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Biomedical subjects

L Edvinsson

Publications and source records attributed to L Edvinsson.

At least 307 records · Page 17Linked to original sources
PubMed1989

Gamma 2-MSH immunoreactivity in the human heart.

In patients undergoing aorto-coronary by-pass surgery, we found a 26% arterial-venous difference of immunoreactive gamma 2-melanocytostimulating hormone (MSH), a proopiomelanocortin (POMC) derived peptide known to possess profound hemodynamic effects. These results prompted an investigation of the presence of gamma 2-MSH in the human heart. Using a two-step extraction procedure, regions of human hearts were examined by sensitive and specific radioimmunoassays to determine their gamma 2-MSH content. Mean (+/- SEM) concentrations of 0.14 +/- 0.023 pmol/g and 0.12 +/- 0.017 were found in right atrium and right ventricle, respectively. High performance liquid chromatography indicated that 80-90% of the total immunoreactivity eluted in a single sharp peak in a position identical to that of synthetic gamma 2-MSH.

Chromatography, High Pressure Liquid↗
PubMed1989

Comparison of peptidergic mechanisms in different parts of the guinea pig superior mesenteric artery: immunocytochemistry at the light and ultrastructural levels and responses in vitro of large and small arteries.

The presence and distribution of peptide-containing nerve fibres and axon terminals have been studied in the proximal part of the superior mesenteric artery (SMA) (i.e. conductance vessel) and in the finer ramifications of the SMA close to the intestine (outer diameter 200 microns, i.e. resistance vessel). Light microscopic immunocytochemistry revealed that the proximal part of the SMA possessed a rich supply of neuropeptide Y (NPY)- and tyrosine hydroxylase (TH)-immunoreactive nerve fibres, forming a loose perivascular network which increased in density distally. The vasoactive intestinal peptide (VIP) immunoreactivity was moderate in the proximal artery and only a few VIP fibres could be identified in the distal portion of the SMA. Calcitonin gene-related peptide (CGRP)-, neurokinin (NK)- and substance P (SP)-immunoreactive fibres had an intermediate density in both arterial regions, but their distribution pattern varied. Electron microscopic immunocytochemistry showed that NPY-immunoreactive nerve terminals were close to the smooth muscle cells of the medial layer in both parts of the SMA, indicative of a vasomotor role. Although the VIP-immunoreactive terminals had a similar localization they were seen less frequently. CGRP-, NK- and SP-immunoreactive axons had an identical distribution in the two vascular regions. Interestingly, they were usually seen more distant from the medial layer, localized in the adventitia. Examination of vasomotor responses to perivascular peptides revealed significant regional differences: NPY produced only weak contractions (13 +/- 3%) of proximal vessel segment of the conductance type, while strong concentration-dependent contractions were seen in distal parts of the SMA (resistance vessel). In neither region was any interaction with noradrenaline demonstrated. Proximal segments of the SMA revealed a stronger and more potent response to VIP and peptide histidine isoleucine than did distal segments, while on the other hand acetylcholine was more potent and elicited stronger effects in distal segments. CGRP, NKA and SP relaxed precontracted arteries by 50-75% and there was no significant difference in responsiveness to these peptides in the two regions of the SMA.

Animals↗
PubMed1989

Neuronal pathways to the rat middle meningeal artery revealed by retrograde tracing and immunocytochemistry.

