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Biomedical subjects

L Edvinsson

Publications and source records attributed to L Edvinsson.

At least 289 records · Page 16Linked to original sources
PubMed1990

Neuropeptide Y and the cerebral circulation.

The significance of neuropeptide Y (NPY) in the cerebral circulation has been examined in the rat using immunocytochemistry, isolated cerebral artery preparations, and quantitative autoradiographic techniques for determining local CBF and glucose utilisation. In the rat the middle cerebral artery and the lenticulostriate artery from which blood is supplied to the caudate nucleus were found to be invested with numerous perivascular NPY immunoreactive nerve fibres. NPY (3-300 nM) contracted rat middle cerebral artery segments in a concentration-dependent manner. Intracerebral microinjections of NPY (200 pmol) or vehicle (1 microliter) were performed in rats after full recovery from anaesthesia via previously implanted guide cannulae. Following injection of NPY into the striatum, local blood flow was markedly decreased by 36% throughout the ipsilateral caudate nucleus (e.g., from 104 +/- 25 to 67 +/- 15 ml 100 g-1 min-1; mean +/- SD), whereas glucose use in this region was not altered significantly (e.g., 73 +/- 8 and 74 +/- 10 mumol 100 g-1 min-1 with vehicle and NPY, respectively). Intrastriatal NPY did not alter CBF or glucose use in the majority of other brain areas, including all of the 40 contralateral regions examined and almost all regions within the ipsilateral hemisphere. In a small number of highly discrete brain areas remote from the injection site (e.g., amygdala), there were significant reductions in blood flow with minimal changes in glucose use. Since NPY is present around rat cerebral blood vessels, is capable of evoking their contraction, and has the ability to produce reductions in blood flow independently of oxidative metabolism, this neuropeptide may be of major importance in cerebrovascular regulation.

Animals↗
PubMed1990

Involvement of perivascular sensory fibers in the pathophysiology of cerebral vasospasm following subarachnoid hemorrhage.

The involvement of perivascular sensory fibers containing substance P (SP) and calcitonin gene-related peptide (CGRP) in the events occurring in conjunction with subarachnoid hemorrhage (SAH) has been studied in a rat model. Two days after blood injection, the time point at which maximum vasoconstriction is occurring in this model, immunocytochemistry and radioimmunoassay showed a reduction in SP- and CGRP-like immunoreactivity (LI). The quantitative measurements revealed a significant 50% reduction of CGRP-LI and a slight reduction of SP-LI in SAH as compared to controls. This partial reduction in neurotransmitter content (denervation) caused no change in the sensitivity of the rat basilar artery to SP or CGRP as studied using a sensitive in vitro method. However, the maximum relaxant response to CGRP was increased from 52 to 81% (p less than 0.05), while there was no change in the maximum SP-induced relaxations. It is suggested that not only a pre-, but also a postsynaptic modulation of perivascular sensory fibers may occur in experimental SAH.

Animals↗
PubMed1990

Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres.

In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal peptide-LI (VIP-LI), substance P-LI (SP-LI) and calcitonin generated peptide-LI (CGRP-LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY-LI and SP-LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY-LI and SP-LI were significantly increased. CGRP-LI was not altered, despite the fact that this peptide co-exists in many tissues with SP. There was no change in VIP-LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP-LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho-adrenal system.

Afferent Pathways↗
PubMed1990

Gamma 2-MSH in congestive heart failure: relation to atrial natriuretic peptide, arginine vasopressin and catecholamines.

A possible role of the proopiomelanocortin derived peptide gamma 2-melanocyte stimulating hormone (gamma 2-MSH) has been studied in patients with various degrees of congestive heart failure (CHF). The profile of changes in circulating levels of gamma 2-MSH-like immunoreactivity (-LI) has been compared with those of atrial natriuretic peptide (ANP)-LI, arginine vasopressin (AVP)-LI and catecholamines in CHF. Patients with moderate CHF (New York Heart Association stages I-II) showed significantly higher levels of h-alpha ANP-LI and NA (P less than 0.05) compared to controls. Patients with severe CHF (stages III-IV) had significantly higher levels of all hormones measured compared to controls: noradrenaline, P less than 0.001; adrenaline, P less than 0.001; gamma 2-MSH-LI, P less than 0.001; h-alpha ANP-LI, P less than 0.05; AVP-LI, P less than 0.01. For the catecholamines and gamma 2-MSH-LI there was a significant increase from moderate to severe forms of CHF. A significant correlation was observed between gamma 2-MSH-LI and noradrenaline, and between h-alpha ANP-LI and noradrenaline in patients with CHF. The present results show that gamma 2-MSH-LI is increased only in severe forms of cardiac failure, and that this change is more closely related to the increase in circulating levels of noradrenaline than to increased levels of ANP-LI or AVP-LI.

