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Christian Aalkjaer - One of the best experts on this subject based on the ideXlab platform.
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Vasomotion what is currently thought
Acta Physiologica, 2011Co-Authors: Christian Aalkjaer, Donna Briggs Boedtkjer, Vladimir V. MatchkovAbstract:This minireview discusses Vasomotion, which is the oscillation in tone of blood vessels leading to flowmotion. We will briefly discuss the prevalence of Vasomotion and its potential physiological and pathophysiological relevance. We will also discuss the models that have been suggested to explain how a coordinated oscillatory activity of the smooth muscle tone can occur and emphasize the role of the endothelium, the handling of intracellular Ca(2+) and the role of smooth muscle cell ion conductances. It is concluded that Vasomotion is likely to enhance tissue dialysis, although this concept still requires more experimental verification, and that an understanding at the molecular level for the pathways leading to Vasomotion is beginning to emerge.
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Vasomotion – what is currently thought?
Acta physiologica (Oxford England), 2011Co-Authors: Christian Aalkjaer, Donna Briggs Boedtkjer, Vladimir V. MatchkovAbstract:This minireview discusses Vasomotion, which is the oscillation in tone of blood vessels leading to flowmotion. We will briefly discuss the prevalence of Vasomotion and its potential physiological and pathophysiological relevance. We will also discuss the models that have been suggested to explain how a coordinated oscillatory activity of the smooth muscle tone can occur and emphasize the role of the endothelium, the handling of intracellular Ca(2+) and the role of smooth muscle cell ion conductances. It is concluded that Vasomotion is likely to enhance tissue dialysis, although this concept still requires more experimental verification, and that an understanding at the molecular level for the pathways leading to Vasomotion is beginning to emerge.
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BESTROPHIN IS IMPORTANT FOR THE RHYTHMIC BUT NOT THE TONIC CONTRACTION IN RAT MESENTERIC SMALL ARTERIES
Cardiovascular Research, 2011Co-Authors: Torbjoern Broegger, Jens Christian Brings Jacobsen, Vibeke Secher Dam, Donna Briggs Boedtkjer, Henrik Kold-petersen, Finn Skou Pedersen, Christian Aalkjaer, Vladimir V. MatchkovAbstract:Aims We have previously characterized a cGMP-dependent Ca2+-activated Cl– current in vascular smooth muscle cells (SMCs) and have shown its dependence on bestrophin-3 expression. We hypothesize that this current is important for synchronization of SMCs in the vascular wall. In the present study, we aimed to test this hypothesis by transfecting rat mesenteric small arteries in vivo with siRNA specifically targeting bestrophin-3. Methods and results The arteries were tested 3 days after transfection in vitro for isometric force development and for intracellular Ca2+ in SMCs. Bestrophin-3 expression was significantly reduced compared with arteries transfected with mutated siRNA. mRNA levels for bestrophin-1 and -2 were also significantly reduced by bestrophin-3 down-regulation. This is suggested to be secondary to specific bestrophin-3 down-regulation since siRNAs targeting different exons of the bestrophin-3 gene had identical effects on bestrophin-1 and -2 expression. The transfection affected neither the maximal contractile response nor the sensitivity to norepinephrine and arginine-vasopressin. The amplitude of agonist-induced Vasomotion was significantly reduced in arteries down-regulated for bestrophins compared with controls, and asynchronous Ca2+ waves appeared in the SMCs. The average frequency of Vasomotion was not different. 8Br-cGMP restored Vasomotion in arteries where the endothelium was removed, but oscillation amplitude was still significantly less in bestrophin-down-regulated arteries. Thus, Vasomotion properties were consistent with those previously characterized for rat mesenteric small arteries. Data from our mathematical model are consistent with the experimental results. Conclusion This study demonstrates the importance of bestrophins for synchronization of SMCs and strongly supports our hypothesis for generation of Vasomotion.