The origin of nerve fibers to the middle meningeal artery of rat was studied by retrograde tracing in combination with immunocytochemistry. Application of the retrograde tracer, True blue (TB), to the middle meningeal artery labeled nerve cell bodies in the ipsilateral superior cervical ganglion, the otic ganglion, the sphenopalatine ganglion, the jugular-nodose ganglionic complex, the trigeminal ganglion and the cervical dorsal root ganglion at level C2. A few nerve cell bodies were labeled in the contralaterally placed ganglia. Judging from the number of labeled nerve cell bodies, the ipsilateral superior cervical ganglion, the otic ganglion, the sphenopalatine and the trigeminal ganglia contribute most to its innervation. A moderate supply of labeled nerve cell bodies was seen in the cervical dorsal root ganglion at level C2 whereas there were only few in the jugular-nodose ganglionic complex. The TB-labeled nerve cell bodies were further examined for the presence of neuropeptides. For that purpose antibodies against neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP) were used. Most of the TB-labeled nerve cell bodies in the superior cervical ganglion exhibited NPY-immunoreactivity. In the sphenopalatine and otic ganglia the majority of the TB-labelled neurons were VIP-immunoreactive whereas in the trigeminal and dorsal root ganglion at level C2 the majority of labeled nerve cell bodies displayed CGRP-immunofluorescence and a minority of the labeled nerve cell bodies were substance P-immunoreactive. Together the findings indicate that several ganglia project to the middle meningeal artery of the rat and that many neuropeptides are involved in vasomotor control and in mediation of afferent information.

Animals↗
PubMed1989

Involvement of perivascular neuropeptide Y nerve fibres in uterine arterial vasoconstriction in conjunction with pregnancy.

The perivascular neuropeptide Y (NPY) innervation and its relation to adrenergic nerves of uterine arteries from non-pregnant and pregnant guinea pigs was analyzed immunocytochemically. The NPY content of the uterine artery was, in addition, measured radioimmunologically (RIA). Vasomotor effects of NPY per se and in combination with other vasoconstrictors were examined using a sensitive in vitro method. Pregnancy did not visibly affect density and distribution of NPY-immunoreactive fibres. The NPY fibres contained in addition immunoreactivity to dopamine-beta-hydroxylase (marker for noradrenergic neurons). RIA revealed a slight decrease of NPY content during pregnancy, probably due to the increased smooth muscle volume of uterine arteries. The contractile effect of NPY on uterine arteries was weak, while vasoconstriction induced by various agonists was potentiated by NPY, particularly during pregnancy. It is concluded that perivascular NPY-containing nerve fibres may be involved in the dramatic blood flow alterations that occur in the uterine circulation in connection with pregnancy and partus.

Animals↗
PubMed1989

Mechanisms of action of endothelin on isolated feline cerebral arteries: in vitro pharmacology and electrophysiology.

Vascular endothelium has been found to produce a strong and potent vasoconstrictor peptide, endothelin. In this study, we have examined basic mechanisms underlying the contractile response of cerebral vessels to endothelin using in vitro pharmacology and electrophysiology. It was found that endothelin produced strong concentration-dependent contractions of circular segments of the feline middle cerebral artery. The response was slow in onset and long lasting. The vessels showed a remarkably strong tachyphylactic reaction upon repeated exposure to endothelin. The contractile effect of endothelin was not modified by the alpha-adrenoceptor antagonist phentolamine (10(-6) M) or the 5-hydroxytryptamine antagonist ketanserin (10(-6) M). Mechanical removal of the endothelium decreased potassium contractions while the maximum response to endothelin was only slightly reduced. There was no change in sensitivity of the cerebral artery to endothelin. The addition of a calcium antagonist (10(-6) M diltiazem or 3 X 10(-8) M nimodipine) or removal of extracellular calcium from the buffer solution did not change the sensitivity of the artery to endothelin but the maximum response to endothelin was reduced by between 40 and 60% by these procedures. The resting membrane potential of the cat middle cerebral artery was -62.8 +/- 3.5 mV. There was no significant depolarization in conjunction with cumulative administration of endothelin in concentrations below 1 X 10(-9) M. However, bursts of excitatory junction potentials were occasionally seen in response to high concentrations of endothelin (5 X 10(-9) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Acetylcholine and vasoactive intestinal peptide in cerebral blood vessels: effect of extirpation of the sphenopalatine ganglion.

