Abnormal neurovascular coupling as a cause of excess cerebral vasodilation in familial migraine.

Abstract:

AIMS:Acute migraine attack in familial hemiplegic migraine type 2 (FHM2) patients is characterized by sequential hypo- and hyperperfusion. FHM2 is associated with mutations in the Na, K-ATPase α2 isoform. Heterozygous mice bearing one of these mutations (α2+/G301R mice) were shown to have elevated cerebrovascular tone and, thus, hypoperfusion that might lead to elevated concentrations of local metabolites. We hypothesize that these α2+/G301R mice also have increased cerebrovascular hyperaemic responses to these local metabolites leading to hyperperfusion in the affected part of the brain. METHODS AND RESULTS:Neurovascular coupling was compared in α2+/G301R and matching wild-type (WT) mice using Laser Speckle Contrast Imaging. In brain slices, parenchymal arteriole diameter and intracellular calcium changes in neuronal tissue, astrocytic endfeet, and smooth muscle cells in response to neuronal excitation were assessed. Wall tension and smooth muscle membrane potential were measured in isolated middle cerebral arteries. Quantitative polymerase chain reaction, western blot, and immunohistochemistry were used to assess the molecular background underlying the functional changes. Whisker stimulation induced larger increase in blood perfusion, i.e. hyperaemic response, of the somatosensory cortex of α2+/G301R than WT mice. Neuronal excitation was associated with larger parenchymal arteriole dilation in brain slices from α2+/G301R than WT mice. These hyperaemic responses in vivo and ex vivo were inhibited by BaCl2, suggesting involvement of inward-rectifying K+ channels (Kir). Relaxation to elevated bath K+ was larger in arteries from α2+/G301R compared to WT mice. This difference was endothelium-dependent. Endothelial Kir2.1 channel expression was higher in arteries from α2+/G301R mice. No sex difference in functional responses and Kir2.1 expression was found. CONCLUSION:This study suggests that an abnormally high cerebrovascular hyperaemic response in α2+/G301R mice is a result of increased endothelial Kir2.1 channel expression. This may be initiated by vasospasm-induced accumulation of local metabolites and underlie the hyperperfusion seen in FHM2 patients during migraine attack.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Staehr C,Rajanathan R,Postnov DD,Hangaard L,Bouzinova EV,Lykke-Hartmann K,Bach FW,Sandow SL,Aalkjaer C,Matchkov VV

doi

10.1093/cvr/cvz306

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

2009-2020

issue

12

eissn

0008-6363

issn

1755-3245

pii

5618722

journal_volume

116

pub_type

杂志文章
  • Enalapril effects on atrial remodeling and atrial fibrillation in experimental congestive heart failure.

    abstract:OBJECTIVE:Atrial remodeling contributes to the maintenance of atrial fibrillation (AF) in several cardiac disorders. There is evidence that angiotensin-converting enzyme (ACE) inhibitors reduce the prevalence of AF in patients with congestive heart failure (CHF). There have been no studies performed to assess the effec...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00243-2

    authors: Shi Y,Li D,Tardif JC,Nattel S

    更新日期:2002-05-01 00:00:00

  • Interleukin 8 and cardiovascular disease.

    abstract::Since the establishment of the inflammatory basis of atherosclerosis, several pro- or anti-inflammatory agents have been examined as potential mediators of the biochemical pathways of lesion formation. Interleukin (IL)-8 was first characterized in 1987. Since then, knowledge regarding its role in leucocyte trafficking...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvp241

    authors: Apostolakis S,Vogiatzi K,Amanatidou V,Spandidos DA

    更新日期:2009-12-01 00:00:00

  • Limitation of myocardial infarct size in the rabbit by ischaemic preconditioning is abolished by sodium 5-hydroxydecanoate.

    abstract:OBJECTIVE:To investigate the effect of the ATP-sensitive potassium (KATP) channel inhibitor sodium 5-hydroxydecanoate (5-HD) on the reduction in myocardial infarct size afforded by ischaemic preconditioning in the sodium pentobarbitone rabbit. METHODS:New Zealand white rabbits were anaesthetised with sodium pentobarbi...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Hide EJ,Thiemermann C

    更新日期:1996-06-01 00:00:00

  • Reverse rate dependency is an intrinsic property of canine cardiac preparations.

    abstract:AIMS:Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD). In spite of the several theories developed so far to explain this reverse rate dependency (RRD), its mechanism has not yet been clarified. The aim of the present work was to further elucidate the mech...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp213

    authors: Bányász T,Horváth B,Virág L,Bárándi L,Szentandrássy N,Harmati G,Magyar J,Marangoni S,Zaza A,Varró A,Nánási PP

