Mechanisms of Direct Inhibitory Action of Isoflurane on Vascular Smooth Muscle of Mesenteric Resistance Arteries

2003 ◽  
Vol 99 (3) ◽  
pp. 666-677 ◽  
Author(s):  
Takashi Akata ◽  
Tomoo Kanna ◽  
Jun Yoshino ◽  
Shosuke Takahashi
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Reactivity ◽  
Channel Blocker ◽  
Isometric Force ◽  
Systemic Resistance ◽  
Resistance Arteries ◽  
Voltage Gated ◽  
Fura 2 ◽  
Force Relation

Background Isoflurane has been shown to directly inhibit vascular reactivity. However, less information is available regarding its underlying mechanisms in systemic resistance arteries. Methods Endothelium-denuded smooth muscle strips were prepared from rat mesenteric resistance arteries. Isometric force and intracellular Ca2+ concentration ([Ca2+]i) were measured simultaneously in the fura-2-loaded strips, whereas only the force was measured in the beta-escin membrane-permeabilized strips. Results Isoflurane (3-5%) inhibited the increases in both [Ca2+]i and force induced by either norepinephrine (0.5 microM) or KCl (40 mM). These inhibitions were similarly observed after depletion of intracellular Ca2+ stores by ryanodine. Regardless of the presence of ryanodine, after washout of isoflurane, its inhibition of the norepinephrine response (both [Ca2+]i and force) was significantly prolonged, whereas that of the KCl response was quickly restored. In the ryanodine-treated strips, the norepinephrine- and KCl-induced increases in [Ca2+]i were both eliminated by nifedipine, a voltage-gated Ca2+ channel blocker, whereas only the former was inhibited by niflumic acid, a Ca2+-activated Cl- channel blocker. Isoflurane caused a rightward shift of the Ca2+-force relation only in the fura-2-loaded strips but not in the beta-escin-permeabilized strips. Conclusions In mesenteric resistance arteries, isoflurane depresses vascular smooth muscle reactivity by directly inhibiting both Ca2+ mobilization and myofilament Ca2+ sensitivity. Isoflurane inhibits both norepinephrine- and KCl-induced voltage-gated Ca2+ influx. During stimulation with norepinephrine, isoflurane may prevent activation of Ca2+-activated Cl- channels and thereby inhibit voltage-gated Ca2+ influx in a prolonged manner. The presence of the plasma membrane appears essential for its inhibition of the myofilament Ca2+ sensitivity.

Mechanisms of Direct Inhibitory Action of Ketamine on Vascular Smooth Muscle in Mesenteric Resistance Arteries

2001 ◽  
Vol 95 (2) ◽  
pp. 452-462 ◽  
Author(s):  
Takashi Akata ◽  
Kaoru Izumi ◽  
Mikio Nakashima
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Direct Evidence ◽  
Contractile Response ◽  
Isometric Force ◽  
Mesenteric Arteries ◽  
Systemic Resistance ◽  
Resistance Arteries ◽  
Fura 2 ◽  
Force Relation

