Search PubMed⌕ Search

Biomedical subjects

L Edvinsson

Publications and source records attributed to L Edvinsson.

At least 361 records · Page 20Linked to original sources
PubMed1986

Vasomotor effects of magnesium: a comparison with nifedipine and verapamil of in vitro reactivity in feline cerebral and peripheral arteries.

The vasomotor effects of magnesium ions and the calcium entry blockers nifedipine and verapamil have been studied in isolated feline cerebral, coronary and femoral arteries preconstricted by 124 mM potassium or 3 microM prostaglandin F2 alpha (PGF2 alpha). The order of potency for eliciting relaxation was: nifedipine greater than verapamil greater than magnesium. Magnesium showed the same profile of action as the calcium entry blockers in cerebral and coronary arteries, while the maximum relaxation obtained by magnesium was significantly smaller in femoral arteries constricted by potassium as compared with that of nifedipine (p less than 0.001) and verapamil (p less than 0.01). Besides this relaxant effect, magnesium was found to act as a constrictor during certain conditions; addition of magnesium to femoral arteries which had been preconstricted by PGF2 alpha in a magnesium-free solution resulted in relaxation in low concentrations and contraction at higher concentrations. In separate experiments, a raised extracellular concentration of magnesium was found to enhance the constrictor response to PGF2 alpha in femoral but not in coronary arteries. Cerebral arteries showed a pattern of reaction that was somewhat different from that observed in peripheral arteries. The level of maximum relaxation by magnesium in cerebral arteries was twice that found in peripheral arteries. Cerebral arteries were significantly more sensitive to verapamil than peripheral arteries.

Animals↗
PubMed1985

Innervation of the feline cerebral vasculature by nerve fibers containing calcitonin gene-related peptide: trigeminal origin and co-existence with substance P.

The presence of a population of nerve fibers containing immunoreactive calcitonin gene-related peptide (CGRP) has been demonstrated around cerebral arteries of the cat with immunocytochemistry and radioimmunoassay. CGRP immunoreactivity in the feline cerebral vasculature, as characterized by high-performance liquid chromatography, is similar to authentic rat CGRP. Numerous perikarya containing CGRP are present in the trigeminal ganglia, and surgical lesions of the trigeminal ganglia significantly reduce the levels of CGRP in the cerebral vasculature, suggesting that this cranial nerve is the principal origin of these cerebrovascular nerve fibers. As demonstrated by sequential immunocytochemistry, CGRP coexists with substance P both in the trigeminal ganglion and nerve fibers around cerebral blood vessels. The presence of CGRP in the cerebrovascular trigeminal innervation provides further versatility and complexity for this sensory afferent system putatively involved in the transmission of intracranial pain.

Animals↗
PubMed1985

Perivascular peptides relax cerebral arteries concomitant with stimulation of cyclic adenosine monophosphate accumulation or release of an endothelium-derived relaxing factor in the cat.

Calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal polypeptide (VIP) have been proposed to be neurotransmitters/neuromodulators in cerebral perivascular nerve fibers. Here, we present pharmacological and biochemical evidence showing that these peptides have different modes of relaxing cerebral blood vessels in the cat. CGRP causes pronounced relaxation, this occurs simultaneously with stimulation of cyclic adenosine monophosphate (cAMP) accumulation. The strong VIP-induced dilatation is parallelled by cAMP accumulation, albeit of a lower magnitude than with CGRP. The SP-induced relaxation was much weaker than that of CGRP and VIP, and it was not associated with cAMP accumulation. Only at concentrations of SP where maximum relaxation had occurred, was a nonsignificant cAMP accumulation seen. The responses to SP and acetylcholine were absent in arteries where the endothelium had been removed, whereas the relaxations induced by CGRP and VIP persisted.

Adenylyl Cyclases↗
PubMed1985

Neuropeptide Y-like immunoreactivity in perivascular nerve fibres of the guinea-pig.

The distribution of perivascular nerve fibres displaying neuropeptide Y-like immunoreactivity was studied in the guinea-pig. Generally, neuropeptide Y fibres were numerous around arteries and moderate in number around veins. In the heart, immunoreactive fibres were numerous in the auricles and the atria (epi- and endocardium) whereas the ventricles had a more scarce supply. The coronary vessels were richly supplied with fibres. Around large elastic and muscular arteries the fibres formed well developed plexuses. Small arteries in the respiratory tract, the gastrointestinal tract and the genito-urinary tract received a particularly rich supply. In the liver, spleen and kidney only few perivascular fibres were seen. Since immunoreactive fibres around blood vessels disappeared upon surgical or chemical sympathectomy, and sequential immunostaining with antisera against dopamine-beta-hydroxylase (a marker for adrenergic neurons) and against neuropeptide Y revealed their co-existence, it is concluded that neuropeptide Y fibres around blood vessels are sympathetic and adrenergic.