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Vasomotion has chloride-dependency in rat mesenteric small arteries
Pflugers Archiv : European journal of physiology, 2008Co-Authors: Donna Briggs Boedtkjer, Vladimir V. Matchkov, Ebbe Boedtkjer, Holger Nilsson, Christian AalkjaerAbstract:The possibility that Ca2+-activated Cl− conductances (CaCCs) contribute to oscillations in vascular tone (Vasomotion) is tested in isolated mesenteric small arteries from rats where cGMP independent (ICl(Ca)) and cGMP-dependent (ICl(Ca,cGMP)) chloride conductances are important. The effect of anion substitution and Cl− channel blockers on noradrenaline (NA)-stimulated tension in isometrically mounted mesenteric arteries and for chloride conductance of smooth muscle cells isolated from these arteries were assessed electrophysiologically. Cl−o replacement with aspartate blocked Vasomotion while 36mM SCN−o (substituted for Cl−) was sufficient to inhibit Vasomotion. Oscillations in tone, membrane potential, and [Ca2+]i disappeared with 36mM SCN−. DIDS and Zn2+ blocked ICl(Ca,cGMP) but not ICl(Ca). Vasomotion was not sensitive to DIDS and Zn2+, and DIDS and Zn2+ induce Vasomotion in arteries without endothelium. The Vasomotion in the presence of DIDS and Zn2+ was sensitive to 36mM SCN−o. The anion substitution data indicate that Cl− is crucial for the Vm and [Ca2+]i oscillations underlying Vasomotion. The Cl− channel blocker data are consistent with both CaCCs being important.
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Effect of cyclic guanosine-monophosphate on porcine retinal Vasomotion.
Acta ophthalmologica Scandinavica, 2006Co-Authors: Anders Hessellund, Christian Aalkjaer, Toke BekAbstract:. Purpose: Vasomotion refers to periodic oscillations in vascular tone that ensure the intermittent supply of blood to adjacent microvascular units. Previous evidence from vessels outside the eye suggests that cyclic guanosine-monophosphate (cGMP) is involved in the regulation of Vasomotion, but it is unknown whether this compound has an effect on Vasomotion in retinal vessels. Methods: Retinal arterioles from porcine eyes were studied in a wire myograph. After initiation of Vasomotion, the vessels were stimulated with increasing concentrations of the cGMP agonist 8-Br-cGMP (n = 6), the phosphodiesterase inhibitor zaprinast (n = 6) and the cGMP synthesis inhibitor L-NAME (n = 6). High concentrations of L-NAME blocked Vasomotion, and control experiments (n = 20) using 8-Br-cGMP, S-nitroso-N-acetylpenicillamine (SNAP), adenosine and pinacidil were carried out to elucidate whether this effect was related to changes in the general tone of the vessel. Additionally, the relationship between oscillations in vascular tone and intracellular calcium concentration was studied. Results: Induction of cGMP agonistic activity with either 8-Br-cGMP or zaprinast lowered the Vasomotion frequency significantly, whereas L-NAME-induced inhibition of cGMP increased this frequency. Neither of the agents affected the amplitude of the oscillations. The control experiments indicated that the effect of cGMP on Vasomotion frequency was independent of the accompanying increase in tone. The oscillations in tone during Vasomotion were accompanied by similar oscillations in intracellular calcium concentration. Conclusion: Cyclic GMP lowers the frequency without affecting the amplitude of Vasomotion in isolated porcine retinal arterioles.
Vladimir V. Matchkov - One of the best experts on this subject based on the ideXlab platform.
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Vasomotion what is currently thought
Acta Physiologica, 2011Co-Authors: Christian Aalkjaer, Donna Briggs Boedtkjer, Vladimir V. MatchkovAbstract:This minireview discusses Vasomotion, which is the oscillation in tone of blood vessels leading to flowmotion. We will briefly discuss the prevalence of Vasomotion and its potential physiological and pathophysiological relevance. We will also discuss the models that have been suggested to explain how a coordinated oscillatory activity of the smooth muscle tone can occur and emphasize the role of the endothelium, the handling of intracellular Ca(2+) and the role of smooth muscle cell ion conductances. It is concluded that Vasomotion is likely to enhance tissue dialysis, although this concept still requires more experimental verification, and that an understanding at the molecular level for the pathways leading to Vasomotion is beginning to emerge.
