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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extensive plexuses of serotonin axons form a supra- and subependymal system in the walls of the ventricles, in the arachnoid sheath around major cerebral blood vessels, and in the pia over the spinal cord. These have been demonstrated by autoradiography after continuous intraventricular perfusions of exogenous [3H]5-HT in rats and monkeys. The axons accumulate 5,6-DHT rendering them electron opaque, but have no uptake systems for [3H]NE. After treatment with MAO inhibitors and [3H]5-HT, the axonal boutons contain large (70nm) variably dense synaptic vesicles, and small (35 nm) vesicles each equipped with a dense dot. The latter vesicles are not seen in untreated controls. Electrical stimulation in the raphe nuclei causes significant increases in axonal [3H]5-HT uptake indicating that the fibers originate in the raphe. Quantitatively, the supraependymal plexus is variable, profuse over the dorsal and ventral aqueductal surfaces, sparse over the lateral aspects. Individual raphe neurons have their specific uptake affinities for [3H]5-HT that are independent of tracer concentration or diffusion gradient. It is suggested that raphe neurons with low 5-HT uptake may utilize other neurotransmitters. Two new functional roles are proposed: (1) the serotonin ventricular and pial axons are probably important modifiers of local cerebrospinal fluid (CSF) composition so that regional CSF variations in 5-HT and its metabolites are highly probable; (2) the subarachnoid plexus around major cerebral vessels may contribute to local vasomotor action, thus affecting the cerebral blood flow. The possible significance of these serotonin systems for an understanding of certain neurological entities such as migraine and hemodynamic regulation in cerebral vascular disease is indicated.
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PMID:Serotonin axons in the supra- and subependymal plexuses and in the leptomeninges; their roles in local alterations of cerebrospinal fluid and vasomotor activity. 81 16

Cardiovascular disease is a major cause of death. There is evidence that this disease is predicted and its progression influenced by various factors (e.g. hyperlipidaemia). In this review, we consider aspects of platelet structure and function which may explain how this cell type contributes to the pathogenesis of vascular disease. The platelet also contains bioamines (serotonin, 5-HT; histamine) which are potent vasoactive substances. Studies involving patients with peripheral vascular disease (PVD) where abnormalities in platelet function (platelet aggregation and platelet shape change) and in bioamine status (vascular, platelet and plasma bioamine concentrations) are reviewed. We also discuss how platelet activation (in vitro) and plasma lipids influence intraplatelet bioamine status. Finally, we report in vitro evidence of the effect of two drugs prescribed to PVD patients: aspirin and naftidrofuryl. Aspirin is an ineffective inhibitor of 5-HT-induced whole blood platelet aggregation whereas naftidrofuryl is effective in the presence or absence of aspirin. By identifying and altering the factors which contribute to the pathogenesis of atherosclerosis we will be better equipped to prevent, reverse or retard this process.
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PMID:Serotonin, histamine and platelets in vascular disease with special reference to peripheral vascular disease. 134 86

5-Hydroxytryptamine (5-HT; serotonin) has long been implicated in the aetiology of migraine but the evidence remains circumstantial and certainly not definitive. Numerous papers have reviewed the background which is briefly outlined here. Although the continued belief in the primary involvement of 5-HT in the genesis of a migraine attack has recently been questioned, many antimigraine drugs undeniably interact potently with 5-HT receptors. It can be argued, however, that their modest clinical benefit results from their pharmacological effects, be they mediated through 5-HT receptors or otherwise, independently of any pathophysiological involvement of endogenous 5-HT. Nevertheless, there seems convincing evidence that central release of 5-HT by various drug mechanisms causes migraine-like headache in migraineurs. It remains to be seen whether these drugs mimic the pathological event initiating the spontaneous migraine attack. Regardless of these considerations, the focus of research on 5-HT and migraine has proved to be enormously profitable over several decades, culminating recently in the identification of a novel, potentially important, antimigraine drug for the treatment of the acute attack. This drug, sumatriptan, is a selective cranial vasoconstrictor which mediates this effect by specifically activating a particular 5-HT1 receptor subtype. Undoubtedly a precise understanding of its clinical mechanism of action, which is currently being studied by a number of groups, will lead to a better understanding of the pathogenesis of migraine. Perhaps this in turn will help in finally determining whether migraine is a vascular disease and whether or not a disturbance of 5-HT is just epiphenomenal or is truly the primary initiating pathological event.
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PMID:5-Hydroxytryptamine and the pathophysiology of migraine. 204 30