The innervation of cerebral blood vessels by nerve fibers containing acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) and the vasomotor effects of the two neurotransmitters have been analyzed in the rat following the uni- or bilateral removal of the sphenopalatine ganglion (SPG), which is thought to be the major origin of this innervation. Histochemistry of AChE-positive nerve fibers and the immunoreactivity toward VIP revealed only a 30% reduction in the innervation pattern of the rostral part of the cerebral circulation following the operation. At approximately 4 weeks postoperatively, the original nerve network was restored. Quantitative measurements of cholineacetyltransferase activity and VIP revealed similar reductions in the levels of collected large cerebral arteries at the base of the brain and in small pial vessels overlying the cerebral cortex at the various postoperative times following uni- or bilateral removal of the SPG. The two techniques thus complemented each other. Vasomotor reactivity to acetylcholine (ACh) and VIP was examined in proximal segments of the middle cerebral artery at the various postoperative times. Generally, the removal of the SPG had no effect on the responses to ACh or VIP. The evidence indicates that only approximately one-third of the cholinergic/VIP innervation of the rostral part of the cerebral circulation originates in the SPG.

Acetylcholine↗
PubMed1989

Retrograde tracing of nerve fibers to the rat middle cerebral artery with true blue: colocalization with different peptides.

The origin of nerve fibers to the rat middle cerebral artery was studied by retrograde tracing with the fluorescent tracer True Blue (TB) in combination with immunocytochemistry to known perivascular peptides. Application of TB to the middle cerebral artery labeled nerve cell bodies in the ipsilateral superior cervical ganglion, the otic ganglion, the sphenopalatine ganglion, the trigeminal ganglion, and the cervical dorsal root ganglion at level C2. A few labeled nerve cell bodies were seen in contralateral ganglia. Judging from the number and intensity of the labeling, the superior cervical ganglion and the trigeminal ganglion and dorsal root ganglion at level C2 contributed most to the innervation. A moderate number of nerve cell bodies were labeled in the sphenopalatine and otic ganglia. The TB-labeled nerve cell bodies were further examined for the presence of neuropeptides. For that purpose antibodies raised against neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) were used. A considerable portion of the TB-labeled nerve cell bodies in the superior cervical ganglion contained NPY. About half of the labeled nerve cell bodies in the sphenopalatine and otic ganglia contained VIP. In the trigeminal ganglion and in the dorsal root ganglion at level C2, one-third of the TB-labeled nerve cell bodies were CGRP-immunoreactive, while only few nerve cell bodies contained SP. The study provides direct evidence for the origin of cerebrovascular peptidergic nerve fibers and demonstrates that not only ipsilateral but also contralateral ganglia contribute to the innervation of the cerebral circulation.

Animals↗
PubMed1989

Circulating perivascular dilatory neuropeptides in hypertension.

Little is known about perivascular neuropeptides in hypertension in man. In this study we investigated the circulating levels of calcitonin gene-related peptide (CGRP)-, substance P- and vasoactive intestinal peptide-like immunoreactivity in 30 patients with severe hypertension before and after treatment for high blood pressure. Circulating levels of CGRP- and substance P-like immunoreactivity in the hypertensives were significantly different from the corresponding levels in 31 age- and sex-matched normotensive subjects. After normalization of blood pressure the mean levels of CGRP- and substance P-like immunoreactivity did not differ between the two groups. The levels of vasoactive intestinal peptide-like immunoreactivity remained unchanged. These observations suggest that vascular afferent nerves play a part in the maintenance of hypertension.

Adult↗
PubMed1989

Pharmacological characterization of histamine receptors in the human temporal artery.