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Vasomotion – what is currently thought?
Acta physiologica (Oxford England), 2011Co-Authors: Christian Aalkjaer, Donna Briggs Boedtkjer, Vladimir V. MatchkovAbstract:This minireview discusses Vasomotion, which is the oscillation in tone of blood vessels leading to flowmotion. We will briefly discuss the prevalence of Vasomotion and its potential physiological and pathophysiological relevance. We will also discuss the models that have been suggested to explain how a coordinated oscillatory activity of the smooth muscle tone can occur and emphasize the role of the endothelium, the handling of intracellular Ca(2+) and the role of smooth muscle cell ion conductances. It is concluded that Vasomotion is likely to enhance tissue dialysis, although this concept still requires more experimental verification, and that an understanding at the molecular level for the pathways leading to Vasomotion is beginning to emerge.
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BESTROPHIN IS IMPORTANT FOR THE RHYTHMIC BUT NOT THE TONIC CONTRACTION IN RAT MESENTERIC SMALL ARTERIES
Cardiovascular Research, 2011Co-Authors: Torbjoern Broegger, Jens Christian Brings Jacobsen, Vibeke Secher Dam, Donna Briggs Boedtkjer, Henrik Kold-petersen, Finn Skou Pedersen, Christian Aalkjaer, Vladimir V. MatchkovAbstract:Aims We have previously characterized a cGMP-dependent Ca2+-activated Cl– current in vascular smooth muscle cells (SMCs) and have shown its dependence on bestrophin-3 expression. We hypothesize that this current is important for synchronization of SMCs in the vascular wall. In the present study, we aimed to test this hypothesis by transfecting rat mesenteric small arteries in vivo with siRNA specifically targeting bestrophin-3. Methods and results The arteries were tested 3 days after transfection in vitro for isometric force development and for intracellular Ca2+ in SMCs. Bestrophin-3 expression was significantly reduced compared with arteries transfected with mutated siRNA. mRNA levels for bestrophin-1 and -2 were also significantly reduced by bestrophin-3 down-regulation. This is suggested to be secondary to specific bestrophin-3 down-regulation since siRNAs targeting different exons of the bestrophin-3 gene had identical effects on bestrophin-1 and -2 expression. The transfection affected neither the maximal contractile response nor the sensitivity to norepinephrine and arginine-vasopressin. The amplitude of agonist-induced Vasomotion was significantly reduced in arteries down-regulated for bestrophins compared with controls, and asynchronous Ca2+ waves appeared in the SMCs. The average frequency of Vasomotion was not different. 8Br-cGMP restored Vasomotion in arteries where the endothelium was removed, but oscillation amplitude was still significantly less in bestrophin-down-regulated arteries. Thus, Vasomotion properties were consistent with those previously characterized for rat mesenteric small arteries. Data from our mathematical model are consistent with the experimental results. Conclusion This study demonstrates the importance of bestrophins for synchronization of SMCs and strongly supports our hypothesis for generation of Vasomotion.
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Vasomotion has chloride-dependency in rat mesenteric small arteries
Pflugers Archiv : European journal of physiology, 2008Co-Authors: Donna Briggs Boedtkjer, Vladimir V. Matchkov, Ebbe Boedtkjer, Holger Nilsson, Christian AalkjaerAbstract:The possibility that Ca2+-activated Cl− conductances (CaCCs) contribute to oscillations in vascular tone (Vasomotion) is tested in isolated mesenteric small arteries from rats where cGMP independent (ICl(Ca)) and cGMP-dependent (ICl(Ca,cGMP)) chloride conductances are important. The effect of anion substitution and Cl− channel blockers on noradrenaline (NA)-stimulated tension in isometrically mounted mesenteric arteries and for chloride conductance of smooth muscle cells isolated from these arteries were assessed electrophysiologically. Cl−o replacement with aspartate blocked Vasomotion while 36mM SCN−o (substituted for Cl−) was sufficient to inhibit Vasomotion. Oscillations in tone, membrane potential, and [Ca2+]i disappeared with 36mM SCN−. DIDS and Zn2+ blocked ICl(Ca,cGMP) but not ICl(Ca). Vasomotion was not sensitive to DIDS and Zn2+, and DIDS and Zn2+ induce Vasomotion in arteries without endothelium. The Vasomotion in the presence of DIDS and Zn2+ was sensitive to 36mM SCN−o. The anion substitution data indicate that Cl− is crucial for the Vm and [Ca2+]i oscillations underlying Vasomotion. The Cl− channel blocker data are consistent with both CaCCs being important.