Animals↗
PubMed1985

Distribution and vasomotor effects of peptide HI (PHI) in feline cerebral blood vessels in vitro and in situ.

Peptide HI (PHI)-immunoreactive nerve fibres were numerous around cerebral blood vessels of the cat. The number and distribution resemble that previously found for vasoactive intestinal polypeptide (VIP), a peptide with which PHI co-exists in pial arteries, at least in some segments. PHI and VIP elicit dilatation in a concentration-dependent manner in isolated middle cerebral arteries; the maximum effects were similar but VIP was considerably more potent. Neither effect was blocked by atropine, cimetidine or propranolol, confirming an action at a non-adrenergic, non-cholinergic site. In chloralose-anaesthetized cats PHI and VIP elicited concentration-dependent dilatations; the magnitude of responses was similar, however, considerably more PHI was necessary to elicit the same response as that of VIP. The results suggest that though both peptides are co-localized and may act at the same receptor, VIP is a more likely candidate for eliciting dilatation during physiological conditions.

Animals↗
PubMed1985

Innervation of human omental arteries and veins and vasomotor response to noradrenaline, neuropeptide Y, substance P and vasoactive intestinal peptide.

Human omental arteries and veins are supplied with nerve fibers containing noradrenaline (NA) and neuropeptide Y (NPY); these two agents probably co-exist in perivascular sympathetic nerve fibers. Substance P (SP)- or vasoactive intestinal peptide (VIP)-containing fibers could not be detected. In studies on isolated omental vessels NA produced constriction. The results of blockade experiments suggest that human omental arteries are equipped predominantly with alpha 1-adrenoceptors and omental veins with a mixture of alpha 1- and alpha 2-adrenoceptors. NPY at a concentration of 10(-7) M or higher had a weak contractile effect on veins and virtually no effect on arteries. NPY at a concentration of 3 X 10(-8) M shifted the NA concentration response curve to the left in arteries (pD2 = 5.8 for NA versus 6.6. for NA in the presence of NPY; P less than 0.001) but not in veins. Both SP and VIP relaxed arteries precontracted with NA or prostaglandin F2 alpha (PGF2 alpha). The potency of SP as a relaxant agent was similar in arteries and veins; the effect of VIP was elicited at lower concentrations in veins than in arteries.

Aged↗
PubMed1985

Functional bases for a central serotonergic involvement in classic migraine: a speculative view.

The rôle of serotonin (5-HT) in the cerebrovascular bed is the subject of the following review. Cerebral blood vessels are supplied with 5-HT-containing fibres which originate in the raphé nuclei in the brainstem. The activation of this system may result in a constriction of large arteries and a dilatation of arterioles. Intra-arterial administration of 5-HT causes reduction in cerebral blood flow and metabolism provided it bypasses the blood-brain barrier. The findings, marked changes in plasma levels of 5-HT and in cerebral blood flow during a classic migraine attack, are suggestive of an involvement of the 5-HT system.

Animals↗
PubMed1985

Vasomotor responses of cerebral arterioles in situ to putative dopamine receptor agonists.

The vasomotor responses of individual cerebral pial arterioles on the convexity of the cerebral cortex to subarachnoid perivascular micro-injections of dopamine and the putative dopamine receptor agonists, apomorphine, SKF 38393 and LY 141865, have been examined in 38 anaesthetized cats. The perivascular microapplication of dopamine (10(-9)-10(-3)M) effected dose-dependent reductions in pial arteriolar calibre, with the maximum reductions in calibre (22 +/- 2% from preinjection levels: mean +/- s.e.) being observed at 10(-3)M. The cerebrovascular constriction produced by dopamine (10(-5)M) could be significantly attenuated by the concomitant perivascular administration of phentolamine (10(-6)M) or methysergide (10(-6)M). The perivascular microapplication of apomorphine (10(-8)-10(-4)M) effected dose-dependent increases in arteriolar calibre, with the maximum increase (31 +/- 6%) being observed with apomorphine (10(-5)M). The perivascular administration of the putative dopamine D1-receptor agonist, SKF 38393 (10(-9)-10(-4)M) increased arteriolar calibre, with the maximum response (24 +/- 3%) being observed with injection of 10(-7)M. The putative dopamine D2-receptor agonist, LY 141865, also increased cerebral arteriolar calibre, but only at high concentrations (maximum calibre increase 25 +/- 6.1 with 10(-4)M). The cerebrovascular dilatations elicited by apomorphine and by SKF 38393 were markedly attenuated by the concomitant perivascular microapplication of the putative dopamine D1-receptor antagonist, SCH 23390 (10(-8)M). The perivascular administration of SCH 23390 (10(-9)-10(-5)M) per se did not alter arteriolar calibre nor the arteriolar dilatation provoked by microinjections of acidic cerebrospinal fluid. These results point to the presence on cat cerebral arterioles of dopamine receptors (probably of D1 subtype) mediating dilation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1985

