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Biomedical subjects

L Edvinsson

Publications and source records attributed to L Edvinsson.

At least 343 records · Page 19Linked to original sources
PubMed1987

Mechanisms of action of contrast media on cranial vessels. Comparison of diatrizoate, ioxaglate, iohexol, mannitol, and NaCl on rabbit basilar and ear arteries.

The relaxant effects of the ionic contrast media diatrizoate and ioxaglate and the nonionic agent iohexol on the vascular wall were examined by a sensitive in vitro system. Control solutions of NaCl and mannitol were used to evaluate the relative importance of osmolality to the vasodilation response. The rabbit central ear artery and the basilar artery were precontracted by (1) potassium, causing depolarization of the sarcolemmal membrane, (2) noradrenaline, causing activation of alpha 1-adrenoceptors, and (3) histamine, causing activation of histamine H1 receptors. The contrast media caused concentration-dependent relaxation of both types of arteries; this effect was relatively insensitive to the agent used to precontract the vessels. Histamine-contracted arteries were thought more sensitive to the relaxant agents used than arteries contracted by potassium or noradrenaline. The relaxation induced by the contrast media correlates with the relaxation induced by equiosmolar amounts of NaCl or mannitol. Our results suggest that the artery dilator response seen after exposure to currently used contrast media is due primarily to changes in local osmolality rather than to a specific receptor involvement.

Animals↗
PubMed1987

Characterization of tachykinin receptors in isolated basilar arteries of guinea-pig.

In circular lengths cut from the basilar artery of guinea-pig (0.2-0.3 mm o.d.) relaxations induced by substance P and neurokinin A were highly susceptible to mechanical damage of the endothelium by rubbing. The precontraction induced by prostaglandin F2 alpha but not that of 124 mM potassium was reduced considerably by the rubbing procedure. Concentration-dependent relaxations were evoked by tachykinin agonists in the following order of potency: substance P = physalaemin greater than neurokinin A greater than eledoisin. Physalaemin was, however, a partial agonist, giving only half the maximum relaxation as compared to the other tachykinins. The two putative tachykinin receptor antagonists, spantide ([D-Arg1, D-Trp7,9, D-Leu11] substance P) and [D-Pro2, D-Trp7,9] substance P, shifted the concentration-dependent relaxations of substance P to the right in a parallel manner. Calculation of pA2 values and Schild plot analysis revealed pA2 values of 7.4-7.6 for spantide and 6.9-7.0 for [D-Pro2, D-Trp7,9] substance P, irrespective of whether substance P or neurokinin A was used as agonist. The pA2 values and the Schild plot analysis suggest a specific interaction between tachykinin agonists and antagonists that follow a simple bimolecular process. The results suggest the presence of tachykinin receptors of the 'SP-P' type in guinea-pig basilar arteries which, for induction of relaxation, involves the release of an endothelium-derived relaxing factor.

Animals↗
PubMed1987

Direct vasomotor effects of theophylline and enprofylline on human coronary artery in-vitro: comparison with feline coronary and cerebral arteries.

The vasomotor effects of theophylline and enprofylline were investigated on circular segments of human coronary artery taken 6 h after death. Isolated arterial segments were examined using a sensitive myograph and isometric contractions were recorded with Grass transducers. The results were compared with those obtained in feline coronary and cerebral arteries. Theophylline and enprofylline induced pronounced relaxation of all types of precontracted arteries. In feline cerebral arteries the potency for eliciting relaxation was slightly higher for theophylline compared with enprofylline, while there was no difference in potency for the methylxanthines in coronary arteries. Prostaglandin F2 alpha frequently induced rhythmic contractions in human, but not in feline coronary arteries. Theophylline increased the amplitude of the rhythmic contractions while this was not seen following administration of enprofylline. Whether this mode of activity by theophylline contributes to its arrhythmogenic properties in-situ requires clarification.

Animals↗
PubMed1987

Interaction between extracellular magnesium and the passage of calcium through the sarcolemma during depolarization of isolated feline coronary and femoral arteries.