Background Ketamine was previously suggested to relax vascular smooth muscle by reducing the intracellular Ca2+ concentration ([Ca2+]i). However, no direct evidence is available to indicate that ketamine reduces the [Ca2+]i in vascular smooth muscle of systemic resistance arteries. Methods Endothelium-intact or -denuded smooth muscle strips were prepared from rat small mesenteric arteries. Isometric force and [Ca2+]i were measured simultaneously in the fura-2-loaded, endothelium-denuded strips. In some experiments, only isometric force was measured in either the endothelium-intact or beta-escin-treated, endothelium-denuded strips. Results In the endothelium-intact strips, lower concentrations (< or = 30 microm) of ketamine slightly enhanced norepinephrine-induced contraction, whereas higher concentrations (> or = 100 microM) of ketamine inhibited both norepinephrine- and KCl-induced contractions. In the fura-2-loaded strips, ketamine (> or = 100 microM) inhibited the increases in both [Ca2+]i and force induced by either norepinephrine or KCl. Ketamine also inhibited the norepinephrine-induced increase in [Ca2+]i after treatment with ryanodine. In the absence of extracellular Ca2+, ketamine notably inhibited the norepinephrine-induced increase in [Ca2+]i, whereas it only minimally inhibited caffeine-induced increase in [Ca2+]i. Ketamine had little influence on the [Ca2+]i-force relation during force development to stepwise increment of extracellular Ca2+ concentration during either KCl depolarization or norepinephrine stimulation. Ketamine did not affect Ca2+-activated contractions in the beta-escin membrane-permeabilized strips. Conclusions The action of ketamine on contractile response to norepinephrine consists of endothelium-dependent vasoconstricting and endothelium-independent vasodilating components. The direct vasorelaxation is largely a result of reduction of[Ca2+]i in vascular smooth muscle cells. The [Ca2+]i-reducing effects are caused by inhibitions of both voltage-gated Ca2+ influx and norepinephrine-induced Ca2+ release from the intracellular stores.

The Action of Sevoflurane on Vascular Smooth Muscle of Isolated Mesenteric Resistance Arteries (Part 2)

2000 ◽  
Vol 92 (5) ◽  
pp. 1441-1453 ◽  
Author(s):  
Takashi Akata ◽  
Kaoru Izumi ◽  
Mikio Nakashima
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Permeabilized Cells ◽  
Fura 2 ◽  
Force Relation ◽  
Intact Muscle

Background The precise mechanisms behind the direct inhibitory action of sevoflurane on vascular smooth muscle have not been fully elucidated. Methods Endothelium-denuded smooth muscle strips were prepared from rat small mesenteric arteries. Isometric force and intracellular Ca2+ concentration ([Ca2+]i) were measured simultaneously in the fura-2-loaded strips. In another series of experiments, only isometric force was measured in the beta-escin-membrane-permeabilized strips. Results Sevoflurane (3-5%) inhibited the increases in both the [Ca2+]i and the force induced by either norepinephrine (0.5-10 microm) or 40 mm K+. Sevoflurane still inhibited the increase in [Ca2+]i induced by norepinephrine after depletion of intracellular Ca2+ stores with ionomycin, although it little influenced the increase in [Ca2+]i induced by norepinephrine after treatment with verapamil. In the fura-2-loaded membrane-intact muscle, sevoflurane caused a rightward shift of Ca2+-force relation during force development to stepwise increment of extracellular Ca2+ concentration during 40-mm K+ depolarization in either the presence or the absence of norepinephrine. In contrast, sevoflurane did not influence Ca2+-activated contraction in the beta-escin-permeabilized muscle, in which alpha-adrenergic receptor coupling was not retained. Conclusions The inhibitory effects of sevoflurane on both norepinephrine- and potassium chloride (KCl)-induced contractions are caused by reduction of [Ca2+]i in vascular smooth muscle and inhibition of the myofilament Ca2+ sensitivity. The [Ca2+]i-reducing effect of sevoflurane observed in both the norepinephrine- and the K+-stimulated muscle is mainly caused by inhibition of voltage-gated Ca2+ influx. The inhibitory effect of sevoflurane on Ca2+ activation of contractile proteins seems to be mediated by the cell membrane or by some diffusible substances that are lost in the beta-escin-permeabilized cells.

Comparison of Volatile Anesthetic Actions on Intracellular Calcium Stores of Vascular Smooth Muscle

2001 ◽  
Vol 94 (5) ◽  
pp. 840-850 ◽  
Author(s):  
Takashi Akata ◽  
Mikio Nakashima ◽  
Kaoru Izumi
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Isometric Force ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Mesenteric Arteries ◽  
Systemic Resistance ◽  
Release Mechanism ◽  
Calcium Stores ◽  
Resistance Arteries