Cerebrovascular responses to haemorrhagic hypotension in anaesthetized cats. Effects of alpha-adrenoceptor antagonists.

Haemorrhagic hypotension induces the phenomenon of cerebrovascular autoregulation and, concomitantly, involves an activation of the sympathetic nervous system. As brain vessels in cats have an atypical adrenoceptor distribution we studied the effects of an alpha-adrenoceptor antagonist on the autoregulatory response to haemorrhage. Cortical blood flow was studied by the H2 technique in chloralose-anaesthetized cats subjected to a period of graded haemorrhage over 3 h. Three groups of cats were studied: control, i.e. those receiving saline (n = 10); yohimbine-treated (200 micrograms . kg-1 . h-1, n = 7); and prazosin-treated (50 micrograms . kg-1 . h-1, n = 6). In the control group, cortical blood flow remained relatively constant when mean arterial pressure was decreased from 102 +/- 1 mmHg (mean +/- SE) to approximately 50 +/- 1 mmHg; thereafter, blood flow decreased with decreasing perfusion pressure. In the arterial pressure range 64-55 mmHg, cortical blood flow was significantly higher in the yohimbine group (109 +/- 12 ml . 100 g-1 . min-1) compared to the control group (69 +/- 6 ml . min-1) and remained higher in the yohimbine-treated cats at more extreme levels of hypotension. Blood flow did not fall significantly in the yohimbine-treated cats until mean arterial pressures of 31 +/- 1 mmHg were attained. In the prazosin-treated cats, flow began to decrease at arterial pressures even greater than those observed in the control group. Thus, there is a sympathetic vasoconstriction of brain arteries that is primarily mediated by alpha 2-adrenoceptors in the feline cerebrovascular bed.

Anesthesia, General↗
PubMed1985

Characterization of the contractile effect of neuropeptide Y in feline cerebral arteries.

The action of neuropeptide Y (NPY), which coexists with noradrenaline (NA) in perivascular sympathetic nerves, has been examined on feline cerebrovascular smooth muscle using a sensitive in vitro system. The direct cerebrovascular responses of peptides with structural similarities with NPY, peptide YY (PYY), avian (APP), and bovine (BPP) and human (HPP) pancreatic polypeptides, have been compared with that of NPY on isolated feline cerebral arteries. The relative potency for contractions induced by the peptides is: NPY, PYY greater than APP greater than BPP, HPP. The alpha-adrenoceptor antagonist rauwolscine, which blocked the response to noradrenaline (NA), had no effect on NPY-induced contractions. Neuropeptide Y significantly potentiated contractions induced by 10(-6) M NA, but not by 10(-5) M. Withdrawal of Ca2+ from the extracellular medium for 30 min reduced the contractile response to NPY in cerebral vessels by about 80%. Subsequent readdition of Ca2+ caused reproducible contractions which were inhibited by the calcium entry blocker nimodipine. Nimodipine also relaxed isolated middle cerebral artery segments contracted by NPY and NA in a concentration-dependent manner. The data suggest that NPY mediates contraction of cerebrovascular smooth muscle via a mechanism that is dependent on the concentration of extracellular calcium.

Adrenergic alpha-Antagonists↗
PubMed1985

Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction: mode of action.