Aged↗
PubMed1990

Gamma 2-MSH increases during graded exercise in healthy subjects: comparison with plasma catecholamines, neuropeptides, aldosterone and renin activity.

To evaluate the possibility that the proopiomelanocortin (POMC)-derived peptide gamma 2-melanocyte stimulating hormone (gamma 2-MSH) has a role in circulatory regulation in man we studied circulating levels of this peptide at three different stages of physical activity in 10 young healthy subjects. The results were compared to simultaneously measured plasma levels of catecholamines, neuropeptide Y, vasopressin, renin activity, aldosterone and human alpha-atrial natriuretic peptide (alpha-hANP) and of the vasodilatory peptides calcitonin gene-related peptide, substance P and vasoactive intestinal peptide. The plasma levels of gamma 2-MSH-LI (like immunoreactivity) increased from 1009 +/- 101 pmol l-1 at supine rest to 1281 +/- 79 pmol l-1 when measured after 10 min walking (P less than 0.05), and remained at this increased level also after a consecutive further increase of physical activity (4 min stair rush), 1293 +/- 87 pmol l-1 (P less than 0.05 vs. at rest). The increase in circulating gamma 2-MSH-LI levels preceded the elevation of the venous plasma noradrenaline level, but did not rise further with more pronounced activation of the sympathetic nervous system at the highest grade of physical activity examined.

Aldosterone↗
PubMed1990

Cerebrovascular responses to capsaicin in vitro and in situ.

1. The cerebrovascular effects of capsaicin have been examined in vitro, in feline isolated cerebral arteries (circular segments, 2-3 mm long, 300-400 microns extended diameter) and, in situ, in pial arterioles (diameter 40-200 microns) on the cortical surface of chloralose-anaesthetized cats. 2. In isolated middle cerebral arteries, low concentrations of capsaicin (10(-14)-10(-10) M) effected a concentration-dependent relaxation of vessels precontracted with prostaglandin F2 alpha. This relaxant response was markedly attenuated by repeated administration of capsaicin but was minimally affected by the presence of atropine, propranolol, cimetidine or spantide in the tissue bath. 3. In isolated middle cerebral arteries, higher concentrations of capsaicin effected a marked concentration-dependent contraction. This contraction was not modified by 10(-6) M phentolamine or 10(-6) M ketanserin. A markedly reduced contraction by capsaicin was found upon the removal of calcium ions from the buffer solution. Also the calcium entry blocker nimodipine reversed the capsaicin-induced contraction. 4. Subarachnoid perivascular microapplication of capsaicin around individual pial arterioles in situ elicited a biphasic response (an immediate vasoconstriction followed by a sustained vasodilatation). The maximum vasoconstriction was a 60 +/- 6% reduction in diameter from base line and the maximum vasodilatation a 38 +/- 7% increase in diameter. Vasodilatation occurred at lower concentrations of capsaicin (EC50, approximately 5 x 10(-8) M) than those required for vasoconstriction (EC50 3 x 10(-7) M). 5. Trigeminal ganglionectomy 10-16 days before the microapplication abolished the in situ vasodilator effects of capsaicin (10(-6) M) applied perivascularly, but was without effect on the vasoconstrictor actions of this agent. 6. Repeated administration of capsaicin (10-6M) around the same arteriole resulted in a progressive attenuation of the vasodilator phase of the response, with no modification of the vasoconstrictor phase. 7. The present study suggests that capsaicin-induced cerebral vasodilatation is due to the release of vasoactive agents from cerebrovascular trigeminal nerve fibres, whereas the vasoconstrictor effect 6f capsaicin is due to a direct effect on the cerebral vasculature which is mediated via the transmembrane passage of extracellular calcium.