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Hypothesis for the Initiation of Vasomotion
Circulation research, 2001Co-Authors: Hongli Peng, Christian Aalkjaer, Vladimir V. Matchkov, Anders Ivarsen, Holger NilssonAbstract:Abstract —Vasomotion is the regular variation in tone of arteries. In our study, we suggest a model for the initiation of Vasomotion. We suggest that intermittent release of Ca 2+ from the sarcoplasmic reticulum (SR, cytosolic oscillator), which is initially unsynchronized between the vascular smooth muscle cells, becomes synchronized to initiate Vasomotion. The synchronization is achieved by an ion current over the cell membrane, which is activated by the oscillating Ca 2+ release. This current results in an oscillating membrane potential, which synchronizes the SR in the vessel wall and starts Vasomotion. Therefore, the pacemaker of the vascular wall can be envisaged as a diffuse array of individual cytosolic oscillators that become entrained by a reciprocal interaction with the cell membrane. The model is supported by experimental data. Confocal [Ca 2+ ] i imaging and isometric force development in isolated rat resistance arteries showed that low norepinephrine concentrations induced SR-dependent unsynchronized waves of Ca 2+ in the vascular smooth muscle. In the presence of the endothelium, the waves converted to global synchronized oscillations of [Ca 2+ ] i after some time, and Vasomotion appeared. Synchronization was also seen in the absence of endothelium if 8-bromo-cGMP was added to the bath. Using the patch-clamp technique and microelectrodes, we showed that Ca 2+ release can activate an inward current in isolated smooth muscle cells from the arteries and cause depolarization. These electrophysiological effects of Ca 2+ release were cGMP dependent, which is consistent with the possibility that they are important for the cGMP-dependent synchronization. Further support for the model is the observation that a short-lasting current pulse can initiate Vasomotion in an unsynchronized artery as expected from the model.
Jean-jacques Meister - One of the best experts on this subject based on the ideXlab platform.
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Effects of Arterial Wall Stress on Vasomotion
Biophysical journal, 2006Co-Authors: Michèle Koenigsberger, Jean-louis Bény, Roger Sauser, Jean-jacques MeisterAbstract:Smooth muscle and endothelial cells in the arterial wall are exposed to mechanical stress. Indeed blood flow induces intraluminal pressure variations and shear stress. An increase in pressure may induce a vessel contraction, a phenomenon known as the myogenic response. Many muscular vessels present Vasomotion, i.e., rhythmic diameter oscillations caused by synchronous cytosolic calcium oscillations of the smooth muscle cells. Vasomotion has been shown to be modulated by pressure changes. To get a better understanding of the effect of stress and in particular pressure on Vasomotion, we propose a model of a blood vessel describing the calcium dynamics in a coupled population of smooth muscle cells and endothelial cells and the consequent vessel diameter variations. We show that a rise in pressure increases the calcium concentration. This may either induce or abolish Vasomotion, or increase its frequency depending on the initial conditions. In our model the myogenic response is less pronounced for large arteries than for small arteries and occurs at higher values of pressure if the wall thickness is increased. Our results are in agreement with experimental observations concerning a broad range of vessels.