1. The subtypes of histamine-receptors which mediate dilatation of small human temporal arteries have been characterized in vitro using 'selective' agonists and antagonists. 2. Dilatory responses were studied after preconstriction with prostaglandin F2 alpha since contraction was not seen at histamine concentrations up to 10(-4) M. Histamine caused a concentration-related relaxation of cerebral vessels with an IC50 value of 2.8 +/- 0.6 X 10(-7) M. 3. Cimetidine caused a parallel shift to the right of the histamine concentration-response curve whereas mepyramine was without observable effect. This suggests the presence of histamine H2-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 the histamine H1-receptor subtypes, simple competitive antagonism at H2-receptors can be revealed with a pA2 value of 6.58 for cimetidine. The apparent pA2 value for mepyramine was 8.58. 4. The 'selective' H1-receptor agonists pyridylethylamine, 2-methylhistamine and thiazolylethylamine, and the H2-receptor agonists dimaprit, impromidine and 4-methylhistamine all mimicked the histamine response, but all except impromidine were less potent than histamine. The order of potency was impromidine greater than thiazolylamine greater than 4-Me-histamine greater than 2-Me-histamine greater than dimaprit greater than pyridylethylamine greater than tele-Me-histamine. 5. These results indicate that the histamine-induced dilatation in small human temporal arteries is mediated by both H1- and H2-receptors and that the latter subtype of histamine receptors predominates.

Adult↗
PubMed1989

Peptide-containing nerves in the rat femoral artery and vein. An immunocytochemical and vasomotor study.

Peptide-containing nerves have been examined in the rat femoral artery and vein using immunocytochemical and vasomotor techniques. The general neuronal marker PGP 9.5 revealed a moderate supply of nerve fibres and fascicles forming a loose network in the adventitia and the adventitial-medial border of the artery and vein. The majority of the nerve fibres in both the artery and vein displayed immunoreactivity for neuropeptide Y (NPY) and tyrosine hydroxylase (TH). The distribution pattern and number of these two types correlated well. The artery had a slightly richer PGP 9.5- immunoreactive nerve supply compared to the vein, but the nerve plexus in the vein displayed a more uniform arrangement. In contrast, relatively few nerve fibres displayed calcitonin gene-related peptide, substance P, or vasoactive intestinal peptide immunoreactivity in either the artery or vein. The calcitonin gene-related peptide immunoreactive fibres had a similar distribution to that of the substance P containing fibres. Using a sensitive in vitro method the vasomotor responses to perivascular peptides were characterized. In the femoral artery NPY potentiated alpha 1-adrenoceptor mediated contractions, and had very little effect by itself. In contrast, 10(-7) M NPY contracted femoral veins by up to 68% relative to 60 mM potassium induced contraction, and there was no potentiation of alpha-adrenoceptor mediated contractions. Acetylcholine, peptide histidine isoleucine, vasoactive intestinal peptide, substance P and calcitonin gene-related peptide, all relaxed the contracted femoral artery and vein. Regarding the putative parasympathetic neurotransmitters, acetylcholine caused stronger relaxation of veins as compared to arteries whereas for vasoactive intestinal peptide and peptide histidine isoleucine the relaxations were stronger in the arterial preparation. These three agonists were more potent in the femoral vein. Substance P was more potent on the femoral vein, having the same maximum response in both preparations. On the other hand, the response induced by CGRP was some three times greater in the venous than in the arterial preparation. These data reveal that although there appear to be only minor differences in the peptidergic innervation of the rat femoral artery and vein pronounced differences occur in the peptide effector responses. The data support the concept that perivascular peptides play different roles in regulating various parts of the circulation.

Acetylcholine↗
PubMed1989

Effects of calcium entry blockers on human platelet metabolism measured by microcalorimetry.

1. The direct overall metabolic effects of calcium entry blockers on human platelets were evaluated using a sensitive microcalorimetric method. 2. The effect on platelet metabolism of four calcium entry blockers with different profiles of action was examined and compared with the relaxant response on human cerebral vessels in vitro. 3. Diltiazem (10(-8), 10(-4) M) and nifedipine (10(-10), 10(-6) M) were without effect on overall platelet metabolism. On the other hand flunarizine (10(-4) M) and verapamil (10(-4) M) significantly reduced metabolism, while lower concentrations of these agents did not change heat production. 4. The thermogenic response occurred at concentrations of the calcium entry blockers that were much higher than those observed during therapy and the concentrations which relax human cerebral arteries in vitro.