Animals↗
PubMed1990

Enhanced vasoconstrictor effect of endothelin in cerebral arteries from rats with subarachnoid haemorrhage.

The contractile response to endothelin has been examined in cerebral arteries from rats subjected to a prior subarachnoid haemorrhage (SAH) and compared with saline-injected controls. Endothelin elicited concentration-dependent contractions of rat basilar artery segments. The endothelin-induced contractions were much stronger in the SAH compared to control animals, which suggests a role in the pathophysiology of cerebral vasospasm.

Animals↗
PubMed1990

Analysis of endothelin-1-induced contractions of guinea-pig trachea, pulmonary veins and different types of pulmonary arteries.

Endothelin-I (ET-I), a peptide produced by the vascular endothelium, has been found to produce strong and persistent contractions of various blood vessels. In the present study, the effects of ET-I were studied on isolated pulmonary arteries from four different levels (main pulmonary artery, large lobar arteries, small lobar arteries and intrasegmental arteries) of the guinea-pig. In addition, the effects of ET-I on pulmonary arteries were compared with those of pulmonary veins and trachea. ET-I elicited a strong concentration-dependent contraction of pulmonary arteries, veins and trachea. The effects of ET-I were more pronounced in pulmonary arteries than in corresponding veins. Significant regional variations within the pulmonary arterial system were disclosed. The tracheal segments showed the same sensitivity and the same degree of relative maximal contraction as the pulmonary veins. Although the cellular mechanisms behind the action of ET still are not clear, our results favour a direct action of ET-I on the vascular smooth muscle during vasoconstriction. Furthermore, the ET-I-induced contraction in guinea-pig lung seems to be independent of extracellular calcium.

Animals↗
PubMed1990

Histamine receptors in brain vessels of guinea-pig: in-vitro pharmacology and ligand binding.

The subtype of histamine receptors in brain vessels of guinea-pig has been characterized by ligand binding and in-vitro pharmacology using selective antagonists. In the basilar artery histamine caused a concentration-related contraction with an EC50 of 1.6 +/- 0.3 microM. H1-receptor blockade with mepyramine and chlorpheniramine caused a displacement to the right of the histamine concentration-response curve with an apparent KD of 0.4 and 4.6 nM respectively, whereas H2-receptor blockade with cimetidine was without effect. Histamine did not induce any dilatory responses of vessels procontracted by 60 mM potassium-containing buffer in the presence or absence of histamine antagonists. Ligand-binding studies with [3H]mepyramine yielded a KD value of 5.5 nM in pial vessel membranes and 1.7 nM in the choroid plexus, confirming the presence of H1-receptors. Nimodipine caused a concentration-related blockade of histamine-induced contractions. Omission of Ca2+ from the extracellular medium for 30 min reduced the contractile responses to histamine in the basilar artery by 96%. Subsequent addition of Ca2+ caused concentration-related contractions which were inhibited by nimodipine. Thus, the histamine H1-receptor activation in guinea-pig basilar artery is coupled to dihydropyridine-sensitive Ca2+ channels.

Animals↗
PubMed1990

Hormonal influence on calcitonin gene-related peptide in man: effects of sex difference and contraceptive pills.

Calcitonin gene-related peptide (CGRP) is one of the peptides encoded for by the calcitonin gene. It has been demonstrated in man to be located in the thyroid and in perivascular nerves and to possess potent vasodilatory properties. In the present study we found plasma levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) to be significantly higher in females than in males and that women on contraceptive pills had significantly higher CGRP-LI levels than women not taking contraceptives. These data are in accordance with one earlier report on an increased CGRP level during pregnancy and suggest a positive influence of the female sex hormones on the plasma CGRP level in man, which should be considered in the establishment of a reference range for this analysis.

Adult↗
PubMed1990

Calcitonin gene-related peptide-LI in subarachnoid haemorrhage in man. Signs of activation of the trigemino-cerebrovascular system?