    更新日期:2009-11-01 00:00:00

  • Ablation of Nkx2-5 at mid-embryonic stage results in premature lethality and cardiac malformation.

    abstract:AIMS:Human congenital heart disease linked to mutations in the homeobox transcription factor, NKX2-5, is characterized by cardiac anomalies, including atrial and ventricular septal defects as well as conduction and occasional defects in contractility. In the mouse, homozygous germline deletion of Nkx2-5 gene results in...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvr037

    authors: Terada R,Warren S,Lu JT,Chien KR,Wessels A,Kasahara H

    更新日期:2011-07-15 00:00:00

  • Cardiac tissue geometry as a determinant of unidirectional conduction block: assessment of microscopic excitation spread by optical mapping in patterned cell cultures and in a computer model.

    abstract:OBJECTIVE:Unidirectional conduction block (UCB) and reentry may occur as a consequence of an abrupt tissue expansion and a related change in the electrical load. The aim of this study was to evaluate critical dimensions of the tissue necessary for establishing UCB in heart cell culture. METHODS:Neonatal rat heart cell...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Fast VG,Kléber AG

    更新日期:1995-05-01 00:00:00

  • Sympathetic outflow to the hand in patients with Raynaud's phenomenon.

    abstract::Microelectrode recordings of skin nerve sympathetic activity were made in the median nerve supplying the right hand of nine patients with Raynaud's phenomenon and 10 control subjects. With subjects warmed up (finger temperature 33 to 34 degrees C) different manoeuvres were used to evoke strong, single sympathetic burs...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/19.5.249

    authors: Fagius J,Blumberg H

    更新日期:1985-05-01 00:00:00

  • Activin-like kinase receptor 1 (ALK1) in atherosclerotic lesions and vascular mesenchymal cells.

    abstract:OBJECTIVE:Activin-like kinase receptor 1 (ALK1) is a transforming growth factor (TGF)-beta type I receptor expressed in vascular mesenchyme, yet its function in vascular mesenchymal cells (VMC) is unclear. We examined ALK1 expression in human coronary atherosclerotic lesions and bovine and human VMC undergoing cellular...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2006.09.014

    authors: Yao Y,Zebboudj AF,Torres A,Shao E,Boström K

    更新日期:2007-05-01 00:00:00

  • Baroreflex sensitivity in conscious rats: the influence of recording site.

    abstract::Arterial blood pressures were measured simultaneously in the thoracic and abdominal aortas in the same conscious rats. Intravenous administration of sodium nitroprusside caused a greater fall in systolic blood pressure in the abdominal aorta than in the thoracic aorta, whereas intravenous administration of methoxamine...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/20.5.379

    authors: Gardiner SM,Bennett T

    更新日期:1986-05-01 00:00:00

  • Contraction in cardiac endothelial cells contributes to changes in capillary dimensions following ischaemia and reperfusion.

    abstract:OBJECTIVE:Ischaemia followed by reperfusion brings about a reduction in cardiac capillary cross-sectional dimensions which is consistent with constriction. The aim of this study was to test the hypothesis that the reduction in cardiac capillary dimensions that occurs in ischaemia and reperfusion is caused by endothelia...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00173-5

    authors: Glyn MC,Ward BJ

    更新日期:2000-11-01 00:00:00

  • Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation.

    abstract::The cardiac SR Ca(2+)-ATPase (SERCA2a) regulates intracellular Ca(2+)-handling and thus, plays a crucial role in initiating cardiac contraction and relaxation. SERCA2a may be modulated through its accessory phosphoprotein phospholamban or by direct phosphorylation through Ca(2+)/calmodulin dependent protein kinase II ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(02)00694-6

    authors: Frank KF,Bölck B,Erdmann E,Schwinger RH

    更新日期:2003-01-01 00:00:00

  • NO contributes to EDHF-like responses in rat small arteries: a role for NO stores.

    abstract:OBJECTIVES:Responses to EDHF are usually characterised in the presence of nitric oxide synthase (NOS) and cyclooxygenase (COX) inhibitors. The contribution of NO to endothelium-dependent relaxation in the presence of NOS inhibitors was assessed using NO scavengers with the objective of testing (i) whether any residual ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00611-9

    authors: Chauhan S,Rahman A,Nilsson H,Clapp L,MacAllister R,Ahluwalia A

    更新日期:2003-01-01 00:00:00

  • Beta-adrenoceptor function changes with age of subject in myocytes from non-failing human ventricle.

    abstract::The contractile response to beta-adrenoceptor stimulation has been found to be reduced in single myocytes from failing human ventricle. A portion of that reduction was statistically related to the age of the patient. We have developed a method for obtaining viable contracting myocytes from small biopsies of human vent...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:

    authors: Davies CH,Ferrara N,Harding SE

    更新日期:1996-01-01 00:00:00

  • Influence of ivabradine on reverse remodelling during mechanical unloading.

