Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasoactive factors produced and released by the endothelium exert a powerful influence on vascular tone in the cerebral circulation. Impaired endothelium-dependent responses, such as decreased production of endothelium-derived relaxing factors, and/or release of endothelium-derived contractile factors may give rise to different pathophysiological conditions. Among the endothelium-derived contractile factors the endothelins have recently received particular attention. Endothelin-1 is the major isoform in the endothelin family, which also includes endothelin-2 and endothelin-3. Endothelin-1 is synthesized within the endothelium of cerebral vessels, whereas both endothelin-1 and endothelin-3 in addition have been identified in neurons and glia. Recent electrophysiological work has suggested a neuromodulatory role for these peptides, but at present the general interest is mainly focused on their vasoactive role. Physiological stimuli such as hypoxia, anoxia, and hemodynamic shear stress will stimulate the endothelial endothelin production. In the brain, at least two types of specific subreceptors have been cloned; ETA receptors, exclusively associated with blood vessels and ETB receptors also found on glial, epithelial, and ependymal cells. The endothelins seem so far to be the most potent vasoconstrictors yet identified. The circulating plasma levels of immunoreactive endothelin are low. Since more than 80% of the total amount released from endothelial cells seems to be secreted towards the underlying smooth muscle, endothelins have been ascribed a local vasoregulatory role. Endothelins are believed to be involved in several of our most common cerebrovascular diseases and the present review comments on their possible pathophysiological role in subarachnoid haemorrhage, cerebral ischemia, and migraine.
Cephalalgia 1994 Aug
PMID:Endothelins: a role in cerebrovascular disease? 795 53

The role of vascular phenomena taking place during an attack of migraine are poorly understood. The aim of this study was to measure systemic levels of nitric oxide and endothelin-1, two of the most potent vasoactive mediators known, and to assess vasomotor responses through transcranial Doppler ultrasound monitoring in patients suffering from migraine without aura, both during the headache event and in headache-free periods as well as after pharmacologically induced pain relief. Seven patients (mean age 31.3 years, range 24 to 49 years), five women and two men, were enrolled in the pilot study. Transcranial Doppler recordings were performed according to conventional procedure. Endothelin-1 concentrations were measured by means of radioimmunoassay, whereas nitric oxide levels were estimated using electron paramagnetic resonance spectroscopy. Ultrasound evaluation did not show significant changes during migraine attacks compared to the interictal condition. Nitric oxide levels showed only slight differences between basal and attack conditions (0.85 +/- 0.46 versus 1.56 +/- 0.88, expressed as arbitrary units), and were raised after pharmacological intervention (2.91 +/- 1.93, P < 0.05). Plasma endothelin-1 concentrations decreased during migraine attacks with respect to interictal conditions (3.99 +/- 1.21 pg/mL versus 4.23 +/- 1.19), and returned to basal values (4.44 +/- 1.08 pg/mL) after relief of pain. Coupling the measurements of systemic levels of nitric oxide and endothelin-1 with transcranial Doppler velocity results will provide useful information on the hemodynamic changes of cerebral blood flow regulation in migraineurs, thereby adding new insights into the mechanisms of the migraine attack.
Headache 1996 May
PMID:Nitric oxide, endothelin-1, and transcranial Doppler in migraine. Findings in interictal conditions and during migraine attack. 868 72

Endothelin-1 (ET-1) exerts powerful vasoconstrictive and blood pressure elevating properties through endothelial cells. However, no systematic examination of ET-1 in migraine has ever been attempted. The present investigation was focused on evaluating the level of ET-1 in patients with migraine with aura. Studies on ET-1 were made in 17 patients with migraine with aura (age, 23.4 +/- 9.1 years old, mean +/- SD) according to the Classification of Headache of the Ad Hoc Committee. All patients had been free of migraine attacks for at least 7 days prior to the examination. Twenty-eight age-matched healthy volunteers (age, 23.0 +/- 12.3 years old) were similarly used as a control group. None of them revealed evidence of any other disease, such as hypertension, obesity, or heart disease. Informed consent was obtained from each subject. We measured the immunoreactive ET-1 in plasma by radioimmunoassay. The plasma level of ET-1 in migraine was 2.53 +/- 1.06 pg/ml. On the other hand, the level of ET-1 in the controls was 4.24 +/- 0.80 pg/ml. The ET-1 level in migraine was significantly lower than that in the controls (p < 0.002). We also measured the level of ET-1 in the cerebrospinal fluid (CSF). There was no significant difference between migraine (23.2 +/- 3.10 pg/ml) and the control group (20.85 +/- 3.20 pg/ml). In conclusion, the lower plasma level of ET-1 observed in the patients with migraine is consistent with the pathogenesis of migraine, further supporting the hypothesis that a lower ET-1 may be closely related to marked vasodilatation following constriction partly due to a deficiency of ET-1 for maintaining vasoconstriction.
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PMID:[Lower level of endothelin-1 in migraine with aura]. 872 Mar 38

The purpose of this study was to investigate the tolerability, pharmacokinetics, and pharmacodynamics of ascending doses of tezosentan, an IV dual endothelin receptor antagonist, during first administration in humans. Tezosentan infused at doses of 5, 20, 50, 100, 200, 400, and 600 mg for 1 h was administered to sequential groups of six male subjects in a randomized, placebo-controlled, double-blind design. Recording of vital signs, electrocardiogram, adverse events, and clinical laboratory parameters monitored tolerability and safety. Blood samples were collected frequently for pharmacokinetic determinations and measurement of plasma endothelin-1 concentrations. Tezosentan was well tolerated at all dose levels. Headache was the most frequently reported adverse event and occurred at a higher incidence than with placebo at doses of > or = 100 mg. No clinically relevant changes in vital signs, electrocardiographic, or clinical laboratory parameters occurred. Plasma concentrations of tezosentan rapidly approached steady state and could be described by a two-compartment model. The volume of distribution at steady state (approximately 16 l) and the clearance (approximately 30 l/h) were considered independent of dose, in view of the wide dose range explored. A pronounced and rapid disposition phase (half-life 6 min), accounting for the major part of the elimination, was followed by a slower phase (half-life 3 h), probably caused by distribution from tissues. Endothelin-1 concentrations increased in a dose- and concentration-dependent fashion and returned slowly to baseline after termination of the infusion. Tezosentan warrants further clinical development in view of its tolerability and pharmacokinetic profile, which appears advantageous for application in emergency situations.
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PMID:Entry-into-humans study with tezosentan, an intravenous dual endothelin receptor antagonist. 1202 73