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Role of the Endothelium on Arterial Vasomotion
Biophysical Journal, 2005Co-Authors: Michèle Koenigsberger, Jean-louis Bény, Roger Sauser, Jean-jacques MeisterAbstract:It is well-known that cyclic variations of the vascular diameter, a phenomenon called Vasomotion, are induced by synchronous calcium oscillations of smooth muscle cells (SMCs). However, the role of the endothelium on Vasomotion is unclear. Some experimental studies claim that the endothelium is necessary for synchronization and Vasomotion, whereas others report rhythmic contractions in the absence of an intact endothelium. Moreover, endothelium-derived factors have been shown to abolish Vasomotion by desynchronizing the calcium signals in SMCs. By modeling the calcium dynamics of a population of SMCs coupled to a population of endothelial cells, we analyze the effects of an SMC vasoconstrictor stimulation on endothelial cells and the feedback of endothelium-derived factors. Our results show that the endothelium essentially decreases the SMCs calcium level and may move the SMCs from a steady state to an oscillatory domain, and vice versa. In the oscillatory domain, a population of coupled SMCs exhibits synchronous calcium oscillations. Outside the oscillatory domain, the coupled SMCs present only irregular calcium flashings arising from noise modeling stochastic opening of channels. Our findings provide explanations for the published contradictory experimental observations.
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Calcium dynamics and Vasomotion in rat mesenteric arteries
Journal of cardiovascular pharmacology, 2004Co-Authors: Alexander Schuster, Nikolaos Stergiopulos, Hirotaka Oishi, Mathieu Lamboley, Jean-louis Bény, Céline Grange, Jean-jacques MeisterAbstract:Smooth muscle cell calcium dynamics and diameter were measured in intact pressurized rat mesenteric artery segments during vasoconstriction and Vasomotion. Arteries showed a certain norepinephrine (NE) threshold (0.3-0.4 microM) for the onset of Vasomotion, during a cumulative NE concentration-response curve. This was due to a necessary [Ca2+]i threshold (increase over basal level of 22.2 +/- 2.6%) to elicit oscillations. The calcium oscillations obtained were synchronous over the entire vessel length and phase-shifted (in advance by 1.7 +/- 0.3 seconds) with respect to the diameter oscillations. A similar result was obtained using a KCl depolarization to contract the arteries, even though the [Ca2+]i threshold was much smaller in this case (increase over basal level of 9.9 +/- 4.3%), as compared with the NE-elicited Vasomotion. Blockade of the Na+/K+-ATPase with 1 microM ouabain, or of the Na+/Ca2+ exchanger (NCX) with 1 microM KB-R 7943, did not abolish the calcium oscillations, thus showing that these two pumps are only modulatory elements, while on the other hand, voltage-gated calcium channels have been found to be important in the Vasomotion mechanism.
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Role of membrane potential in Vasomotion of isolated pressurized rat arteries.
Life sciences, 2002Co-Authors: Hirotaka Oishi, Jean-jacques Meister, Alexander Schuster, Mathieu Lamboley, Nikos Stergiopulos, Jean-louis BényAbstract:Vasomotion, the phenomenon of vessel diameter oscillation, regulates blood flow and resistance. The main parameters implicated in Vasomotion are particularly the membrane potential and the cytosolic free calcium in smooth muscle cells. In this study, these parameters were measured in rat perfused-pressurized mesenteric artery segments. The application of norepinephrine (NE) caused rhythmic diameter contractions and membrane potential oscillations (amplitude; 5.3 +/- 0.3 mV, frequency; 0.09 +/- 0.01 Hz). Verapamil (1 microM) abolished this Vasomotion. During Vasomotion, 10(-5) M ouabain (Na(+)-K(+) ATPase inhibitor) decreased the amplitude of the electrical oscillations but not their frequency (amplitude; 3.7 +/- 0.3 mV, frequency; 0.08 +/- 0.002 Hz). Although a high concentration of ouabain (10(-3) M) (which exhibits non-specific effects) abolished both electrical membrane potential oscillations and Vasomotion, we conclude that the Na+-K+ ATPase could not be implicated in the generation of the membrane potential oscillations. We conclude that in rat perfused-pressurized mesenteric artery, the slow wave membrane type of potential oscillation by rhythmically gating voltage-dependent calcium channels, is responsible for the oscillation of intracellular calcium and thus Vasomotion.