The mode of action of Mg2+ on vascular smooth muscle has been examined in isolated feline coronary and femoral arterial segments using a sensitive in vitro method. Potassium (124 mM) was added to feline coronary and femoral arteries incubated in a calcium-free buffer solution containing 10 microM EGTA, and magnesium in various concentrations (1.2, 4.4 or 13.2 mM). Potassium induced during these conditions a small contraction whose magnitude was attenuated by raised concentrations of Mg2+ (4.4 and 13.2 mM). Subsequent cumulative addition of calcium (10(-6)-3 x 10(-3) M) resulted in concentration-dependent contractions. The magnitude of these contractions was magnesium-dependent; the contraction elicited was depressed and a dextral shift of the extracellular calcium concentration-response relation was noted in the presence of increased concentrations of Mg2+ (4.4 and 13.2 mM). In separate experiments performed on potassium-depolarized (124 mM) feline coronary arteries it was noted that magnesium-induced relaxation was not changed by the presence of propranolol (10(-6) M), cimetidine (10(-6) M) or atropine (10(-5) M). In addition, the mechanical removal of the endothelium did not affect the dilator effect of Mg2+, as examined in potassium-depolarized (124 mM) feline femoral arteries. Hence, it may be concluded that Mg2+ may interfere with the passage of extracellular calcium through the sarcolemma, and that the dilator effect of magnesium is not the result of a direct action on beta-adrenoceptors, histamine H2 or cholinergic receptors, or requires the presence of an intact endothelium.

Adrenergic beta-Antagonists↗
PubMed1986

Characterization of adrenoceptor mechanisms in isolated guinea-pig uterine arteries.

The adrenoceptors of the guinea-pig uterine artery were characterized pharmacologically. Circular segments of the artery, approximately 2 mm long, and with an external diameter of 250 micron, were mounted in miniaturized tissue baths. Noradrenaline, methoxamine and phenylephrine (concentrations ranging from 10 nM to 1 mM), in the presence of propranolol (0.1 microM) and cocaine (1 microM), induced concentration-dependent contractions of the arterial segments. Clonidine (10 nM to 0.1 mM) was less effective in producing contraction of the vessel. Prazosin (10 nM to 1 microM) antagonized noradrenaline-induced contractions; its pA2 was 7.68. Rauwolscine (10 nM to 1 microM) had no effect on noradrenaline-induced contractions. Isoprenaline (10 nM to 0.1 mM) in the presence of prazosin (1 microM) and cocaine (1 microM) had no relaxant effect on arteries contracted submaximally by prostaglandin F2 alpha (5 microM). Cocaine or normetanephrine treatment did not influence the noradrenaline-induced contractions. It is concluded that in guinea-pig uterine arteries, amine-induced contractions are mediated predominantly by alpha 1-adrenoceptors and that in this arterial preparation, relaxant beta-adrenoceptor effects and neuronal or extraneuronal uptake are of minor if any importance.

Adrenergic alpha-Agonists↗
PubMed1986

Localization and effects of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide in human temporal arteries.

Nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) were seen in the adventitia or at the adventitia-media border of the human temporal artery. Pharmacological experiments on isolated temporal artery segments revealed that NPY potentiated the vasoconstrictor responses to noradrenaline, but had no vasoconstrictor ability or only a small vasoconstrictor ability per se. VIP, peptide histidine methionine 27 (PHM-27), SP, neurokinin A (NKA), and CGRP potently relaxed vessels precontracted by prostaglandin F2 alpha, the relative potency being CGRP greater than SP greater than NKA = VIP = PHM-27. The amount of relaxation varied between 67 and 91% of the prostaglandin F2 alpha-induced contraction. The peptide effects were not antagonized by classic adrenergic or cholinergic blockers, suggesting interactions via separate receptor sites.

Calcitonin Gene-Related Peptide↗
PubMed1986

Calcitonin gene-related peptide (CGRP): perivascular distribution and vasodilatory effects.

The distribution of perivascular nerve fibers displaying calcitonin gene-related peptide (CGRP) immunoreactivity and the effect of CGRP on vascular smooth muscle were studied in the guinea-pig. Perivascular CGRP fibers were seen in all vascular beds. Generally, they were more numerous around arteries than veins. Small arteries in the respiratory tract, gastrointestinal tract and genitourinary tract had numerous CGRP fibers. The gastroepiploic artery in particular received a rich supply of such fibers. Coronary blood vessels had a moderate supply of CGRP fibers. In the heart, a moderate number of CGRP fibers was seen running close to myocardial fibers. The atria had a richer supply than the ventricles. Numerous CGRP immunoreactive nerve cell bodies and nerve fibers were seen in sensory (trigeminal, jugular and spinal dorsal root) ganglia. Sequential or double immunostaining with antibodies against substance P and CGRP suggested co-existence of the two peptides in nerve cell bodies in the ganglia and in perivascular fibers. In agreement with previous findings CGRP turned out to be a strong vasodilator in vitro as tested on several blood vessels (e.g. basilar, gastroepiploic and mesenteric arteries). Conceivably, perivascular CGRP/SP fibers have a dual role as regulator of local blood flow and as carrier of sensory information.

Animals↗
PubMed1986

Effects of extracellular calcium and of the calcium entry blockers flunarizine and nimodipine on contractile responses in human temporal arteries.

