arteries from diabetic rats. The vasomotor responses to noradrenaline and potassium showed a biphasic pattern in control vessels, i.e. contraction noted at high agonist concentrations was preceded by slight, but reproducible relaxation at lower concentrations. In diabetic vessels these relaxant responses were absent. The contraction produced by noradrenaline was markedly enhanced by the presence of propranolol in both diabetic and control vessels. Dilator responses to verapamil, diltiazem, nifedipine, papaverine and magnesium were studied in serotonin-precontracted coronary arteries; the concentration-response curves obtained by verapamil and diltiazem were shifted to the right in diabetic vessels. It appears justified to use vessels from age-matched rats as controls when vasomotor reactivity in coronary arteries from STZ-diabetic rats is investigated. The reduction in contractile responses to prostaglandin F2 alpha and potassium, and the reduction or lack of relaxant responses to noradrenaline, potassium, verapamil and diltiazem, in diabetic coronary arteries, indicate a selective modification of the coronary circulation by the diabetic disease.

Animals↗
PubMed1987

Neuronal versus endothelial origin of vasoactive acetylcholine in pial vessels.

Functional pial vessels denuded in situ of the endothelial cell layer exhibit a markedly decreased choline uptake capacity (-53%) but integrally preserved choline acetyltransferase (ChAT) activity and acetylcholine (ACh) release mechanisms. These studies demonstrate that endothelial cells possess a specific choline uptake system. However, the unimpaired ChAT activity in denuded pial vessels implies that the endothelial pool of choline is not significantly metabolized into ACh. In spite of possible differences in the mechanisms that govern release processes in endothelial and neuronal elements, taken together the findings of the present study suggest that the ACh released following depolarization of pial blood vessels originates predominantly from cholinergic perivascular nerve terminals.

Acetylcholine↗
PubMed1987

Peptide-containing nerve fibers in human cerebral arteries: immunocytochemistry, radioimmunoassay, and in vitro pharmacology.

Nerve fibers containing neuropeptide Y, vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) were seen in the adventitia or at the adventitia-media border of human cerebral arteries obtained during neurosurgical procedures. Radioimmunoassay of human cerebral arteries, removed at autopsy, revealed that the levels of the four peptides did not differ among the major cerebral arteries. There was, however, a gradual decline in peptide concentrations with increasing age of the patients, as measured in the proximal part of the middle cerebral artery. Pharmacological experiments on fresh segments of cerebral (pial) arteries in vitro revealed that neuropeptide Y caused vasoconstriction per se but did not potentiate the contractile response of noradrenaline. VIP, peptide histidine methionine-27 (PHM-27), SP, neurokinin A (NKA), and human CGRP potently relaxed vessels precontracted by prostaglandin F2 alpha, the relative potency being human CGRP greater than SP greater than VIP greater than NKA greater than PHM-27. The amount of relaxation varied between 55% (SP) and 96% (human CGRP) of the prostaglandin F2 alpha-induced contraction. The peptide effects were not antagonized by propranolol, atropine, or cimetidine, suggesting an action that does not involve adrenergic, cholinergic, or histaminergic receptors.

Age Factors↗
PubMed1987

The concept of coupling blood flow to brain function: revision required?

A tight coupling exists between brain function and cerebral perfusion in most situations. The Roy and Sherrington hypothesis has been widely accepted to account for the phenomenon: increased neuronal metabolic activity will give rise to the accumulation of vasoactive catabolites, which decrease vascular resistance and thereby increase blood flow until normal homeostasis is reestablished. However, the hypothesis does not account for the disproportionate increase in flow that occurs in a number of circumstances. There are additional difficulties in reconciling more recent experimental data with the Roy and Sherrington hypothesis. In this review we direct attention toward the rich perivascular nerve supply to all parts of the cerebral circulation as possibly being an alternative control system allowing for rapid parallel changes in flow and neuronal activity.

Animals↗
PubMed1987

Methylergometrine antagonizes 5 HT in the temporal artery.

Methylergometrine, the main metabolite of methysergide, has 40-times greater 5 HT antagonistic potency than methysergide in isolated segments of human temporal artery. It is suggested that methylergometrine is the "active" drug when methysergide is used in migraine prophylaxis, and that the two compounds should be compared in prophylactic trials in migraine.

Humans↗
PubMed1987

Perivascular innervation of the cerebral circulation: involvement in the pathophysiology of subarachnoid hemorrhage.

The authors describe the perivascular innervation of cerebral circulation. The different nerve fiber systems can be classified as follows: 1. Sympathetic (noradrenaline, neuropeptide Y), 2. Parasympathetic (acetylcholine, vasoactive intestinal peptide/peptide histidine isoleucine (methionine), 3. Sensory (tachykinins, calcitonin gene-related peptide). Each of these systems is outlined by their basic anatomical and physiological facts. Then, the etiology of cerebral vasospasm after subarachnoid hemorrhage is discussed in relation to the cerebrovascular innervation.