Background Volatile anesthetic actions on intracellular Ca2+ stores (ie., sarcoplasmic reticulum [SR]) of vascular smooth muscle have not been fully elucidated. Methods Using isometric force recording method and fura-2 fluorometry, the actions of four volatile anesthetics on SR were studied in isolated endothellum-denuded rat mesenteric arteries. Results Halothane (> or = 3%) and enflurane (> or = 3%), but not isoflurane and sevoflurane, increased the intracellular Ca2+ concentration ([Ca2+]i) in Ca2+-free solution. These Ca2+-releasing actions were eliminated by procaine. When each anesthetic was applied during Ca2+ loading, halothane (> or = 3%) and enflurane (5%), but not isoflurane and sevoflurane, decreased the amount of Ca2+ in the SR. However, if halothane or enflurane was applied with procaine during Ca2+ loading, both anesthetics increased the amount of Ca2+ in the SR. The caffeine-induced increase in [Ca2+], was enhanced in the presence of halothane (> or = 1%), enflurane (> or = 1%), and isoflurane (> or = 3%) but was attenuated in the presence of sevoflurane (> or = 3%). The norepinephrine-induced increase in [Ca2+], was enhanced only in the presence of sevoflurane (> or = 3%). Not all of these anesthetic effects on the [Ca2+]i were parallel with the simultaneously observed anesthetic effects on the force. Conclusions In systemic resistance arteries, the halothane, enflurane, isoflurane, and sevoflurane differentially influence the SR functions. Both halothane and enflurane cause Ca2+ release from the caffeine-sensitive SR. In addition, both anesthetics appear to have a stimulating action on Ca2+ uptake in addition to the Ca2+-releasing action. Halothane, enflurane, and isoflurane all enhance, while sevoflurane attenuates, the Ca2+-induced Ca2+-release mechanism. However, only sevoflurane stimulates the inositol 1,4,5-triphosphate-induced Ca2+ release mechanism. Isoflurane and sevoflurane do not stimulate Ca2+ release or influence Ca2+ uptake.

scholarly journals ASIC1 contributes to pulmonary vascular smooth muscle store-operated Ca2+ entry

2009 ◽  
Vol 297 (2) ◽  
pp. L271-L285 ◽  
Author(s):  
Nikki L. Jernigan ◽  
Michael L. Paffett ◽  
Benjimen R. Walker ◽  
Thomas C. Resta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Reactivity ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Arteries ◽  
Cyclopiazonic Acid ◽  
Fura 2 ◽  
Whole Cell Patch Clamp ◽  
Intracellular Ca ◽  
Arterial Constriction

Acid-sensing ion channels (ASIC) are voltage-insensitive, cationic channels that have recently been identified in vascular smooth muscle (VSM). It is possible that ASIC contribute to vascular reactivity via Na+ and Ca2+ conductance; however, their function in VSM is largely unknown. In pulmonary VSM, store-operated Ca2+ entry (SOCE) plays a significant role in vasoregulatory mechanisms such as hypoxic pulmonary vasoconstriction and receptor-mediated arterial constriction. Therefore, we hypothesized that ASIC contribute to SOCE in pulmonary VSM. We examined SOCE resulting from depletion of intracellular Ca2+ stores with cyclopiazonic acid in isolated small pulmonary arteries and primary cultured pulmonary arterial smooth muscle cells by measuring 1) changes in VSM [Ca2+]i using fura-2 indicator dye, 2) Mn2+ quenching of fura-2 fluorescence, and 3) store-operated Ca2+ and Na+ currents using conventional whole cell patch-clamp configuration in voltage-clamp mode. The role of ASIC was assessed by the use of the ASIC inhibitors, amiloride, benzamil, and psalmotoxin 1, or siRNA directed towards ASIC1, ASIC2, or ASIC3 isoforms. We found that store-operated VSM [Ca2+]i responses, Mn2+ influx, and inward cationic currents were attenuated by either pharmacological ASIC inhibition or treatment with ASIC1 siRNA. These data establish a unique role for ASIC1 in mediating SOCE in pulmonary VSM and provide new insight into mechanisms of VSM Ca2+ entry and pulmonary vasoregulation.