Blood Platelets↗
PubMed1989

Reduced levels of calcitonin gene-related peptide (CGRP) but not substance P during and after treatment of severe hypertension in man.

Little is known of the significance of perivascular peptides in hypertension. In this study we have investigated the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P- like immunoreactivity (SP-LI) during and after treatment of severe hypertension. Seventeen patients with a mean blood pressure of 204/127 mmHg were included. Circulating levels of CGRP-LI and SP-LI in normotensive controls were 35 +/- 4 and 1.2 +/- 0.1 pmol/l, respectively. In the hypertensives CGRP-LI was significantly lower (22 +/- 3 pmol/l: P less than 0.05) while SP-LI did not differ (1.6 +/- 0.3 pmol/l) from the normotensives. After treatment the circulating level of CGRP-LI was still significantly lower (16 +/- 2 pmol/l: P less than 0.001) while SP-LI remained unchanged when compared with the controls. These observations suggest an involvement of vascular afferent nerves in the aetiology of hypertension in man.

Adrenergic beta-Antagonists↗
PubMed1989

Neuropeptides in the cerebral circulation.

The occurrence and distribution of peptide-containing nerve fibers to the cerebral circulation are described. Immunocytochemical studies have revealed that cerebral blood vessels are invested with nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI), substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP). In addition, there are studies reporting the occurrence of putative neurotransmitters such as cholecystokinin, dynorphin B, galanin, gastrin releasing peptide, vasopressin, neurotensin, and somatostatin. The nerves occur as a longitudinally oriented network around large cerebral arteries. There is often a richer supply of nerve fibers around arteries than veins. The origin of these nerve fibers has been studied by retrograde tracing and denervation experiments. These techniques, in combination with immunocytochemistry, have revealed a rather extensive innervation pattern. Several ganglia, such as the superior cervical ganglion, the sphenopalatine ganglion, the otic ganglion, and small local ganglia at the base of the skull, contribute to the innervation. Sensory fibers seem to derive from the trigeminal ganglion, the jugular-nodose ganglionic complex, and from dorsal root ganglia at level C2. The noradrenergic and most of the NPY fibers derive from the superior cervical ganglion. A minor population of the NPY-containing fibers contains VIP instead of NA and emanates from the sphenopalatine ganglion. The cholinergic and the VIP-containing fibers derive from the sphenopalatine ganglion, the otic ganglion, and from small local ganglia at the base of the skull. Most of the SP-, NKA-, and CGRP-containing fibers derive from the trigeminal ganglion. Minor contributions may emanate from the jugular-nodose ganglionic complex and from the spinal dorsal root ganglia. NPY is a potent vasoconstrictor in vitro and in situ. VIP, PHI, SP, NKA, and CGRP act via different mechanisms to induce cerebrovascular dilatation. The sympathetic, the parasympathetic, and the sensory systems appear to be involved in modulating cerebrovascular tone in hypertension and in conditions of threatening vasoconstriction, e.g., subarachnoid hemorrhage and migraine.

Cerebrovascular Circulation↗
PubMed1988

Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system.

The trigeminal ganglion was activated, in humans by thermocoagulation as part of the treatment of trigeminal neuralgia and in cats by electrical stimulation, and blood samples were taken from the external jugular vein for estimates of plasma levels of substance P and calcitonin gene-related peptide (CGRP). In those patients who were noted at the time of coagulation to have flushed there were marked elevations of the local (cranial) levels of both peptides. However, in the nonflushing patients no changes in the peptide levels were observed. Parallel experiments in the cat revealed that the levels of substance P-like and CGRP-like immunoreactivity were increased during electrical stimulation of the trigeminal ganglion. The observation of elevation of substance P-like and CGRP-like immunoreactivity after activation of the nociceptive afferent system of the head provides new insights into a putative role of peptides in the pathophysiology of migraine and cluster headache, and suggests new areas of possible therapeutic intervention.