Calcitonin gene-related peptide (CGRP) is a neurotransmitter candidate together with the tachykinins in sensory fibres in the cerebral vasculature, with possible vasodilating properties. The origin of most of the CGRP-immunoreactive cerebrovascular nerve fibres seems to be the trigeminal ganglion. Experimentally produced vasoconstriction in cats after lesions of the trigeminal ganglion have shown marked prolonged constriction compared to controls. The possible involvement of the trigemino-cerebrovascular system as a defence system, with CGRP probably being the more potent vasodilatator, was investigated in 12 patients with subarachnoid haemorrhage (SAH). After operation with clipping of the aneurysm and treatment according to department policy, blood samples were taken from the external jugular vein on postoperative days 1, 2, 3, 5, 7, 9, frozen and analysed (radioimmunoassay) for CGRP-LI (-like immunoreactivity) levels. The patients were monitored with Doppler recordings from the middle cerebral arteries (MCA) and internal carotid arteries (ICA) following blood sampling. The relationship Vmean MCA/V mean ICA was used as an index of vasospasm. The highest CGRP-LI levels were found in the patient with highest velocities/index values. In patients with MCA aneurysms (n = 7), a correlation of r = 0.61 was found between the index and CGRP-LI levels. However, significant changes in the group as a whole was not found. The possible involvement of the trigemino-cerebrovascular system in SAH is discussed.

Adult↗
PubMed1990

Prevention of cerebral vasospasm in the rat by depletion or inhibition of substance P in conducting vessels.

Cisternal blood injection in the rat induces a biphasic angiographic vasospasm, with a maximal acute spasm at 10 minutes and a maximal late spasm at 2 days after the subarachnoid hemorrhage (SAH). Depletion of substance P-containing sensory nerves to the cerebral arteries with capsaicin prior to SAH prevents the development of both acute and late spasm. Intrathecal administration of the substance P antagonist spantide 2 hours prior to SAH also prevents the development of vasospasm, while spantide administration 1 hour before SAH only hinders the occurrence of late vasospasm. Intracisternal administration of spantide 2 hours post-SAH prevents the development of late vasospasm. This antagonist per se can induce a short-lasting dose-dependent angiographic vasoconstriction. Substance P-containing nerve fibers on the cerebral arteries could constitute the sensory link in a reflex arc system involved in the development of vasospasm in which the presence of blood in the subarachnoid space stimulates sensory substance P-containing nerve fibers on the cerebral arteries inducing a centripetal impulse to the A2-nucleus tractus solitarius setting into motion the events in the brain stem leading to acute and late vasospasm.

Animals↗
PubMed1990

Cerebral autoregulation.

Autoregulation of blood flow denotes the intrinsic ability of an organ or a vascular bed to maintain a constant perfusion in the face of blood pressure changes. Alternatively, autoregulation can be defined in terms of vascular resistance changes or simply arteriolar caliber changes as blood pressure or perfusion pressure varies. While known in almost any vascular bed, autoregulation and its disturbance by disease has attracted particular attention in the cerebrovascular field. The basic mechanism of autoregulation of cerebral blood flow (CBF) is controversial. Most likely, the autoregulatory vessel caliber changes are mediated by an interplay between myogenic and metabolic mechanisms. Influence of perivascular nerves and most recently the vascular endothelium has also been the subject of intense investigation. CBF autoregulation typically operates between mean blood pressures of the order of 60 and 150 mm Hg. These limits are not entirely fixed but can be modulated by sympathetic nervous activity, the vascular renin-angiotensin system, and any factor (notably changes in arterial carbon dioxide tension) that decreases or increases CBF. Disease states of the brain may impair or abolish CBF autoregulation. Thus, autoregulation is lost in severe head injury or acute ischemic stroke, leaving surviving brain tissue unprotected against the potentially harmful effect of blood pressure changes. Likewise, autoregulation may be lost in the surroundings of a space-occupying brain lesion, be it a tumor or a hematoma. In many such disease states, autoregulation may be regained by hyperventilatory hypocapnia. Autoregulation may also be impaired in neonatal brain asphyxia and infections of the central nervous system, but appears to be intact in spreading depression and migraine, despite impairment of chemical and metabolic control of CBF. In chronic hypertension, the limits of autoregulation are shifted toward high blood pressure. Acute hypertensive encephalopathy, on the other hand, is thought to be due to autoregulatory failure at very high pressure. In long-term diabetes mellitus there may be chronic impairment of CBF autoregulation, probably due to diabetic microangiopathy.

