| 281. |
- Passant, Ulla, et al.
(författare)
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Cortical blood flow during head-up postural change in subjects with orthostatic hypotension
- 1993
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Ingår i: Clinical autonomic research : official journal of the Clinical Autonomic Research Society. ; 3:5, s. 311-8
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Tidskriftsartikel (refereegranskat)abstract
- Regional cerebral blood flow was measured with the 133-Xenon inhalation method in seven healthy subjects with orthostatic hypotension not due to autonomic failure (i.e. non-neurogenic clinical disorder). Measurements were performed during supine rest and during head-up tilt (70 degrees). All subjects had a consistent drop in systolic blood pressure and the typical symptomatology of orthostatic hypotension. The results showed lower mean hemispheric blood flow during head-up tilt than during supine rest. In addition, a consistent and significant redistribution of the regional flow values was seen, with a reduction in frontal and an increase in postcentral areas. The frontal flow decrease during tilt was more marked than in subjects without orthostatic hypotension and was not related to variations in the level of PCO2 or to respiration. In contrast to the clinical symptoms of orthostatic hypotension (dizziness, nausea, visual disturbances, and in some cases syncope), the cortical blood flow reduction was, however, relatively moderate.
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| 282. |
- Passant, Ulla, et al.
(författare)
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Orthostatic hypotension in organic dementia: relationship between blood pressure, cortical blood flow and symptoms
- 1996
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Ingår i: Clinical autonomic research : official journal of the Clinical Autonomic Research Society. ; 6:1, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- Regional cerebral blood flow was measured in 35 patients with organic dementia (Alzheimer's disease, n = 13, vascular dementia, n = 17, frontotemporal dementia, n = 5) and orthostatic hypotension. Measurements were performed during supine rest and during head-up tilt (60 degrees). Despite marked blood pressure falls, few patients had symptoms of orthostatic hypotension. All three dementia groups had a decrease in regional cerebral blood flow in the frontal lobes during head-up tilt, but no change in mean hemispheric flow. All patients had a consistent drop in their systolic blood pressure upon head-up tilt, with a wide variation over time. The findings suggest that orthostatic hypotension needs to be considered, and actively sought for, in organic dementia as many patients may lack the typical symptoms of orthostatic hypotension, despite a marked fall in blood pressure.
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| 283. |
- Petersen, KA, et al.
(författare)
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Presence and function of the calcitonin gene-related peptide receptor on rat pial arteries investigated in vitro and in vivo
- 2005
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 25:6, s. 424-432
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Tidskriftsartikel (refereegranskat)abstract
- Calcitonin gene-related peptide (CGRP) and related peptides may be involved in migraine pathogenesis. To understand their vasomotor role in the cerebral circulation, we performed two studies, a pressurized arteriography study of the middle cerebral artery (MCA) and a genuine closed cranial window (gCCW) in vivo study. Using the pressurized arteriography model rat MCAs were mounted on micropipettes, pressurized to 85 mmHg and luminally perfused. The diameter responses to luminally and abluminally applied rat-alpha CGRP, rat-beta CGRP, amylin and adrenomedullin were compared with the resting diameter. Only abluminally applied CGRP induced dilation of the cerebral arteries; E-max for alpha CGRP and beta CGRP were 35 +/- 0.5% and 10.8 +/- 0.2%. These responses were blocked by CGRP(8-37). The gCCW model allowed videomicroscopic visualization of the pial vessels in anaesthetized rats. Changes in vessel diameter to intravenously administered alpha CGRP and beta CGRP were compared with pre-infusion baseline. Intravenous infusion of alpha CGRP and beta CGRP in the highest dose induced dilation of the cerebral cortical pial arteries/arterioles of 40.3 +/- 7.5% and 49.1 +/- 8.4%, respectively. However, this was probably secondary to a decrease in blood pressure of 44.8 +/- 3.3 mmHg and 49.2 +/- 3.3 mmHg. Our results suggest that CGRP receptors are probably functional on the smooth muscle cells and not on the endothelium of rat cerebral arteries.
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| 284. |
- Ploug, Kenneth Beri, et al.