Animals↗
PubMed1987

Intravenous physostigmine treatment of Alzheimer's disease evaluated by psychometric testing, regional cerebral blood flow (rCBF) measurement, and EEG.

Ten patients with Alzheimer's disease were treated with intravenous infusion of physostigmine for 2 h. The acute effects on cognitive function, regional cerebral blood flow, and EEG were compared to placebo (isotonic glucose) using a double-blind cross-over design. Physostigmine causes a limited improvement of psychomotor performance and EEG and an increase of blood flow in the most severely affected cortical areas, predominantly in an early phase of Alzheimer's disease.

Aged↗
PubMed1987

Calcitonin gene-related peptide and cerebral blood vessels: distribution and vasomotor effects.

The innervation of cerebral blood vessels by nerve fibers containing calcitonin gene-related peptide (CGRP) and the vasomotor effects of this peptide are described for a number of different mammalian species. CGRP-immunoreactive nerve fibers were present in the adventitia of cerebral arteries in all species examined (guinea pig, cat, rabbit, rat, and mouse). Numerous perikarya containing CGRP immunoreactivity are demonstrable in the trigeminal ganglion of all species. In the cerebral perivascular nerve fibers and in trigeminal perikarya, CGRP is often colocalized with substance P and neurokinin A. Marked interspecies differences exist both in the density of CGRP-immunoreactive nerve fibers and in the cerebrovascular levels measured with radioimmunoassay. The highest concentrations were observed in cerebral vessels from guinea pigs, the lowest concentration in rabbit vessels, and intermediate levels in the feline and human cerebral vasculature. CGRP is a potent dilator of cerebral arteries in all species examined (human pial, feline middle cerebral, rabbit, guinea pig and rat basilar arteries). The concentration of CGRP eliciting half-maximal responses ranged from 0.4 nM (human pial artery) to 3 nM (rat and rabbit basilar arteries). Pretreatment of cerebral arteries with low concentrations of either substance P (0.1 nM) or neurokinin A (3 nM) attenuated slightly the CGRP-induced relaxations of guinea pig basilar arteries. Calcitonin was found to be a very weak dilator of cerebral arteries from human and guinea pig. Thus, cardiovascular nerve fibers containing CGRP appear to be present in all mammalian species (although to varying degrees) and CGRP is invariably a potent dilator of the cerebral arteries for all species.

Animals↗
PubMed1987

Nerve fibers containing neuropeptide Y in the cerebrovascular bed: immunocytochemistry, radioimmunoassay, and vasomotor effects.

Perivascular nerve fibers containing neuropeptide Y (NPY)-like immunoreactivity were identified around cerebral blood vessels of human, cat, guinea pig, rat, and mouse. The major cerebral arteries were invested by dense plexuses; veins, small arteries, and arterioles were accompanied by few fibers. Removal of the superior cervical ganglion resulted in a reduction of NPY-like material in pial vessels and dura mater. Pretreatment with 6-hydroxydopamine or reserpine reduced the number of visible NPY fibers and the concentration of NPY in rat cerebral vessels. Sequential immunostaining with antibodies toward dopamine-beta-hydroxylase (DBH) (an enzyme involved in the synthesis of noradrenaline) and NPY revealed an identical localization of DBH and NPY in nerve cell bodies in the superior cervical ganglion and in perivascular fibers of pial blood vessels, suggesting their coexistence. Administration of NPY in vitro resulted in concentration-dependent contractions that were not modified by a sympathectomy. The contractions induced by noradrenaline, 5-hydroxytryptamine, and prostaglandin F2 alpha and the dilator responses to calcitonin gene-related peptide were not modified by NPY in rat cerebral arteries. However, the constrictor response to NPY was reduced by 70% in the presence of the calcium entry blocker nifedipine, and abolished following incubation in a calcium-free buffer. These data suggest an interaction of NPY at a postsynaptic site, which for induction of contraction may open calcium channels in the sarcolemma of cerebral arteries.

Animals↗
PubMed1987

Concentrations of putative neurovascular transmitters in major cerebral arteries and small pial vessels of various species.

The levels of noradrenaline, neuropeptide Y, 5-hydroxytryptamine, and substance P were measured and compared between the large arteries of the circle of Willis and the small cerebral vessels of the pia mater in the rat, rabbit, cat, and monkey. In all species, noradrenaline and neuropeptide Y concentrations were greater in the larger arteries than in small pial vessels. Noradrenaline concentrations were dramatically reduced following cervical sympathectomy, with the extent of diminution differing greatly in the various species; the effects of cervical ganglionectomy on neuropeptide Y concentrations were less pronounced. 5-Hydroxytryptamine concentrations in rats, cats, and rabbits were significantly greater in the small pial vessels, although measurable concentrations existed in the circle of Willis. In cats and monkeys, substance P was found in major arteries, but was not detectable at the level of the small pial vessels. The differences in the regional distribution of the various neurotransmitter candidates in the cerebrovascular bed may reflect their physiological significance.

Animals↗