Abstract 533: Vascular Smooth Muscle Na/Ca Exchanger-1 Modulates Myogenic Reactivity and Blood Pressure in Chronic Intermittent Hypoxia

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Ling Chen ◽  
Youhua Wang ◽  
Jingyu Wang ◽  
Jin Zhang
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Wall Thickness ◽  
Intermittent Hypoxia ◽  
Vascular Reactivity ◽  
Intraluminal Pressure ◽  
Chronic Intermittent Hypoxia ◽  
Resistance Arteries ◽  
Small Resistance

Chronic intermittent hypoxia (CIH) results in systemic hypertension and altered vascular reactivity in human and rodents. We hypothesize that vascular smooth muscle (VSM) Na/Ca exchanger type-1 (NCX1) is a potential molecular mechanism mediating CIH-induced changes in vascular reactivity and blood pressure (BP). Wild type (WT) and transgenic (TG) mice with VSM-specific NCX1 overexpression were exposed to either CIH (1 min 5% nadir O 2 , followed by 1 min 21% O 2 ; 8 hrs/day for 5 weeks), or normoxia (constant 21% O 2 ). CIH resulted in greater BP elevation in TG (102 ± 3 mm Hg vs. 92 ± 6 mm Hg in normoxia, P < 0.05, n = 6 and 3, measured by intra-carotid artery catheterization under 1.5% isoflurane) than in WT (88 ± 4 mm Hg vs. 83 ± 2 mm Hg in normoxia, NS, n = 3 and 5) mice. Mesenteric small resistance arteries were then isolated and pressurized for diameter and wall thickness measurement. Compared to normoxia controls, CIH-exposed WT arteries exhibited increased resting myogenic tone (21 ± 2% vs. 16 ± 2% of PD in normoxia, P < 0.05, n = 5 each group). Moreover, myogenic reactivity in WT arteries of CIH-exposed mice shifted downward at lower range of intraluminal pressure (20-80 mm Hg), and upward at higher pressure (100-140 mm Hg). The effects of CIH were significantly greater in TG arteries compared to those in WT arteries, suggesting that VSM NCX1 augmented the myogenic response to CIH. Vasoconstrictions induced by phenylephrine (0.003-100 μM), greater in TG arteries, or high (60 mM) external K + solution, were similar between control and CIH groups in the same genotype, suggesting that arterial contractility to agonist stimulation was not affected by CIH. Arterial wall thickness or passive diameters under various intraluminal pressures in Ca 2+ -free solution were not different between control and CIH groups in either genotype, suggesting a lack of arterial stiffness or remodeling. In summary, 1) CIH results in greater BP elevation in TG mice; 2) CIH leads to biphasic changes in myogenic reactivity in small resistance arteries; 3) Overexpression of VSM NCX1 exaggerates BP elevation in CIH, likely by modulating myogenic reactivity, suggesting that VSM NCX1 is a potential mechanism mediating CIH-induced hypertension.

Nickel inhibits endothelin-induced contractions of vascular smooth muscle

1990 ◽  
Vol 258 (6) ◽  
pp. C1025-C1030 ◽  
Author(s):  
K. Blackburn ◽  
R. F. Highsmith
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Porcine Coronary Artery ◽  
Force Development ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Endothelin (ET)-induced contractions of vascular smooth muscle (VSM) are dependent on extracellular Ca2+ yet display only partial sensitivity to L-type Ca2+ antagonists. The purpose of this study was to evaluate the effect of nickel (Ni2+), a Ca2+ channel antagonist with clearly documented differential potency toward L- vs. T-type Ca2+ currents on ET-mediated contractions in VSM. Treatment of rings of left anterior descending porcine coronary artery (LAD) with Ni2+ produced a profound dose-dependent inhibition of isometric force development in response to porcine ET (ET-1). At a concentration of 360 microM, Ni2+ exerted a significant inhibitory effect on contracture in response to doses of ET-1 ranging from 3 to 100 nM. In contrast, the same concentration of Ni2+ failed to significantly affect peak force development in response to KCl depolarization (5-77 mM) or to phenylephrine (0.3-30 mM). In addition, 360 microM Ni2+ significantly inhibited the contractile response of rat aorta to 10 nM ET-1. We conclude that ET-1 activates a Ni2(+)-sensitive process in VSM which may signal an additional Ca2+ influx pathway that appears to be functionally distinct from the L-type Ca2+ channel.