Consumption of monosodium glutamate has long been considered to precipitate headaches in susceptible patients. In this study the direct effects of glutamate and its metabolite, glutamine, on arterial contractility were examined using rings of rabbit aorta. In a high concentration glutamate caused significant concentration-dependent contractions (EC50, 10(-1)M; maximum tension, 188.4 +/- 33.3 mg wt tension/mg tissue). Agonists and antagonists for alpha-adrenergic, histaminergic, serotonergic, cholinergic, and GABA-nergic receptors as well as inhibition of prostaglandin synthesis failed to influence glutamate contractions. At high concentrations (10(-5)M) the calcium channel blocker, verapamil, inhibited the glutamate response. Glutamate and glutamine both exhibited concentration dependent relaxation of norepinephrine (NE), phenylephrine (PE), histamine, serotonin (5-HT), and prostaglandin F2 alpha (PGF2 alpha)-induced contractions. Kainic acid (10(-4)M), an agonist of one subpopulation of central glutamate receptor, potentiated glutamate-induced vasoconstriction; a higher concentration (10(-3)M) produced an irreversible inhibition of glutamate contractility. Only the central glutamate receptor antagonist, ketamine (10(-4)-10(-2)M), induced a reversible, concentration dependent inhibition of glutamate-induced contractions. Glutamate contractility was not dependent on extracellular calcium, an intact endothelium or neuronal function. These results demonstrate a direct effect of glutamate on peripheral arterial tone. Dietary consumption of large quantities of MSG may represent a serious health hazard to certain individuals with pre-existing vascular disease.
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PMID:Vasospasm contributes to monosodium glutamate-induced headache. 226 10

5-Hydroxytryptamine (serotonin) can evoke both contraction and relaxation of vascular smooth muscle. In disease, the constrictor component of the response to the monoamine appears to dominate. 5HT2-serotonergic antagonists favor dilatation, not only because they block the activating effect of serotonin on vascular smooth muscle, but also because they unmask the (endothelium-dependent) relaxation to the monoamine and brake the amplifying effect that it exerts on platelet aggregation. These properties of serotonergic antagonists help to explain their protective effects in vascular disease.
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PMID:Serotonergic antagonists and vascular disease. 228 53

Serotonin (5HT) constricts large arteries in vitro, an effect which seems contrary to 5HT-induced increases in blood flow observed in vivo. We used angiography to assess large artery responses, and blood flow (Q, electromagnetic flowmeter) to assess arteriolar responses to 5HT, norepinephrine (NE), and antagonists in the femoral circulation of the intact, anesthetized dog. 5HT constricted large arteries at a threshold dose of less than 10 micrograms/min, giving a 45 +/- 3% reduction of popliteal artery diameter at 100 micrograms/min (p less than 0.001). NE failed to constrict large arteries. With 100 micrograms/min 5HT, Q increased (delta Q = 108 +/- 26 ml/min; p = 0.001). NE decreased Q. Ketanserin, a 5HT and alpha 1-adrenergic antagonist, exerted a dose-dependent inhibition of 5HT-induced large artery constriction. Methysergide partially blocked the 5HT-induced large artery constriction. Ketanserin potentiated the Q response to 5HT whereas higher doses of methysergide reduced the Q response to 5HT. Neither indomethacin nor propranolol altered either response. Failure of NE to constrict large arteries in vivo and ketanserin antagonism of constriction produced by 5HT suggest the response to 5HT involves the 5HT2 receptor. No role for the 5HT2 receptor in blood flow responses is suggested. These observations may have implications for therapy of occlusive vascular disease.
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PMID:Differential large and small vessel responses to serotonin in the dog hindlimb in vivo: role of the 5HT2 receptor. 258 Jan 49

Endothelial cell (EC) injury and the response of EC and smooth muscle cells (SMCs) to injury contribute to the pathophysiology in patients with vascular disease and atherosclerosis. Since platelets have been suggested to play an important role in modulating vascular injury, the present study was undertaken to examine the influence and mechanism of action of individual platelet factors on bovine aortic EC and SMC migration using an in vitro wound assay system. Serotonin decreased EC proliferation and reduced EC migration 21 +/- 1% (p less than 0.005), which was attenuated by imipramine. Transforming growth factor-beta reduced EC proliferation and decreased EC migration 52 +/- 3% (p less than 0.005). Norepinephrine increased EC proliferation but decreased EC migration 26 +/- 2% (p less than 0.005), which was abolished by phenoxybenzamine. Histamine increased EC proliferation but reduced EC migration 29 +/- 2% (p less than 0.005), which was attenuated by diphenhydramine. Platelet-derived growth factor decreased EC proliferation and decreased EC migration 40 +/- 2% (p less than 0.005). In contrast, serotonin increased SMC proliferation and increased SMC migration 31 +/- 2% (p less than 0.005), which was abolished by ketanserin. Transforming growth factor-beta increased SMC migration 35 +/- 5% (p less than 0.005). Norepinephrine increased SMC proliferation and increased SMC migration 43 +/- 4% (p less than 0.005), which was abolished by propranolol. Histamine increased SMC proliferation and increased SMC migration 38 +/- 3% (p less than 0.005), which was abolished by cimetidine. Platelet-derived growth factor increased SMC proliferation and increased SMC migration 40 +/- 3% (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of platelet factors on migration of cultured bovine aortic endothelial and smooth muscle cells. 279 Dec 19