Contraction induced by 124 mM potassium followed the depolarization of smooth-muscle cells and activation of potential-operated calcium channels in human temporal arteries. The contraction elicited consisted of two phases, one rapid and one slowly developing stable phase; both were affected by the two calcium entry blockers flunarizine and nimodipine but at significantly different concentrations. In calcium-free medium 124 mM potassium resulted in a weak contraction. Addition of calcium caused a concentration-dependent contraction that was attenuated by the calcium entry blockers at concentrations comparable to those inhibiting the second phase. The results suggested that in human temporal arteries flunarizine and nimodipine act as calcium entry blockers; there was good correlation with the therapeutic plasma concentration for nimodipine but not for flunarizine.

Calcium↗
PubMed1986

Calcitonin gene-related peptide: functional role in cerebrovascular regulation.

Distribution studies disclosed that all major cerebral arteries and cortical arterioles of the cat were invested with fine varicose nerve fibers that contained calcitonin gene-related peptide (CGRP)-like immunoreactivity; the trigeminal ganglia likewise contained CGRP immunoreactivity. Sequential immunostaining with antibodies to CGRP and to substance P (SP) revealed identical distributions of these two peptides in trigeminal ganglia and cerebrovascular nerve fibers, suggesting that CGRP and SP are colocalized in these nerves. CGRP completely disappeared from ipsilateral blood vessels after unilateral section of the trigeminal nerve. Exogenous CGRP was a potent relaxant of feline middle cerebral arteries in vitro (maximum relaxation, 10.5 +/- 1.5 mN; concentration eliciting half-maximal response, 9.6 +/- 1.3 nM). Perivascular microapplication of CGRP to individual cortical arterioles of chloralose-anesthetized cats provoked dose-dependent dilatations (maximum increase in diameter, 38 +/- 5%; concentration eliciting half-maximal response, approximately equal to 3 nM). CGRP was significantly more potent than SP as a cerebrovascular dilator, both in vitro and in situ. Chronic division of the ipsilateral trigeminal nerve in cats did not modify the magnitude of arteriolar responses to perivascular microapplication of either vasoconstrictor or vasodilator agents, but the duration of vasoconstrictor responses to norepinephrine (0.1 mM) or alkaline solutions (pH 7.6) was significantly increased. The cerebrovascular trigeminal neuronal system, in which CGRP is the most potent vasoactive constituent, may participate in a reflex or local response to excessive cerebral vasoconstriction that restores normal vascular diameter.

Animals↗
PubMed1986

Methylxanthines reduce in vitro human overall platelet metabolism as measured by microcalorimetry.

The effect in vitro of caffeine, theophylline and enprofylline on overall platelet metabolism was investigated by a sensitive microcalorimetric method. Platelet heat production rate was found to be decreased significantly in the presence of any of the three methylxanthines in mM concentrations. Also lower caffeine concentration, as occurring during normal coffee intake, reduced platelet metabolism. These results show that, firstly, methylxanthines have a direct influence on platelet metabolism, and secondly, microcalorimetry can be used as a new and sensitive tool for investigating the influence of drugs on blood cell metabolism.

Blood Platelets↗
PubMed1986

Microcalorimetric studies on the effect of adenosine receptor agonists and xanthine derivatives on overall metabolism in human platelets.

The direct overall metabolic effects of drugs acting on adenosine receptors in human platelets were evaluated using a sensitive microcalorimetric method. Adenosine induced a concentration-dependent increase in the heat production rate at concentrations above 100 microM. The adenosine uptake inhibitor, dipyridamole (3 microM) did not modify the effect of adenosine. Two putative adenosine receptor agonists were tested: NECA (5-N-ethyl carboxamide adenosine) and PIA (L-N6-phenylisopropyl-adenosine). NECA induced, at significantly lower concentrations than adenosine, an enhanced heat production rate. Concentrations above 1 mM had no effect. PIA, on the other hand, invariably induced a reduction in the heat production rate already at a concentration of 100 microM. The two xanthine derivatives enprofylline (25 microM) and theophylline (100 microM) were tested at concentrations found during antiasthmatic therapy. Neither had any thermogenic effect by themselves nor showed any significant modification of the heat production rate induced by adenosine (300 microM). These results indicate that adenosine and NECA increase human platelet metabolism, whereas PIA has an opposite effect. The proposed adenosine receptor antagonists enprofylline and theophylline were without effects. This microcalorimetric study gives new insights into the complex nature of adenosine mechanisms in a human test system and indicates that the thermogenic effect of adenosine is unrelated to adenosine receptors.