    abstract:AIMS:Ivabradine (Iva) has shown beneficial structural and functional effects in clinical and experimental heart failure (HF), but its action in combination with mechanical unloading (MU), such as during treatment with left ventricular assist devices (LVAD), is unknown. The aim of this study was to investigate the effec...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvs318

    authors: Navaratnarajah M,Ibrahim M,Siedlecka U,van Doorn C,Shah A,Gandhi A,Dias P,Sarathchandra P,Yacoub MH,Terracciano CM

    更新日期:2013-02-01 00:00:00

  • Serotonin receptor blockade improves distal perfusion after lower limb ischemia in the fatty Zucker rat.

    abstract:OBJECTIVE:Lower limb perfusion following arterial occlusion depends on the recruitment of collateral vessels. Blood flow through these collateral vessels may be jeopardized by hypersensitivity to vasoconstriction by serotonin (5-HT), as has been reported during hyperlipidemia and diabetes. Therefore the aim of this stu...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00538-2

    authors: Janiak P,Lainée P,Grataloup Y,Luyt CE,Bidouard JP,Michel JB,O'Connor SE,Herbert JM

    更新日期:2002-11-01 00:00:00

  • Changes in regional myocardial blood flow and variable development of hypertrophy after aortic banding in puppies.

    abstract::Supravalvar aortic banding was performed in 6 to 12 week puppies. Sixteen animals were studied 7.3 (3.5 to 10) months later, closed-chested under morphine-chloralose, catheters being positioned in the great vessels and heart, including the left atrium for microsphere injection. Compared with 11 controls, eight dogs de...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/15.12.711

    authors: Einzig S,Leonard JJ,Tripp MR,Lucas RV,Swayze CR,Fox IJ

    更新日期:1981-12-01 00:00:00

  • Physiological and pathophysiological roles of eicosanoids in the microcirculation.

    abstract::Eicosanoids are important mediators of both physiological and pathophysiological responses of the microcirculation. These biologically active lipid mediators can be produced locally by the cellular elements within the microvasculature (endothelium, pericytes, smooth muscle cells) as well as interstitial cells (e.g. fi...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:

    authors: Gerritsen ME

    更新日期:1996-10-01 00:00:00

  • Matrix metalloproteinase-2 and myocardial oxidative stress injury: beyond the matrix.

    abstract::Matrix metalloproteinase (MMP)-2 belongs to a family of zinc-dependent proteases which are best known for their ability to proteolyse extracellular matrix proteins throughout the body, including the cardiovascular system. Increased MMP-2 activity has been demonstrated in myocardial ischaemia and reperfusion injury and...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvp268

    authors: Kandasamy AD,Chow AK,Ali MA,Schulz R

    更新日期:2010-02-01 00:00:00

  • Separation of the oscillatory current from other currents in cardiac Purkinje fibres.

    abstract::An oscillatory current (Ios) can be recorded after depolarising clamps of a given amplitude and duration. To determine whether Ios depends on other currents activated during the clamp, the Ios was investigated in the absence and in the presence of 4-aminopyridine (4-AP) and cesium (Cs). The following results were obta...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/16.11.637

    authors: Mugelli A

    更新日期:1982-11-01 00:00:00

  • Changes in pulmonary vein flow pattern during volume loading.

    abstract:OBJECTIVE:The aim was to investigate the effect of increased left ventricular filling pressure on the pulmonary vein flow (PVQ) pattern. METHODS:Pulmonary vein flow was recorded using an ultrasonic transit time flow meter in six anaesthetised dogs. Mean left atrial pressure was increased by stepwise volume loading fro...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/27.3.411

    authors: Smiseth OA,Lødemel K,Riddervold F,Blaha M

    更新日期:1993-03-01 00:00:00

  • MicroRNAs and atrial fibrillation: new fundamentals.

    abstract::Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia associated with pronounced morbidity, mortality, and socio-economic burden. This pathological entity is associated with an altered expression profile of genes that are important for atrial function. MicroRNAs (miRNAs), a new class of non-cod...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvq350

    authors: Wang Z,Lu Y,Yang B

    更新日期:2011-03-01 00:00:00

  • Signal transduction in spontaneous myogenic tone in isolated arterioles from rat skeletal muscle.

    abstract:OBJECTIVE:The mechanism of spontaneous myogenic tone was investigated in isolated arteriolar segments. METHODS:Arterioles were isolated from rat cremaster muscle. Segments were endothelium-denuded and mounted in a pressure myograph at 75 mmHg. Under this condition, segments spontaneously constricted from a passive dia...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(98)00161-8

    authors: Bakker EN,Kerkhof CJ,Sipkema P

    更新日期:1999-01-01 00:00:00

  • Prevention of VEGF-mediated microvascular permeability by C-peptide in diabetic mice.