Infusion of prostacyclin during cardiopulmonary bypass (CPB) reduces platelet activation, diminishes postoperative blood loss and decreases arterial blood pressure. In spite of continuous prostacyclin infusion, there is a delayed gradual rise in arterial pressure and resistance from low initial levels. We measured epinephrine (E), norepinephrine (NE), serotonin (5-HT), angiotensin II (ATII) and arginine-vasopressin (AVP) in plasma and carried out hemodynamic studies in 19 patients operated for coronary vascular disease. Eight patients served as a control group and were subjected to routine CPB. Eleven patients received prostacyclin 50 ng/kg/min during CPB. E and NE increased four- to sixfold during CPB from about 0.5 ng/ml (P less than 0.001). There was no difference between the groups. During CPB AVP increased sixfold from about 20 pg/ml in both groups (P less than 0.001), decreased early after CPB and increased again to high levels 3 h after CPB. The combined action of E, NE and AVP is of likely importance for the rise in systemic vascular resistance and/or need of vasodilation during CPB in the control group. ATII did not increase in the control group, but increased fourfold to about 20 pg/ml (P less than 0.01) during CPB in the prostacyclin group. The addition of AT II to E, NE and AVP seems responsible for the gradual return of arterial pressure and resistance during prostacyclin infusion. Postoperative hypertension and/or need of vasodilation 3 h after CPB was associated with high AVP levels in both groups. Hypotension caused by prostacyclin infusion did not increase E, NE or AVP above levels produced by CPB and moderate hypotension alone.
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PMID:Effects of cardiopulmonary bypass and prostacyclin on plasma catecholamines, angiotensin II and arginine-vasopressin. 388 84

The triptans are 5-HT(1B/1D) agonists used as migraine and cluster-specific agents. Seven are in commercial use worldwide; in order of release these are sumatriptan, zolmitriptan, rizatriptan, naratriptan, almotriptan, frovatriptan and eletriptan. Sumatriptan has been in clinical use since 1991, and although postmarketing studies have stimulated much debate of triptan strengths and weaknesses, their overall safety profile appears excellent. The most serious adverse events are cardiovascular, due to coronary artery narrowing as a consequence of coronary artery 5-HT(1B) receptor activity. Triptans are contraindicated in patients with vascular disease. Other events are even more rare, and include the potential for drug-drug interactions, based on metabolic elimination pathways. Serotonin syndrome has been a concern, but one large prospective study failed to document a single case, and reports are sporadic and not clearly causative.
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PMID:Safety profile of the triptans. 1290 12

Serotonin is released from nerve terminals distributed at the intestinal chromaffin cells, which are taken up into platelets. The serotonin is released at the site where platelets are activated in such situations as atherosclerotic vascular lesions. Therefore, we assumed that the serotonin level could be a suitable marker for atherosclerosis. We developed a new high-performance liquid chromatographic (HPLC) method, including a column-switching system and a post-column reaction with benzylamine, for measurement of serotonin levels in samples from patients with coronary heart disease. The vacuum tubes containing the 3mg/ml (7.4mmol/l) of ethylenediaminetetraacetic acid dipotassium (EDTA2K) were used for collecting the samples of platelet-poor plasma (PPP) because the concentration of anticoagulant in the commercially available vacuum tube containing the 1-2mg/ml (2.5-5.0mmol/l) of EDTA2K was not enough. The serotonin levels in PPP and whole blood of healthy subjects and 4 groups of patients with effort angina pectoris (e-AP), unstable angina (u-AP), old myocardial infarction (OMI), and vasospstic angina pectoris (VSAP), were determined by using the developed method. The serotonin levels in PPP from patients of u-AP, OMI, and VSAP were significantly higher than those of healthy subjects(p<0.001, p<0.005, and p<0.001). The ratio of PPP to whole blood of all disease groups were significantly higher than those of healthy subjects (p<0.001). From these findings, we propose that serotonin is useful as a novel marker for atherosclerotic vascular disease.
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PMID:[Serotonin: a novel marker for atherosclerotic vascular disease]. 1547 25


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