2.Multiple regulatory effects of angiotensin II on the large-conductance Ca- and voltage-activated potassium channel in vascular smooth muscle cells.
Xiao-Chen YIN ; Su-Li ZHANG ; Hui-Rong LIU
Acta Physiologica Sinica 2019;71(2):187-195
Renin-angiotensin system (RAS) is involved in the regulation of vascular smooth muscle cell (VSMC) tension. Angiotensin II (Ang II) as the main effector molecule of RAS can increase the intracellular Ca concentration and cause VSMCs contraction by activating angiotensin II type 1 receptor (AT1R). The large-conductance Ca- and voltage-activated potassium (BK) channel is an essential potassium channel in VSMCs, playing an important role in maintaining membrane potential and intracellular potassium-calcium balance. The BK channel in VSMCs mainly consists of α and β1 subunits. Functional BKα subunits contain voltage-sensors and Ca binding sites. Hence, increase in the membrane potential or intracellular Ca concentration can trigger the opening of the BK channel by mediating transient K outward current in a negative regulatory manner. However, increasing evidence has shown that although Ang II can raise the intracellular Ca concentration, it also inhibits the expression and function of the BK channel by activating the PKC pathway, internalizing AT1R-BKα heterodimer, or dissociating α and β1 subunits. Under some specific conditions, Ang II can also activate the BK channel, but the underlying mechanism remains unknown. In this review, we summarize the potential mechanisms underlying the inhibitory or activating effect of Ang II on the BK channel, hoping that it could provide a theoretical basis for improving intracellular ion imbalance.
Angiotensin II
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physiology
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Calcium
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physiology
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Humans
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Large-Conductance Calcium-Activated Potassium Channels
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physiology
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Muscle, Smooth, Vascular
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cytology
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Myocytes, Smooth Muscle
;
physiology
;
Renin-Angiotensin System
3.Recent progress in smooth muscle autophagy of vascular diseases.
Shi TAI ; Qin ZHOU ; Yanan GUO ; Shenghua ZHOU
Journal of Central South University(Medical Sciences) 2018;43(8):920-928
Autophagy plays a crucial role in maintaining normal structure and vascular function in vivo. When stress-relevant stimuli are involved, the increases of autophagy can protect vascular smooth muscle cells, promote cell survival, and phenotype transformation, as well as reduce calcification. On the contrary, the decrease of autophagy can accelerate cell senescence, resulting in structural changes and dysfunction of vasomotor and vasodilation. However, excessive activation of autophagy can induce the damage of the healthy protein and essential organelles, and even lead to autophagic cell death, accelerating the progression of vascular disease. Thus, the precise targeting of autophagy opens a novel way for treatment of vascular diseases.
Autophagy
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physiology
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Cell Survival
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Cellular Senescence
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Disease Progression
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Humans
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Muscle, Smooth, Vascular
;
cytology
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Myocytes, Smooth Muscle
;
physiology
;
Vascular Diseases
;
pathology
;
therapy
4.ATP and adenosine in the regulation of skeletal muscle blood flow during exercise.
Acta Physiologica Sinica 2014;66(1):67-78
Adenosine was identified as a regulator of skeletal muscle blood flow almost 50 years ago. It was first proposed that increased use of ATP during muscle contractions led to net ATP breakdown, and its breakdown product, adenosine, diffused through the interstitial space to the blood stream to be washed away. En-route to its removal, adenosine was suggested to relax the vascular smooth muscle, thereby increasing the blood flow and oxygen supply to the contracting muscle. This mechanism has been researched quite intensively over the years, yet there are still many aspects that remain unclear. It has been confirmed that adenosine does, indeed, relax vascular smooth muscle and contribute to exercise hyperaemia, but the discovery that adenosine was formed extracellularly has shifted the research focus onto its precursor, ATP. ATP is released from many tissues, and produces many effects, including both vasodilation and vasoconstriction, as well as modulation of the neural mechanisms for skeletal muscle blood flow control. This review summarizes the current state of knowledge on the contributions of adenosine and ATP to the skeletal muscle vasodilation that accompanies contractile activity.