Cerebrovascular Circulation↗
PubMed1989

Calcium influx and protein kinase C activation involved in uterine vasoconstriction in guinea pigs.

The mechanical responses of circular segments of uterine arteries to different combinations of vasoactive agents and putative inhibitors of calcium fluxes were examined using a sensitive in vitro method. Exposure to high potassium (127 mM) or to noradrenaline (NA; 0.1 mM) resulted in a rapid, initial increase in tension of the vascular preparation to reach a sustained level of contraction (approximatively 12 mN) which lasted for at least 15 min. The protein kinase C activator, 4-beta-phorbol-12,13-esther-dibutyrate (10 microM), induced a slowly developing but sustained contractile response with a maximum (PDBumax) of only 4 mN. Addition of the calcium ionophore, A23187, to PDBu-contracted vessels did not increase tension, while the maximum tension evoked by A23187 per se (3 microM) was 5 mN. Ionomycin had only a small contractile effect on the uterine artery. The contraction evoked by depolarization (potassium) or alpha 1-adrenoceptor stimulation (NA) was decreased in nominally calcium-free medium containing EDTA (0-100 microM) or EGTA, while uterine arteries loaded intracellularly with the calcium chelator, quin-2, responded to the vasoconstrictors almost as well as the control preparations. Blockade of calcium influx with Cd2+ (greater than 0.01 mM), nifedipine (greater than 3 microM), verapamil (greater than 1 microM) and TMB-8 (greater than 10 microM) reduced the tension evoked by potassium somewhat more than it reduced the contractions induced by NA, while the opposite was seen in the presence of Ni2+ (greater than 0.1 mM). Inhibition of calmodulin-dependent enzymes by W7 (greater than 10 microM) reduced the maximum tension evoked by potassium and NA to a similar extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Co-existence of neuropeptides and differential inhibition of vasodilator responses by neuropeptide Y in guinea pig uterine arteries.

The co-localization of substance P (SP) with calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) with neuropeptide Y (NPY) of the guinea pig uterine artery were investigated with immunocytochemistry. The SP/CGRP fibre population was distinct from the VIP/NPY fibre population. Both types of fibres ran in the medial-adventitial border, and appeared as coarsed and fine varicosed. Uterine arterial dilatation was evoked by acetylcholine (ACh), SP, CGRP, and VIP in precontracted arteries as examined by a sensitive in vitro method. Strong relaxations were seen by ACh, CGRP and VIP. NPY had no relaxant effect per se but was found to be a potent inhibitor of vasodilation induced by ACh and SP, while relaxations induced by VIP and CGRP were unaffected. The functional significance of NPY in the uterine artery may to a large extent be to increase tension not only by potentiation of contraction but additionally by inhibiting vasodilator responses.

Animals↗
PubMed1989

Axonal tracing of autonomic nerve fibers to the superficial temporal artery in the rat.

The origin of nerve fibers to the superficial temporal artery of the rat was studied by retrograde tracing with the fluorescent dye True Blue (TB). Application of TB to the rat superficial temporal artery labeled perikarya in the superior cervical ganglion, the otic ganglion, the sphenopalatine ganglion, the jugular-nodose ganglionic complex, and the trigeminal ganglion. The labeled perikarya were located in ipsilateral ganglia; a few neuronal somata were, in addition, seen in contralateral ganglia. Judging from the number of labeled nerve cell bodies the majority of fibers contributing to the perivascular innervation originate from the superior cervical, sphenopalatine and trigeminal ganglia. A moderate labeling was seen in the otic ganglion, whereas only few perikarya were labeled in the jugular-nodose ganglionic complex. Furthermore, TB-labeled perikarya were examined for the presence of neuropeptides. In the superior cervical ganglion, all TB-labeled nerve cell bodies contained neuropeptide Y. In the sphenopalatine and otic ganglia, the majority of the labeled perikarya were endowed with vasoactive intestinal polypeptide. In the trigeminal ganglion, the majority of the TB-labeled nerve cell bodies displayed calcitonin gene-related peptide, while a small population of the TB-labeled neuronal elements contained, in addition, substance P. In conclusion, these findings indicate that the majority of peptide-containing nerve fibers to the superficial temporal artery originate in ipsilateral cranial ganglia; a few fibers, however, may originate in contralateral ganglia.

Animals↗