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Arterial Vasomotion: effect of flow and evidence of nonlinear dynamics
The American journal of physiology, 1998Co-Authors: Nikolaos Stergiopulos, C.-a. Porret, S. De Brouwer, Jean-jacques MeisterAbstract:Vasomotion has been studied on segments of rat mesenteric and femoral arteries perfused in vitro. We have investigated 1) the effect of perfusion flow on the characteristics of Vasomotion and 2) the nature and patterns of Vasomotion. We have found that perfusion flow is not a control parameter that contributes to the genesis of Vasomotion but that it affects, in most cases only slightly, the frequency and amplitude of Vasomotion. We have found evidence that Vasomotion is low-dimensional chaotic. The correlation dimension ranged between 2 and 4, and the average Lyapunov's coefficient was approximately 0.1. A great variety of Vasomotion patterns was observed with features that are typical of nonlinear deterministic systems: regular and irregular Vasomotion, quasiperiodicity, period doubling and higher-order periods, intermittency, mixed modes, and bursting activity. Vasomotion patterns appeared occasionally to be highly sensitive to perturbations in perfusion flow, which also supported the existence of nonlinear dynamics. Finally, entrainment (phase locking) was observed when arteries were perfused with oscillatory flow with frequency in the neighborhood of the frequency of Vasomotion.
Donna Briggs Boedtkjer - One of the best experts on this subject based on the ideXlab platform.
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Vasomotion what is currently thought
Acta Physiologica, 2011Co-Authors: Christian Aalkjaer, Donna Briggs Boedtkjer, Vladimir V. MatchkovAbstract:This minireview discusses Vasomotion, which is the oscillation in tone of blood vessels leading to flowmotion. We will briefly discuss the prevalence of Vasomotion and its potential physiological and pathophysiological relevance. We will also discuss the models that have been suggested to explain how a coordinated oscillatory activity of the smooth muscle tone can occur and emphasize the role of the endothelium, the handling of intracellular Ca(2+) and the role of smooth muscle cell ion conductances. It is concluded that Vasomotion is likely to enhance tissue dialysis, although this concept still requires more experimental verification, and that an understanding at the molecular level for the pathways leading to Vasomotion is beginning to emerge.
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Vasomotion – what is currently thought?
Acta physiologica (Oxford England), 2011Co-Authors: Christian Aalkjaer, Donna Briggs Boedtkjer, Vladimir V. MatchkovAbstract:This minireview discusses Vasomotion, which is the oscillation in tone of blood vessels leading to flowmotion. We will briefly discuss the prevalence of Vasomotion and its potential physiological and pathophysiological relevance. We will also discuss the models that have been suggested to explain how a coordinated oscillatory activity of the smooth muscle tone can occur and emphasize the role of the endothelium, the handling of intracellular Ca(2+) and the role of smooth muscle cell ion conductances. It is concluded that Vasomotion is likely to enhance tissue dialysis, although this concept still requires more experimental verification, and that an understanding at the molecular level for the pathways leading to Vasomotion is beginning to emerge.
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BESTROPHIN IS IMPORTANT FOR THE RHYTHMIC BUT NOT THE TONIC CONTRACTION IN RAT MESENTERIC SMALL ARTERIES
Cardiovascular Research, 2011Co-Authors: Torbjoern Broegger, Jens Christian Brings Jacobsen, Vibeke Secher Dam, Donna Briggs Boedtkjer, Henrik Kold-petersen, Finn Skou Pedersen, Christian Aalkjaer, Vladimir V. MatchkovAbstract:Aims We have previously characterized a cGMP-dependent Ca2+-activated Cl– current in vascular smooth muscle cells (SMCs) and have shown its dependence on bestrophin-3 expression. We hypothesize that this current is important for synchronization of SMCs in the vascular wall. In the present study, we aimed to test this hypothesis by transfecting rat mesenteric small arteries in vivo with siRNA specifically targeting bestrophin-3. Methods and results The arteries were tested 3 days after transfection in vitro for isometric force development and for intracellular Ca2+ in SMCs. Bestrophin-3 expression was significantly reduced compared with arteries transfected with mutated siRNA. mRNA levels for bestrophin-1 and -2 were also significantly reduced by bestrophin-3 down-regulation. This is suggested to be secondary to specific bestrophin-3 down-regulation since siRNAs targeting different exons of the bestrophin-3 gene had identical effects on bestrophin-1 and -2 expression. The transfection affected neither the maximal contractile response nor the sensitivity to norepinephrine and arginine-vasopressin. The amplitude of agonist-induced Vasomotion was significantly reduced in arteries down-regulated for bestrophins compared with controls, and asynchronous Ca2+ waves appeared in the SMCs. The average frequency of Vasomotion was not different. 8Br-cGMP restored Vasomotion in arteries where the endothelium was removed, but oscillation amplitude was still significantly less in bestrophin-down-regulated arteries. Thus, Vasomotion properties were consistent with those previously characterized for rat mesenteric small arteries. Data from our mathematical model are consistent with the experimental results. Conclusion This study demonstrates the importance of bestrophins for synchronization of SMCs and strongly supports our hypothesis for generation of Vasomotion.