Adenosine
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physiology
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Adenosine Triphosphate
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physiology
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Exercise
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physiology
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Hemodynamics
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Humans
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Muscle Contraction
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Muscle, Skeletal
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blood supply
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Muscle, Smooth, Vascular
;
physiology
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Regional Blood Flow
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physiology
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Vasoconstriction
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Vasodilation
5.Effect of removal of the adventitia on vascular remodeling and vasoconstriction in rabbits.
Hua-Ming MU ; Zhi-Ming ZHU ; Hai-Yan WANG ; Li-Juan WANG
Acta Physiologica Sinica 2003;55(3):290-295
The aim of the present study was to investigate the effect of removal of the adventitia on vascular remodeling and vasoconstriction of the carotid artery in New Zealand rabbit. Adventitia of carotid artery was removed mechanically. The histology, morphology and reactivity of the carotid artery was observed by immunohistochemistry and measurement of carotid ring tension immediately, 1 week and 2 weeks after removal of the adventitia. No damage of intima and media was observed after removing the adventitia. Removal of the adventitia caused a remarkable proliferation of the vascular media and formed the neointima. Compared with the control ring, norepinephrine (NE)-induced vasocontraction in adventitia-denuded carotid artery was significantly reduced immediately and 1 week after the operation (P<0.05). Adventitia removal promoted the neointima formation and decreased vasoconstriction of the carotid artery, indicating that the adventitia is involved in the regulation of vascular remodeling and vasoconstriction.
Animals
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Carotid Arteries
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pathology
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physiology
;
surgery
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Connective Tissue
;
physiology
;
surgery
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Muscle, Smooth, Vascular
;
pathology
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Rabbits
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Tunica Intima
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pathology
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Vasoconstriction
;
physiology
6.Comparison of biomechanical behavior of cerebral and mesenteric small arteries of simulated microgravity rats.
Jiu-Hua CHENG ; Macro BOSCOLO ; Le-Jian LIN ; Yun-Gang BAI ; Xiang ZHANG ; Jin MA ; Li-Fan ZHANG
Acta Physiologica Sinica 2009;61(4):386-394
The aim of the present study was to further elucidate the mechanisms of vascular adaptation to microgravity and its gravity-based countermeasure by a biomechanical approach. Active (the dissected vessel segment was superfused with PPS) and passive (while it was superfused with Ca(2+)-free PPS) biomechanical properties of mesenteric third-order small arteries and middle cerebral arteries isolated from 3-day simulated microgravity (SUS), countermeasure (STD, daily 1 h of -G(x) gravitation), and control (CON) groups of rats were studied. The following mechanical parameters were calculated: the overall stiffness parameter of passive vessels (beta), circumferential stress (sigma(theta))-strain (epsilon(theta)) relationship, and pressure-dependent incremental elastic modulus (E(inc,p)) of both active and passive vessels, and vascular smooth muscle (VSM) activity-dependent incremental modulus (E(inc,a)). Results from the analysis of active biomechanical properties revealed the contribution of vascular smooth muscle (VSM) tone during the early adaptation to microgravity: (1) For mesenteric small arteries, active circumferential sigma(theta) -epsilon(theta) curve of SUS group was comparable with that of the passive vessels, indicating that the function of VSM to restore the normal stress distribution is compromised; however, this mal-adaptation was fully prevented by the countermeasure of daily 1 h of -G(x) gravitation; (2) For the middle cerebral arteries, active circumferential sigma(theta) -epsilon(theta) relation of SUS group was shifted to the left side of the passive curve and epsilon(theta) was kept at a nearly constant level with the corresponding sigma(theta) being at its normal range; furthermore, the enhanced myogenic tone responsiveness was not prevented by daily short-duration -G(x). Analysis of the passive biomechanical properties has suggested remodeling changes in matrix components of different types of vessels, which might be significant if the exposure duration was further prolonged. In brief, studies of vascular biomechanics are of particular importance in elucidating the mechanisms underlying vascular adaptation to microgravity and its gravity-based countermeasure.