(författare)
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Pharmacological and molecular comparison of K-ATP channels in rat basilar and middle cerebral arteries
- 2006
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 553:1-3, s. 254-262
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Tidskriftsartikel (refereegranskat)abstract
- ATP-sensitive potassium (K-ATP) channels play an important role in the regulation of cerebral vascular tone. In vitro studies using synthetic K-ATP channel openers suggest that the pharmacological profiles differ between rat basilar arteries and rat middle cerebral arteries. To address this issue, we studied the possible involvement of endothelial K-ATP channels by pressurized arteriography after luminal administration of synthetic K-ATP channel openers to rat basilar and middle cerebral arteries. Furthermore, we examined the mRNA and protein expression profile of K-ATP channels to rat basilar and middle cerebral arteries using quantitative real-time PCR (Polymerase Chain Reaction) and Western blotting, respectively. In the per-fusion system, we found no significant responses after luminal application of three K-ATP channel openers to rat basilar and middle cerebral arteries. In contrast, abluminal application caused a concentration-dependent dilatation of both arteries, that was more potent in basilar than in middle cerebral arteries. Quantitative real-time PCR detected the presence of mRNA transcripts of the K-ATP channel subunits Kir6.1, Kir6.2, SUR1 and SLTR2B, while SUR2A mRNA was barely detected in both rat basilar and middle cerebral arteries. Of the five mRNAs, the expression levels of Kir6.1 and SUR2B transcripts were predominant in both rat basilar and middle cerebral arteries. Western blotting detected the presence of Kir6.1, Kir6.2, SUR1 and SUR2B proteins in both arteries. Densitometric measurements of the Western blot signals further showed higher expression levels of Kir6.1 and SUR2B proteins in rat middle cerebral arteries than was found in rat basilar arteries. In conclusion, our in vitro pharmacological studies showed no evidence for functional endothelial K-ATP channels in either artery. Furthermore, the results indicate that Kir6.1/SUR2B is the major K-ATP channel complex in rat basilar and middle cerebral arteries.
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| 285. |
- Povlsen, Gro Klitgaard, et al.
(författare)
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In vivo experimental stroke and in vitro organ culture induce similar changes in vasoconstrictor receptors and intracellular calcium handling in rat cerebral arteries
- 2012
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 219:4, s. 507-520
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral arteries subjected to different types of experimental stroke upregulate their expression of certain G-protein-coupled vasoconstrictor receptors, a phenomenon that worsens the ischemic brain damage. Upregulation of contractile endothelin B (ETB) and 5-hydroxytryptamine 1B (5-HT1B) receptors has been demonstrated after subarachnoid hemorrhage and global ischemic stroke, but the situation is less clear after focal ischemic stroke. Changes in smooth muscle calcium handling have been implicated in different vascular diseases but have not hitherto been investigated in cerebral arteries after stroke. Here, we evaluate changes of ETB and 5-HT1B receptors, intracellular calcium levels, and calcium channel expression in rat middle cerebral artery (MCA) after focal cerebral ischemia and in vitro organ culture, a proposed model of vasoconstrictor receptor changes after stroke. Rats were subjected to 2 h MCA occlusion followed by reperfusion for 1 or 24 h. Alternatively, MCAs from na < ve rats were cultured for 1 or 24 h. ETB and 5-HT1B receptor-mediated contractions were evaluated by wire myography. Receptor and channel expressions were measured by real-time PCR and immunohistochemistry. Intracellular calcium was measured by FURA-2. Expression and contractile functions of ETB and 5-HT1B receptors were strongly upregulated and slightly downregulated, respectively, 24 h after experimental stroke or organ culture. ETB receptor-mediated contraction was mediated by calcium from intracellular and extracellular sources, whereas 5-HT1B receptor-mediated contraction was solely dependent on extracellular calcium. Organ culture and stroke increased basal intracellular calcium levels in MCA smooth muscle cells and decreased the expression of inositol triphosphate receptor and transient receptor potential canonical calcium channels, but not voltage-operated calcium channels.
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| 286. |
- Povlsen, Gro K, et al.
(författare)
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MEK1/2 inhibitor U0126 but not endothelin receptor antagonist clazosentan reduces upregulation of cerebrovascular contractile receptors and delayed cerebral ischemia, and improves outcome after subarachnoid hemorrhage in rats.
