Effects of Midazolam on Intracellular Calcium sup 2+ and Tension in Airway Smooth Muscles

Yoshimura, Hayashi; Kai, Tetsuya; Nishimura, Junji; Kobayashi, Sei; Takahashi, Shosuke; Kobayashi, Hideo

doi:10.1097/00000542-199511000-00015

Cited by 25 publications

(16 citation statements)

References 31 publications

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“…During the 1 h post‐fura‐PE3 loading equilibration period, the strips were stimulated with 40 m M K + PSS at 5 – 10 min intervals, and the muscle length was increased in a stepwise manner after each stimulation until the developed tension reached a maximum. When exposed to 40 m M K + PSS, most strips produced a stable tension within 15 min, with or without an initial transient force response ( Kai et al ., 1993 ; 1996 ; Yoshimura et al ., 1995 ). Any strips showing instability in tension, as induced by 40 m M K + PSS, were excluded from the study.…”

Section: Methodsmentioning

confidence: 99%

Leukotriene C₄ enhances the contraction of porcine tracheal smooth muscle through the activation of Y‐27632, a rho kinase inhibitor, sensitive pathway

Setoguchi

Nishimura

Hirano

et al. 2001

British J Pharmacology

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1 An unsaturated fatty acid, leukotriene C 4 (LTC 4 ), has a potent contractile eect on human airway smooth muscle, and has been implicated in the pathogenesis of human asthma. Using frontsurface¯uorometry with fura-PE3, the eect of LTC 4 on the intracellular Ca 2+ concentration ([Ca 2+ ] i ) and tension were investigated in porcine tracheal smooth muscle strips. 2 The application of LTC 4 induced little or no contraction despite a small and transient increase in [Ca 2+ ] i . In the presence of LTC 4 , however, the contractions evoked by high K + depolarization or a low concentration of carbachol (CCh) were markedly enhanced without inducing any changes in the [Ca 2+ ] i levels, thus indicating that LTC 4 increases the Ca 2+ responsiveness of the contractile apparatus. This LTC 4 -induced increase in Ca 2+ responsiveness could partly be reproduced in the permeabilized preparation of tracheal smooth muscle strips. 3 The LTC 4 -induced enhancement of contraction was accompanied by an increase in myosin light chain (MLC) phosphorylation and was blocked by a rho kinase inhibitor (Y-27632), but not by either a PKC inhibitor (calphostin C) or a tyrosine kinase inhibitor (genistein). 4 These results indicated that, in porcine tracheal smooth muscle, LTC 4 enhances the contraction by increasing the Ca 2+ responsiveness of the contractile apparatus in a MLC phosphorylation dependent manner, possibly through the activation of the rho-rho kinase pathway.

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Section: Methodsmentioning

confidence: 99%

Leukotriene C₄ enhances the contraction of porcine tracheal smooth muscle through the activation of Y‐27632, a rho kinase inhibitor, sensitive pathway

Setoguchi

Nishimura

Hirano

et al. 2001

British J Pharmacology

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“…However, the mechanism by which midazolam exerts bronchodilating effects has not been clearly defined. It has been reported that GABA inhibits postganglionic cholinergic neurotransmission is and, thus, the spasmolytic effect might be due to GABA receptor activation by midazolam bound to benzodiazepine 4 found that midazolam relaxed K § and carbachol-induced contraction of airway smooth muscle in accordance with a decrease in intracellular calcium by inhibition of the influx of extracellular Ca 2+, and that central and peripheral benzodiazepine antagonist could not reverse the relaxation. Therefore, voltage sensitive Ca 2 § channels may be involved in the mechanism.…”

Section: Discussionmentioning

confidence: 96%

“…However, in vivo its effect has not been studied. [2][3][4] Airway calibre is normally assessed indirectly by measuring airway resistance or compliance, which can be strongly influenced by airway secretions. 5 However, there are several reports of the relative insensitivity of indirect measurements of airway calibre.…”