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Vasomotion has chloride-dependency in rat mesenteric small arteries
Pflugers Archiv : European journal of physiology, 2008Co-Authors: Donna Briggs Boedtkjer, Vladimir V. Matchkov, Ebbe Boedtkjer, Holger Nilsson, Christian AalkjaerAbstract:The possibility that Ca2+-activated Cl− conductances (CaCCs) contribute to oscillations in vascular tone (Vasomotion) is tested in isolated mesenteric small arteries from rats where cGMP independent (ICl(Ca)) and cGMP-dependent (ICl(Ca,cGMP)) chloride conductances are important. The effect of anion substitution and Cl− channel blockers on noradrenaline (NA)-stimulated tension in isometrically mounted mesenteric arteries and for chloride conductance of smooth muscle cells isolated from these arteries were assessed electrophysiologically. Cl−o replacement with aspartate blocked Vasomotion while 36mM SCN−o (substituted for Cl−) was sufficient to inhibit Vasomotion. Oscillations in tone, membrane potential, and [Ca2+]i disappeared with 36mM SCN−. DIDS and Zn2+ blocked ICl(Ca,cGMP) but not ICl(Ca). Vasomotion was not sensitive to DIDS and Zn2+, and DIDS and Zn2+ induce Vasomotion in arteries without endothelium. The Vasomotion in the presence of DIDS and Zn2+ was sensitive to 36mM SCN−o. The anion substitution data indicate that Cl− is crucial for the Vm and [Ca2+]i oscillations underlying Vasomotion. The Cl− channel blocker data are consistent with both CaCCs being important.
Holger Nilsson - One of the best experts on this subject based on the ideXlab platform.
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Vasomotion has chloride-dependency in rat mesenteric small arteries
Pflugers Archiv : European journal of physiology, 2008Co-Authors: Donna Briggs Boedtkjer, Vladimir V. Matchkov, Ebbe Boedtkjer, Holger Nilsson, Christian AalkjaerAbstract:The possibility that Ca2+-activated Cl− conductances (CaCCs) contribute to oscillations in vascular tone (Vasomotion) is tested in isolated mesenteric small arteries from rats where cGMP independent (ICl(Ca)) and cGMP-dependent (ICl(Ca,cGMP)) chloride conductances are important. The effect of anion substitution and Cl− channel blockers on noradrenaline (NA)-stimulated tension in isometrically mounted mesenteric arteries and for chloride conductance of smooth muscle cells isolated from these arteries were assessed electrophysiologically. Cl−o replacement with aspartate blocked Vasomotion while 36mM SCN−o (substituted for Cl−) was sufficient to inhibit Vasomotion. Oscillations in tone, membrane potential, and [Ca2+]i disappeared with 36mM SCN−. DIDS and Zn2+ blocked ICl(Ca,cGMP) but not ICl(Ca). Vasomotion was not sensitive to DIDS and Zn2+, and DIDS and Zn2+ induce Vasomotion in arteries without endothelium. The Vasomotion in the presence of DIDS and Zn2+ was sensitive to 36mM SCN−o. The anion substitution data indicate that Cl− is crucial for the Vm and [Ca2+]i oscillations underlying Vasomotion. The Cl− channel blocker data are consistent with both CaCCs being important.