Animals
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Biomechanical Phenomena
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Mesenteric Arteries
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physiology
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Middle Cerebral Artery
;
physiology
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Muscle, Smooth, Vascular
;
physiology
;
Pressure
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Rats
;
Weightlessness Simulation
7.The effects of pH0 on electrophysiological properties of VSMCs in brain artery of spontaneously hypertensive rats.
Yuan-yuan SHANG ; Jun-qiang SI ; Li LI ; Yu LIAN ; Ke-tao MA
Chinese Journal of Applied Physiology 2012;28(3):268-270
OBJECTIVETo investigate the effects of pH0 on the electrophysiological properties of vascular smooth muscle cells (VSMCs) in brain artery of spontaneously hypertension rats (SHR).
METHODSWe studied the effects and the ion mechanism of pH0 on whole-cell membrane current of VSMCs in brain artery of 200 - 250 g SHR by whole-cell patch clamp recordings.
RESULTS1. Acidic pH0 could inhibit the outward current of VSMCs of brain artery in SHR in a voltage-dependent manner. It induced a more pronounced inhibition of the outward current from 0 to + 60mV; 2. In the presence of 1 mmol/L TEA, the inhibition of acidic pH0 on the outward current of VSMCs of brain artery was inhibited.
CONCLUSIONThe changes of outward current of VSMCs of brain artery in SHR induced by pH0 may be connected with BKCa channel.
Animals ; Cerebral Arteries ; cytology ; Electrophysiological Phenomena ; Extracellular Fluid ; physiology ; Hydrogen-Ion Concentration ; Muscle, Smooth, Vascular ; physiology ; Rats ; Rats, Inbred SHR
8.Characteristic of spontaneous transient outward potassium currents in vascular smooth muscle cells of porcine coronary artery.
Fang CAI ; Peng-Yun LI ; Yan YANG ; Zhi-Fei LIU ; Miao-Ling LI ; Wen ZHOU ; Jie PEI ; Jun CHENG ; Huan LAN ; Joachim B GRAMMER ; Xiao-Rong ZENG
Acta Physiologica Sinica 2007;59(1):27-34
Spontaneous transient outward currents (STOCs) play an important role in the myogenic regulation of small artery tone, such as coronary artery. In the present study, we investigated the electrophysiological properties and the regulation of STOCs in vascular smooth muscle cells (VSMCs) of porcine coronary artery by perforated patch-clamp technique. Our data showed that STOCs were dependent on voltage and extracellular calcium and they were highly variable in amplitudes and frequencies. STOCs superimposed stochastically onto whole-cell K(+) currents induced by step and ramp protocols. STOCs were completely abolished by ChTX [inhibitor of large-conductance Ca(2+)-activated potassium (BK(Ca)) channels], removal of extracellular Ca(2+), or addition of ryanodine (50 mumol/L) respectively. In contrast, CdCl2 and verapamil, inhibitors of voltage-dependent L-type Ca(2+) channels, had little effect on STOCs. Caffeine (5 mmol/L) transiently increased STOCs (hump), followed by a temporary inhibition. Ca(2+) ionophore A23187 increased both amplitude and frequency of STOCs. Na(+) ionophore monensin increased the frequency of STOCs. STOCs were strongly inhibited by KB-R7943, a selective inhibitor of the reverse mode of the Na(+)/Ca(2+) exchanger. Based on these observations, we conclude that STOCs are mediated by BK(Ca) channels. The generation and activation of STOCs depend upon Ca(2+) influx through Na(+)/Ca(2+) exchange and release of Ca(2+) from sarcoplasmic reticulum (SR) via ryanodine receptors. This suggests that Na(+)/Ca(2+) exchange determines calcium store refilling. Recycling of entering Ca(2+) from superficial SR may locally elevate Ca(2+) concentration at the plasma membrane, thereby activating BK(Ca) channels and then initiating STOCs.