Neuropeptide Y (NPY), which co-exists with noradrenaline (NA) in postganglionic sympathetic nerves, was able to potentiate NA-evoked constriction in certain isolated rabbit blood vessels. The phenomenon was observed in the femoral, the gastroepiploic and the pulmonary arteries but not in the femoral or the gastroepiploic veins or in the aorta. Thus, NPY potentiated NA-evoked vasoconstriction predominantly in muscular arteries with alpha-1 adrenoceptors. NPY-related peptides, such as peptide YY and to some extent pancreatic polypeptide shared this ability, whereas calcitonin gene-related peptide or LPLRFamide did not. The mode of action by which NPY potentiates NA-evoked vasoconstriction was analyzed using the femoral artery. Pretreatment of the vessel with cocaine, a blocker of amine re-uptake, or rolipram, an inhibitor of phosphodiesterase, left the potentiation unaffected, whereas Na+ deficiency or ouabain, an inhibitor of Na+/K+-adenosine triphosphatase, abolished this effect of NPY. Nifedipine, a blocker of Ca++ entry, or removal of extracellular Ca++ shortly before the application of NPY had little effect. After prolonged exposure to a Ca++-free medium (with ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) the maximum response to NA was greatly reduced and the potentiating effect of NPY was abolished. Thus, the potentiation of NA-evoked vasoconstriction by NPY seems to depend upon the presence of Na+ but not upon a Ca++ influx. An intracellular sequestered Ca++ pool appears to play a critical role.

Animals↗
PubMed1984

Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers.

Neuropeptide Y (NPY)-immunoreactive nerve fibers were numerous around arteries and few around veins. NPY probably co-exists with noradrenaline in such fibers since chemical or surgical sympathectomy eliminated both NPY and noradrenaline from perivascular nerve fibers and since double staining demonstrated dopamine-beta-hydroxylase, the enzyme that catalyzes the conversion of dopamine to noradrenaline, and NPY in the same perivascular nerve fibers. Studies on isolated blood vessels indicated that NPY is not a particularly potent contractile agent in vitro. NPY greatly enhanced the adrenergically mediate contractile response to electrical stimulation and to application of adrenaline, noradrenaline or histamine, as studied in the isolated rabbit gastro-epiploic and femoral arteries. The potentiating effect of NPY on the response to electrical stimulation is probably not presynaptic since NPY affected neither the spontaneous nor the electrically evoked release of [3H]noradrenaline from perivascular sympathetic nerve fibers.

Animals↗
PubMed1984

Interaction of peptides present in perivascular nerves on the smooth muscle of cat cerebral arteries and on the stimulation-evoked efflux of 3H-noradrenaline.

Studies have been performed using isolated segments of the middle cerebral artery of the cat to determine whether noradrenaline (NA), neuropeptide Y (NPY), avian pancreatic polypeptide (APP), substance P (SP), vasoactive intestinal polypeptide (VIP) and gastrin releasing peptide (GRP) have effects that involve pre- and/or postsynaptic mechanisms. NA, clonidine, NPY and APP produced concentration-dependent contractions of cerebral artery segments, whereas SP and VIP induced relaxation of prostaglandin F2 alpha-contracted arteries. GRP, in the concentrations tested, (up to 2 X 10(-7)M) had no vasomotor activity. The alpha 2-adrenoreceptor agonist clonidine (10(-8) and 10(-6)M) produced a reduction in the field stimulation-evoked release of 3H-NA previously incorporated into the noradrenergic transmitter pool of the arteries, whereas the alpha 2-adrenoreceptor antagonist rauwolscine (10(-8) and 10(-6)M) resulted in increases in 3H-NA release. However, none of the peptides caused any significant change of the stimulation-evoked fractional release of 3H-NA. The results suggest that NPY, APP, SP and VIP have postjunctional effects in cat cerebral arteries and, in the concentrations tested do not affect stimulation-evoked NA release.

Animals↗
PubMed1984

Neuropeptide Y potentiates the effect of various vasoconstrictor agents on rabbit blood vessels.

The contractile effect of neuropeptide Y (NPY) was tested on isolated segments of basilar artery, central ear artery, gastro-epiploic artery and vein, and femoral artery and vein from the rabbit. At 30 nM NPY did not evoke vasoconstriction; at 300 nM NPY evoked a weak and variable response. NPY greatly potentiated the response of the gastro-epiploic and femoral arteries to noradrenaline without affecting the maximum response. As tested on the gastro-epiploic artery NPY was effective at concentrations of 1 nM and higher. As tested on the femoral artery the potentiating effect of 30 nM NPY on noradrenaline-evoked contractions was apparent immediately and 30 min after the application of NPY, but not after one hour. NPY (30 nM) potentiated the contractile response to noradrenaline and histamine but not to 5-hydroxytryptamine or high K+. The response to histamine was augmented in both arteries and veins, whereas the response to noradrenaline was enhanced in arteries but not in veins. NPY failed to potentiate the prostaglandin F2 alpha-evoked contraction except in the gastro-epiploic vein.

Animals↗