Saline infusion into lumen of resistance artery and small vein causes contraction

1990 ◽  
Vol 259 (1) ◽  
pp. H23-H28 ◽  
Author(s):  
J. A. Bevan ◽  
E. H. Joyce
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Physiological Saline ◽  
Saline Infusion ◽  
Resistance Artery ◽  
Resistance Arteries ◽  
Surface Receptors ◽  
Calcium Dependent ◽  
Rate Dependent ◽  
Physiological Saline Solution

Infusion of saline into the lumen of a resistance artery from the rabbit ear at rates between 0.5 and 20 microliters/min causes a rate-dependent maintained contraction. This contraction is independent of the direction of saline flow and of the endothelium. The contraction is prevented by pretreatment with the vasodilator papaverine (0.1 mM), which also reversed the contraction during flow. Exclusion of calcium from the physiological saline solution plus ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (1 mM) prevents the contraction, as does pre-exposure to cobalt (1 mM) and manganese (1 mM). Both these ions depress saline flow contraction once it is established. Saline flow-dependent contraction changes in a complex manner with temperature. It is greatest in resistance arteries from the pial, ear (skin), and femoral (muscle) segments, moderate to poor in coronary, mesenteric, and renal segments, and absent in the pulmonary segments. A small ear vein adjacent to the ear resistance artery also contracts to saline infusion. Although an explanation based on the washout of a vasodilator metabolite cannot be excluded, we favor the hypothesis that saline flow-induced shear stress of the inner surface of the vessel wall mechanically activates the vascular smooth muscle cells causing an extracellular Ca2(+)-dependent contraction. This response takes place through indomethacin-insensitive calcium-dependent mechanisms in vascular smooth muscle that differ from those associated with commonly studied surface receptors and with stretch.

Depletion and filling of intracellular calcium stores in vascular smooth muscle

1995 ◽  
Vol 268 (2) ◽  
pp. C503-C512 ◽  
Author(s):  
L. A. Blatter
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Surface Membrane ◽  
Membrane Receptors ◽  
Calcium Stores ◽  
Fura 2 ◽  
Vasoactive Substances ◽  
Cytoplasmic Compartment ◽  
A7r5 Cell Line ◽  
Cellular Compartments

In vascular smooth muscle, binding of vasoactive substances to surface membrane receptors leads to a rise of intracellular cytoplasmic Ca2+ and to contraction. Cytoplasmic free Ca2+ concentration ([Ca2+]i) increases through release of Ca2+ from intracellular stores and Ca2+ entry through surface membrane ion channels. Membrane-permeant and membrane-impermeant forms of fura 2 were used to distinguish changes in intracellularly stored Ca2+ ([Ca2+]s) from changes in [Ca2+]i. The spatiotemporal patterns of the movement of Ca2+ between these two cellular compartments in cultured vascular smooth muscle cells (A7r5 cell line) were visualized with digital imaging fluorescence microscopy. The Ca2+ stores were localized by double staining with a fluorescent organelle-specific dye and the Ca2+ indicator. [Ca2+]s was measured after accumulation of the membrane-permeant form of fura 2 inside the stores and quenching of the fura 2 fluorescence in the cytoplasmic compartment with manganese. Stimulation with vasopressin led to a transient increase of [Ca2+]i and a concomitant decrease of [Ca2+]s. After stimulation with vasopressin, [Ca2+]i returned rapidly to normal resting levels, whereas the recovery of [Ca2+]s occurred on a much slower time scale. The refilling pathway of depleted stores involved Ca2+ entry into the bulk cytoplasmic compartment before uptake into the stores.

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