Animals
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Coronary Vessels
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cytology
;
physiology
;
Electrophysiological Phenomena
;
physiology
;
Muscle, Smooth, Vascular
;
cytology
;
physiology
;
Myocytes, Smooth Muscle
;
cytology
;
physiology
;
Patch-Clamp Techniques
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Potassium Channels, Calcium-Activated
;
physiology
;
Sodium-Calcium Exchanger
;
physiology
;
Swine
9.Comparison of membrane current of vascular smooth muscle cells in brain artery of spontaneously hypertensive rats and Wistar rats.
Lei ZHAO ; Yuan-Yuan SHANG ; Jun-Qiang SI ; Xin-Zhi LI ; Li LI ; Zhong-Shuang ZHANG ; Ke-Tao MA
Chinese Journal of Applied Physiology 2013;29(1):25-28
OBJECTIVETo investigate the difference in membrane current of vascular smooth muscle cells (VSMCs) in brain artery (BA) of spontaneously hypertensive rats (SHR) and Wistar rats.
METHODSWe compared the properties of spontaneous transient outward K+ currents (STOCs), the density and composition of current of VSMCs in BA of SHR and Wistar rats by whole-cell patch clamp technique.
RESULTS(1) When the command voltage was 0, + 20, + 40 and + 60 mV respectively, the current densities of VSMCs in BA of SHR and Wistar rats were significant different (P < 0.01). (2) The whole-cell current of VSMCs was partly inhibited by 1 mmol/L4-AP (voltage-gated K+ channel blocker) or 1 mmol/L TEA (big conductance Ca(2+)-activated K+ channel blocker) respectively. (3) The frequency and amplitude of STOCs in SHR were faster and bigger than those in Wistar rats. 1 mmol/L TEA almostly inhibited the STOCs, but not by 4-AP.
CONCLUSIONThese results suggest that the current densities of VSMCs in BA of SHR and Wistar rats are significant different, the outward current of VSMCs in BA of SHR and Wistar rats are composed by Kv and BK(Ca). SHR express more STOCs mediated by BK(Ca), than Wistar rats.
Animals ; Cerebral Arteries ; cytology ; physiology ; Membrane Potentials ; physiology ; Muscle, Smooth, Vascular ; cytology ; physiology ; Myocytes, Smooth Muscle ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated ; physiology ; Potassium Channels, Voltage-Gated ; physiology ; Rats ; Rats, Inbred SHR ; Rats, Wistar
10.Tissue engineering a blood vessel substitute: the role of biomechanics.
Yonsei Medical Journal 2000;41(6):735-739
The engineering of a functional blood vessel substitute has for a quarter of a century been a "holy grail" within the cardiovascular research community. Such a substitute must exhibit long term patency, and the critical issues in this area in many ways are influenced by biomechanics. One of the requirements is that it must be non-thrombogenic, which requires an "endothelial-like" inner lining. It also must have mechanical strength, i.e. a burst pressure, sufficient to operate at arterial pressures. Ideally, however, it must be more than this. It also must have viscoelastic properties that match those of the native vessel being replaced. Finally, if it is to be able to adapt to changing blood flow conditions, it must exhibit vasoactivity, a function which in and of itself can be viewed as biomechanical in nature. To achieve this requires having, as part of the construct, vascular smooth muscle cells, which are contractile in nature and oriented in a circumferential direction. Only if an engineered blood vessel substitute possesses all of these functional characteristics, can one say that the functionality exhibited by a native vessel is being mimicked.
Artificial Organs*
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Biomechanics
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Biomedical Engineering*
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Blood Vessels*
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Endothelium, Vascular/physiology
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Human
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Muscle, Smooth, Vascular/physiology
;
Support, U.S. Gov't, Non-P.H.S.
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Thrombosis/etiology
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Vasomotor System/physiology