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Vasomotion: cellular background for the oscillator and for the synchronization of smooth muscle cells
British journal of pharmacology, 2005Co-Authors: Christian Aalkjaer, Holger NilssonAbstract:1 Vasomotion is the oscillation of vascular tone with frequencies in the range from 1 to 20 min−1 seen in most vascular beds. The oscillation originates in the vessel wall and is seen both in vivo and in vitro. 2 Recently, our ideas on the cellular mechanisms responsible for Vasomotion have improved. Three different types of cellular oscillations have been suggested. One model has suggested that oscillatory release of Ca2+ from intracellular stores is important (the oscillation is based on a cytosolic oscillator). A second proposed mechanism is an oscillation originating in the sarcolemma (a membrane oscillator). A third mechanism is based on an oscillation of glycolysis (metabolic oscillator). For the two latter mechanisms, only limited experimental evidence is available. 3 To understand Vasomotion, it is important to understand how the cells synchronize. For the cytosolic oscillators synchronization may occur via activation of Ca2+-sensitive ion channels by oscillatory Ca2+ release. The ensuing membrane potential oscillation feeds back on the intracellular Ca2+ stores and causes synchronization of the Ca2+ release. While membrane oscillators in adjacent smooth muscle cells could be synchronized through the same mechanism that sets up the oscillation in the individual cells, a mechanism to synchronize the metabolic-based oscillators has not been suggested. 4 The interpretation of the experimental observations is supported by theoretical modelling of smooth muscle cells behaviour, and the new insight into the mechanisms of Vasomotion has the potential to provide tools to investigate the physiological role of Vasomotion. British Journal of Pharmacology (2005) 144, 605–616. doi:10.1038/sj.bjp.0706084
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Vasomotion: mechanisms and physiological importance.
Molecular interventions, 2003Co-Authors: Holger Nilsson, Christian AalkjaerAbstract:That smooth muscles dilate and contract rhythmically has been known for a long time and the phenomenon has been studied for nearly as long. However, the causes and effects of smooth muscle oscillation (termed Vasomotion) are far from clear. It is thought that Vasomotion aids the delivery of oxygen to tissues surrounding capillary beds. On the other hand, unregulated Vasomotion might participate in the development and maintenance of pathophysiological states. Nilsson and Aalkjaer review what is known about Vasomotion and its consequences.
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Hypothesis for the Initiation of Vasomotion
Circulation research, 2001Co-Authors: Hongli Peng, Christian Aalkjaer, Vladimir V. Matchkov, Anders Ivarsen, Holger NilssonAbstract:Abstract —Vasomotion is the regular variation in tone of arteries. In our study, we suggest a model for the initiation of Vasomotion. We suggest that intermittent release of Ca 2+ from the sarcoplasmic reticulum (SR, cytosolic oscillator), which is initially unsynchronized between the vascular smooth muscle cells, becomes synchronized to initiate Vasomotion. The synchronization is achieved by an ion current over the cell membrane, which is activated by the oscillating Ca 2+ release. This current results in an oscillating membrane potential, which synchronizes the SR in the vessel wall and starts Vasomotion. Therefore, the pacemaker of the vascular wall can be envisaged as a diffuse array of individual cytosolic oscillators that become entrained by a reciprocal interaction with the cell membrane. The model is supported by experimental data. Confocal [Ca 2+ ] i imaging and isometric force development in isolated rat resistance arteries showed that low norepinephrine concentrations induced SR-dependent unsynchronized waves of Ca 2+ in the vascular smooth muscle. In the presence of the endothelium, the waves converted to global synchronized oscillations of [Ca 2+ ] i after some time, and Vasomotion appeared. Synchronization was also seen in the absence of endothelium if 8-bromo-cGMP was added to the bath. Using the patch-clamp technique and microelectrodes, we showed that Ca 2+ release can activate an inward current in isolated smooth muscle cells from the arteries and cause depolarization. These electrophysiological effects of Ca 2+ release were cGMP dependent, which is consistent with the possibility that they are important for the cGMP-dependent synchronization. Further support for the model is the observation that a short-lasting current pulse can initiate Vasomotion in an unsynchronized artery as expected from the model.