Adenosine↗
PubMed1986

Vasomotor responses of isolated human coronary arteries to magnesium, nitroglycerin and verapamil: a comparison with coronary arteries from cat and rat.

The vasomotor responses in vitro to magnesium, nitroglycerin and verapamil were investigated in human coronary arteries. In order to examine possible species differences in reactivity to these agents, experiments were performed also on cat and rat coronary arteries. Potassium (124 mM) regularly produced stable contractions suitable for experiments with dilator agents. The order of potency for eliciting relaxation was the same in all three species; verapamil greater than nitroglycerin greater than magnesium. Maximum relaxation induced by nitroglycerin or magnesium was significantly lower in arteries from cat as compared to that obtained in coronary artery segments from man and rat. Spontaneous rhytmic activity was often present in human coronary arteries but never in arterial segments from cat or rat. The rhytmic activity was frequently enhanced by the addition of prostaglandin F2 alpha (3 microM) to the tissue bath, on the other hand the rhythmic activity was depressed, or even abolished, by potassium (124 mM), magnesium (1.2-13.2 mM), nitroglycerin (2.2 X 10(-5) M) or verapamil (10(-8)-10(-7) M). The magnitude of the vasomotor response of feline coronary arteries to nitroglycerin or verapamil was dependent on the extracellular concentration of magnesium; in the presence of a high concentration of magnesium (4.4 mM) the dilator effect of nitroglycerin was enhanced while that of verapamil was slightly depressed. The dilator activity of the two agents was not changed by incubation of the vessel segments in a magnesium-free medium as compared to that obtained in the standard (1.2 mM Mg) buffer solution.

Adult↗
PubMed1986

Catecholamines and the relationship between cerebral blood flow and glucose use.

The effects of hypertension induced by norepinephrine and dopamine infusion on the relationship between local cerebral blood flow (CBF) and local glucose use (GU) were examined in rats with the use of quantitative autoradiographic techniques. After rats recovered from anesthesia, dopamine or norepinephrine was infused at a rate that ensured moderate hypertension [mean arterial blood pressure (MABP) approximately 150 mmHg]. During dopamine infusion (approximately 200 micrograms X kg-1 X min-1), overall CBF-to-GU ratio throughout the brain was elevated (P less than 0.0001) when compared with saline controls. In contrast, during norepinephrine infusion (approximately 10 micrograms X kg-1 X min-1), the overall CBF-to-GU relationship was not altered significantly. The differential effect of the catecholamines was a consequence of the marked increases in local CBF and moderate decreases in GU observed during dopamine infusion, whereas during norepinephrine administration CBF and GU were not significantly altered in most brain regions. Blood-brain barrier (BBB) permeability was increased during moderate hypertension induced by dopamine and not when induced by norepinephrine. During extreme hypertension (MABP greater than 165 mmHg), heterogeneous increases in CBF and BBB permeability occurred (e.g., in the cerebellum and thalamus). Thus the cerebrovascular response to catecholamine infusion was critically dependent on the agent administered, the level of hypertension achieved, and the brain region examined.

Animals↗
PubMed1986

Demonstration of perivascular peptides and changes in concentration with age in man.

By immunocytochemistry, human cerebral arteries have been found to be invested by perivascular fibres which contain neuropeptide Y, substance P and vasoactive intestinal polypeptide (VIP). The concentrations of the peptides are comparable for substance P and VIP, whereas that of neuropeptide Y is much higher. A marked reduction in radioimmunoassayable peptide levels was observed with advancing age of the patients.

Adolescent↗
PubMed1986

On the pathogenesis of regional cerebral ischemia in intracranial hemorrhage: a causal influence of potassium?

Cerebral ischemia and intracranial hemorrhage are the most important causes of perinatal brain damage and their pathogenesis seems to be interrelated. Several components in blood have been shown to cause contraction of cerebral blood vessels. In the present study we examined the changes with time of the concentration of standard electrolytes in a mixture of blood and mock cerebrospinal fluid, whether these changes may affect cerebrovascular tone, and if calcium blockers could influence such an effect. Extracellular K+ increased to about 23 mM 4 days after mixing when half of the mixture consisted of blood, and remained nearly constant for at least 8 days thereafter. Using isometric recording of circular tension in a controlled tissue bath it was found that isolated human pial arterioles, small arteries, and feline middle cerebral arteries contracted markedly when K+ exceeded 10 and 20 mM, respectively. It is concluded that neonatal perihemorrhagic ischemia may be, at least partly, due to leakage of K+ from the erythrocytes. The contractile effect of extracellular K+ is effectively counteracted by Ca++ entry blockers, which therefore may have a role in the prevention of perihemorrhagic ischemia in neonates.

Animals↗