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confidence: 99%

Midazolam reverses histamine-induced bronchoconstriction in dogs

et al. 1997

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Purpose: Midazolam has been used clinically as a sedative and as an anaesthetic induction agent. However, the bronchodilating effects of midazolam have not been comprehensively evaluated. We sought to determine relaxant effects of midazolam on the ai~ay.Methods: After our Animal Care Committee approved the study, eight mongrel dogs were anaesthetized w~h 30 mg.kg ~ pentobarb~one/v, and were paralysed with 200 yg.kg -~ .hr ~ pancuronium. The trachea was intubated with an endotracheal tube (ID 7 mm) that had a second lumen for insertion of a superfine fibreoptic bronchoscope (OD 2.2 mm) to measure the bronchial cross-sectional area (BCA) continuously. The tip of the bronchoscope was placed at the level of the second or third bronchial bifurcation of the right bronchus. A videoprinter printed the BCA which was then measured with a NIH Image program. Bronchoconstriction was produced with histamine (H) 10/Jg-kg ~ followed by 500/~g.kg ~-hr -~. Thirty minutes later, 0 [saline], 0.01,0. I and 1.0 mg.kg ~ midazolam and 25/~g.kg -~ flumazenil were given. The BCA was assessed before (basal area) and 30 min after the start of H infusion, and was also measured f~e minutes after each midazolam and flumazenil/v. At the same time, arterial blood was sampled for plasma catecholamine measurement. Results: Histamine infusion decreased BCA to 49.7 + 17.3% of basal BCA. More than O. I mg'kg ~ midazolam increased BCA up to 71.7 _+ 15.3% of the basal (I .0 mg'kg -~) (P < 0.01). Plasma adrenaline concentration was decreased from 6.9 -+ 3.8 to 3.7 -+ 1.9 ng.ml -~ by 1.0 mg.kg ~ midazolam (P < 0.05). Flumazenil did not antagonize the relaxant effect of midazolam but reversed the inhibitory effect of midazolam on histamine-induced adrenaline release. Conclusion: Midazolam has a sp~moly~c effect on constricted airways but this bronchodilatatJon was not reversed by flumazenil.Objectif : En clinique, on utilise le midazolam comme s6datif et comme agent d'induction de I'anesth6sie. Cependant, les effets bronchodilatateurs du midazolam n'ont jamais fair I'objet d'une 6valuation complete. Nous avons recherch6 tes effets relaxants du midazolam sur les voles a~riennes. M~thodes : Apr~s I'approbation du comit6 d'exp~rimentation animale, huit chiens de race commune ont ~t6 anesth6si6s avec 30 mg'kg ~ de pentobarbital iv et paralys6s avec 200/Jg'kg-~'h -~ de pancuronium. La trach6e a 6t6 intub6e avec un tube endotrach6al (DI 7 mm) avec une deuxi~me lumi~re pour I'insertion d'un bronchofibroscope extra-fin (DE 2,2 mm) pour la mesure de la surface transversale bronchique (STB) en continu. !~extr~mit6 du bronchoscope a 6t6 plac6e au niveau de la deuxi~me ou troisi~me bifurcation de la bronche droite. Une imprimante vid6o imprimait la mesure de la STB avec un programme d'imagerie du NIH. La bronchoconstriction 6tait provoqu6e avec de I'histamine (H) I0/lg'kg ' suivie d'une perfusion de 500/~gkg L-h '. Trente minutes plus tard, on administrait 0 mg, O, 01 mg, 0, I mg et 1,0 mg.kg-' de midazolam et 25/~g-kg ~ de flumaz6nil. La STB ~tait 6valu6e avant (su...

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“…13,14 In astrocytes, however, there is evidence that the opposite is true. 15 Furthermore, because an increase in intracellular Ca 2+ is often responsible for the neurotoxicity associated with receptor activation, we assessed the impact of midazolam on intracellular Ca 2+ in DRG neurons.…”

Section: Midazolam-induced Increase In Intracellular Ca 2+mentioning

confidence: 99%

Mechanisms Underlying Midazolam-Induced Peripheral Nerve Block and Neurotoxicity

Yılmaz

Hough

Gebhart

et al. 2014

Regional Anesthesia and Pain Medicine

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Effects of Midazolam on Intracellular Calcium sup 2+ and Tension in Airway Smooth Muscles

Cited by 25 publications

References 31 publications

Leukotriene C₄ enhances the contraction of porcine tracheal smooth muscle through the activation of Y‐27632, a rho kinase inhibitor, sensitive pathway

Leukotriene C₄ enhances the contraction of porcine tracheal smooth muscle through the activation of Y‐27632, a rho kinase inhibitor, sensitive pathway

Midazolam reverses histamine-induced bronchoconstriction in dogs

Mechanisms Underlying Midazolam-Induced Peripheral Nerve Block and Neurotoxicity

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Effects of Midazolam on Intracellular Calcium sup 2+ and Tension in Airway Smooth Muscles

Cited by 25 publications

References 31 publications

Leukotriene C4 enhances the contraction of porcine tracheal smooth muscle through the activation of Y‐27632, a rho kinase inhibitor, sensitive pathway

Leukotriene C4 enhances the contraction of porcine tracheal smooth muscle through the activation of Y‐27632, a rho kinase inhibitor, sensitive pathway

Midazolam reverses histamine-induced bronchoconstriction in dogs

Mechanisms Underlying Midazolam-Induced Peripheral Nerve Block and Neurotoxicity

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Leukotriene C₄ enhances the contraction of porcine tracheal smooth muscle through the activation of Y‐27632, a rho kinase inhibitor, sensitive pathway

Leukotriene C₄ enhances the contraction of porcine tracheal smooth muscle through the activation of Y‐27632, a rho kinase inhibitor, sensitive pathway