    abstract:AIMS:Human C-peptide has a beneficial effect on the prevention of diabetic neuropathy, nephropathy, and vascular complications; however, its role in protection against increased vascular permeability in diabetes remains unclear. Our purpose was to explore the potential protective role of C-peptide against microvascular...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvt238

    authors: Lim YC,Bhatt MP,Kwon MH,Park D,Lee S,Choe J,Hwang J,Kim YM,Ha KS

    更新日期:2014-01-01 00:00:00

  • The class III antiarrhythmic drugs dofetilide and sotalol prevent AF induction by atrial premature complexes at doses that fail to terminate AF.

    abstract:BACKGROUND:Clinical trials suggest that sotalol and dofetilide are much more effective in preventing atrial fibrillation (AF) than in terminating it. This study evaluated potential mechanisms of discordant sotalol and dofetilide effects on AF termination vs. prevention. METHODS:We applied 240-electrode epicardial mapp...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00320-5

    authors: Derakhchan K,Villemaire C,Talajic M,Nattel S

    更新日期:2001-04-01 00:00:00

  • Connexin 30 is expressed in the mouse sino-atrial node and modulates heart rate.

    abstract:AIMS:This study aimed at characterizing expression and the functional role of the Gjb6 gene, encoding for connexin 30 (Cx30) protein, in the adult mouse heart. METHODS AND RESULTS:The expression of the Gjb6 gene in the mouse heart was investigated by RT-PCR and sequencing of amplified cDNA fragments. The sites of Gjb6...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp280

    authors: Gros D,Théveniau-Ruissy M,Bernard M,Calmels T,Kober F,Söhl G,Willecke K,Nargeot J,Jongsma HJ,Mangoni ME

    更新日期:2010-01-01 00:00:00

  • Effect of adenosine therapy at reperfusion on myocardial infarct size in dogs.

    abstract:OBJECTIVES:The concept of lethal reperfusion injury in ischemic myocardium has been the subject of controversy. Adenosine administered during reperfusion has been reported to limit lethal reperfusion injury in several studies. On the contrary, it has been reported that cardioprotection may not be achieved with adenosin...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/0008-6363(95)00235-9

    authors: Vander Heide RS,Reimer KA

    更新日期:1996-05-01 00:00:00

  • Angiotensin II enhances carotid body chemoreflex control of sympathetic outflow in chronic heart failure rabbits.

    abstract:OBJECTIVES:We investigated whether Angiotensin II (Ang II) modulates peripheral chemoreflex function through carotid body (CB) chemoreceptors in chronic heart failure (CHF). METHODS:We measured renal sympathetic nerve activity (RSNA) in response to graded hypoxia before and after intravenous administration of Ang II (...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2006.03.017

    authors: Li YL,Xia XH,Zheng H,Gao L,Li YF,Liu D,Patel KP,Wang W,Schultz HD

    更新日期:2006-07-01 00:00:00

  • Cardiovascular and sympathetic responses to ouabain injected into the hypothalamus in rats.

    abstract::To investigate the effects of sodium-potassium activated adenosine triphosphatase inhibition on central cardiovascular regulation a microinjection of ouabain was given into the hypothalamus of urethane anaesthetised rats. Doses of 0.01-1.0 micrograms per rat injected into the posterior hypothalamus produced a rise in ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/20.4.294

    authors: Iyoda I,Takahashi H,Lee LC,Okajima H,Inoue A,Sasaki S,Takeda K,Yoshimura M,Ijichi H

    更新日期:1986-04-01 00:00:00

  • Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade.

    abstract:OBJECTIVE:Ischemic postconditioning protects the reperfused heart from infarction, and this protection is dependent on the occupancy of adenosine receptors. We further explored the role of adenosine receptors in this salvage. METHODS:In situ rabbit hearts underwent 30 min of regional ischemia and 3 h of reperfusion, a...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2006.02.014

    authors: Philipp S,Yang XM,Cui L,Davis AM,Downey JM,Cohen MV

    更新日期:2006-05-01 00:00:00

  • Noninvasive determination of the mitral valve area in stenosis: a computational model and correlation with autopsy and open heart measurements.

    abstract::An analytical formulation has been developed which allows the computation of mitral valve area (A) from the potentially noninvasive paramaeters of hear rate (R), cardiac output (CO) and diastolic filling period (DFP) by the equation A = 21 CO/R x DFP2. The computed areas correlate with autopsy and open heart measureme...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/14.4.223

    authors: Seitz WS,Operschall EJ

    更新日期:1980-04-01 00:00:00