- 2015
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016 .- 0271-678X. ; 35:2, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral vasospasm and late cerebral ischemia (LCI) remain leading causes of mortality in patients experiencing a subarachnoid hemorrhage (SAH). This occurs typically 3 to 4 days after the initial bleeding and peaks at 5 to 7 days. The underlying pathophysiology is still poorly understood. Because SAH is associated with elevated levels of endothelin-1 (ET-1), focus has been on counteracting endothelin receptor activation with receptor antagonists like clazosentan, however, with poor outcome in clinical trials. We hypothesize that inhibition of intracellular transcription signaling will be an effective approach to prevent LCI. Here, we compare the effects of clazosentan versus the MEK1/2 blocker U0126 in a rat model of SAH. Although clazosentan directly inhibits the contractile responses in vivo to ET-1, it did not prevent SAH-induced upregulation of ET receptors in cerebral arteries and did not show a beneficial effect on neurologic outcome. U0126 had no vasomotor effect by itself but counteracts SAH-induced receptor upregulation in cerebral arteries and improved outcome after SAH. We suggest that because SAH induces elevated expression of several contractile receptor subtypes, it is not sufficient to block only one of these (ET receptors) but inhibition of transcriptional MEK1/2-mediated upregulation of several contractile receptors may be a viable way towards alleviating LCI.Journal of Cerebral Blood Flow & Metabolism advance online publication, 19 November 2014; doi:10.1038/jcbfm.2014.205.
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| 287. |
- Radziwon-Balicka, Aneta, et al.
(författare)
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A novel multicolor flow-cytometry application for quantitative detection of receptors on vascular smooth muscle cells
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- There is a need to develop new techniques for quantitative measurement of receptors expression on particular vasculature cells types. Here, we describe and demonstrate a novel method to measure quantitatively and simultaneously the expression of endothelin B receptor (ETB) on vascular smooth muscle cells (VSMC). We isolated cells from male rat tissues such as: brain pial, brain intraparenchymal and retina vessels. To analyze solid tissues, a single-cell suspension was prepared by a combined mechanic and enzymatic process. The cells were stained with Fixable Viability Dye, followed by fixation, permeabilization and antibodies staining. The expression of ETB receptors on VSMC was measured by flow-cytometry and visualized by fluorescence microscopy. We obtained a high percentage of viable cells 87.6% ± 1.5% pial; 84.6% ± 4.3% parenchymal and 90.6% ± 4% retina after isolation of single cells. We performed a quantitative measurement of ETB receptor expression on VSMC and we identified two subpopulations of VSMC based on their expression of smooth muscle cells marker SM22α. The results obtained from pial vessels are statistically significant (38.4% ± 4% vs 9.8% ± 3.32%) between the two subpopulations of VSMC. The results obtained from intraparenchymal and retina vessels were not statistically significant. By specific gating on two subpopulations, we were able to quantify the expression of ETB receptors. The two subpopulation expressed the same level of ETB receptor (p = 0.45; p = 0.3; p = 0.42) in pial, parenchymal and retina vessels, respectively. We applied our method to the animals after induction of subarachnoid hemorrhage (SAH). There was statistically significant expression of ETB receptor (p = 0.02) on VSMC between sham 61.4% ± 4% and SAH 77.4% ± 4% rats pial vessels. The presented technique is able to quantitatively and selectively measure the level of protein expression on VSMC. The entire technique is optimized for rat tissue; however the protocol can also be adapted for other species.
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| 288. |
- Rapoport, Alan M., et al.
(författare)
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Some aspects on the pathophysiology of migraine and a review of device therapies for migraine and cluster headache
- 2019
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Ingår i: Neurological Sciences. - : Springer Science and Business Media LLC. - 1590-1874 .- 1590-3478. ; 40:S1, s. 75-80
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Forskningsöversikt (refereegranskat)abstract
- Migraine is a common, severe disease, affecting the brain and blood vessels, causing much pain, time missed from work and family, and severe disability. It affects approximately 12% of most Western populations studied and affects women three times more than men. Cluster headache is a much less common dysfunction of the hypothalamus, involving the sphenopalatine ganglion and other areas; it causes more frequent, shorter, and even more intense pain than migraine. The pain usually comes in cycles and is associated with ipsilateral autonomic features and associated with irritability and inability to stay still. It affects less than 0.1% of the population and is slightly more prevalent in men than women. Although we have some acute care and preventive medications for both types of headache, no treatment is optimal for each patient and some will not respond well or have significant adverse events to existing therapies.
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| 289. |
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| 290. |
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