Animals↗
PubMed1988

Digoxin, magnesium, and potassium levels in a forensic autopsy material of sudden death from ischemic heart disease.

In 91 cases where the cause of death was heart disease, digoxin, Mg and K concentrations in serum and ventricular myocardium were measured post mortem. Forty per cent were positive for digoxin in both serum and myocardium. The mean serum level was 5.1 +/- 2.4 nmol/l and the mean myocardial level was 42.6 +/- 27.5 ng/g. Correlation could be established between serum and myocardial concentrations of digoxin. There were statistically significant differences in serum as well as in myocardial digoxin levels in persons on 0.13 mg and 0.25 mg per day, respectively. Myocardial levels of Mg and K were low as generally found in persons with ischemic heart disease. There was no correlation between these levels and myocardial digoxin concentrations. Caution must be exercised in the assessment of digoxin results from cadaver samples because of the postmortem rise of digoxin serum concentrations. Considering this fact, the results still indicate that the prevalence of toxic digoxin concentrations might be more common than previously thought.

Adult↗
PubMed1988

Neurokinin A in cerebral vessels: characterization, localization and effects in vitro.

Nerve fibres displaying neurokinin A (NKA)-immunoreactivity (IR) were seen in trigeminal nerve cell bodies and around cerebral blood vessels. NKA-positive fibres had the same general distribution as those displaying substance P (SP)-IR. Double or sequential immunostaining revealed coexistence of NKA- and SP-IR in a population of small nerve cell bodies in the trigeminal ganglion and in perivascular nerve fibres of brain vessels; both tachykinins were also noted to coexist with calcitonin gene-related peptide (CGRP)-IR. The presence of NKA- and SP-IR in cerebral vessels from guinea pig was verified by high-performance liquid chromatography and radioimmunochemistry. The levels NKA-IR were higher than those of SP-IR in cerebral vessels of rat, guinea pig and rabbit. In cat, pig, cow and human brain vessels, the levels of NKA- and SP-IR were equal. Major cerebral vessels at the base of the brain contained higher levels of NKA- and SP-IR than pial vessels on the cerebral convexities. Only low levels of NKA-IR and SP-IR were measured in choroid plexus and dura mater. Precontracted isolated arterial segments of middle cerebral (cat), basilar (rabbit, guinea pig and rat) and pial arteries (man) relaxed following the in vitro administration of NKA and SP. The responses occurred in the same concentration range; the IC50 value for NKA was, however, about 10 times higher than that for SP, while the maximum relaxation was equal. In basilar arteries from guinea pig, the peptides NKA, SP and CGRP all induced strong and potent relaxations. There was no evidence that one of the peptides might potentiate the relaxant effects in vitro of another. The present data suggest that NKA, SP and CGRP are costored and can be released together and cooperate in the mediation of vascular reactions in response to activation of the trigemino-cerebrovascular pathway.

Animals↗
PubMed1988

Effect of stimulation of the sphenopalatine ganglion on cortical blood flow in the rat.

The effects of electrical stimulation of the sphenopalatine ganglion on cortical blood flow and gas partial pressures (PO2 and PCO2) were studied in the anesthetized rat. Tissue PO2, PCO2, and local CBF were measured simultaneously in both parietal cortices by means of mass spectrometry. Stimulation of the sphenopalatine ganglion increased CBF and tissue PO2 by approximately 50 and 20%, respectively, in the ipsilateral parietal cortex. Smaller but significant increases in CBF and tissue PO2 were simultaneously seen in the contralateral parietal cortex. These variations were also accompanied by small decreases in PCO2 in both parietal cortices and a 5% increase in mean arterial pressure, whereas cortical electrical activity did not change. We conclude that the cholinergic (and vasoactive intestinal polypeptidergic) innervation of the cerebral blood vessels, arising from the sphenopalatine ganglion has significant vasomotor potential and that this system may be of functional importance.

Acetylcholine↗