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Effects of sodium metabisulphite on guinea pig contractile airway smooth muscle responses in vitro. 总被引:1,自引:1,他引:0
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BACKGROUND--Sodium metabisulphite (MBS) is known to induce bronchoconstriction in asthmatic patients. The effects of MBS on guinea pig airway smooth muscle and on neurally mediated contraction in vitro have been examined. METHODS--Tracheal and bronchial airway segments were placed in oxygenated buffer solution and electrical field stimulation was performed in the presence of indomethacin (10(-5) M) and propranolol (10(-6) M) for the measurement of isometric tension. Atropine (10(-6) M) was added to bronchial tissues. RESULTS--Concentrations of MBS up to 10(-3) M had no direct effect on airway smooth muscle contraction and did not alter either tracheal smooth muscle contraction induced by electrical field stimulation at all frequencies or acetylcholine-induced tracheal smooth muscle contraction. There was a similar response in the absence of epithelium, except for potentiation of the response induced by electrical field stimulation at 0.5 Hz (24 (10)% increase). However, MBS (10(-5), 10(-6) and 10(-7) M) augmented neurally-mediated non-adrenergic non-cholinergic contractile responses in the bronchi (13.3 (3.2)%, 23.8 (9.6)%, and 6.4 (1.6)%, respectively). MBS had no effect on the contractile response induced by substance P, but at higher concentrations (10(-3) M and 10(-4) M) it caused a time-dependent attenuation of responses induced by either electrical field stimulation or exogenously applied acetylcholine or substance P. CONCLUSIONS--MBS had no direct contractile responses but enhanced bronchoconstriction induced by activation of non-cholinergic neural pathways in the bronchus, probably through increased release of neuropeptides. At high concentrations MBS inhibited contractile responses initiated by receptor or neural stimulation. 相似文献
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Frusemide, an inhibitor of sodium-potassium-chloride (Na-K-Cl) cotransport, has been shown to inhibit the airway response to several constrictor stimuli in asthmatic subjects. The protection seen with frusemide in these studies could be due to an effect on epithelium, inflammatory cells, neural pathways, or airway smooth muscle. To determine whether frusemide inhibits airway smooth muscle contraction, experiments were performed in bovine and human airways in vitro. Fresh bovine tissue was obtained from the abattoir and human tissue from thoracotomy. The effect of 10(-5)M frusemide on histamine, potassium chloride, and hyperosmolar saline induced contractions was studied in bovine tracheal strips without epithelium. Frusemide, at a concentration that specifically inhibits Na-K-Cl cotransport, did not inhibit contraction caused by any of these agents. Frusemide was also without effect on hypertonic saline induced contractions of bovine and human bronchial rings with epithelium intact. These results suggest that modification of Na-K-Cl cotransport does not alter airway smooth muscle contractility and that the protective effect of frusemide on induced bronchoconstriction in vivo is unlikely to be due to a direct effect on airway smooth muscle. 相似文献
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Comparison of in vivo airway responsiveness and in vitro smooth muscle sensitivity to methacholine in man 总被引:5,自引:2,他引:3
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Airway responsiveness to methacholine varies between normal people and is increased in patients with asthma. The importance of airway smooth muscle sensitivity in determining in vivo responsiveness is unknown. We have examined this question by comparing in vivo airway responsiveness with in vitro airway smooth muscle sensitivity to methacholine in 10 patients undergoing thoracic surgery. In vivo responsiveness was determined by administration of inhalations of doubling concentrations of methacholine. Results were expressed as the provocation concentration (PC) causing a decrease in forced expiratory volume in one second of 20% (PC20FEV1), specific airway conductance of 35% (PC35SGaw), and maximal expiratory flow at 35% vital capacity, measured for the partial (V35(p)) and complete (V35(c)) flow volume curves, of 35% (PC35V35(p); PC35V35(c)). In vitro airway smooth muscle sensitivity was determined from specimens obtained at thoracotomy. Log dose-response curves to methacholine were constructed and the concentration causing a 50% maximum contraction (EC50) was derived. There were differences between patients for both in vivo airway responsiveness and in vitro smooth muscle sensitivity to methacholine. There were no significant relationships between the in vivo and in vitro measurements. The results suggest that factors other than solely the sensitivity of smooth muscle must determine in vivo airway responsiveness to methacholine. 相似文献
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BACKGROUND: Halothane relaxes airway smooth muscle, in part, by decreasing the force produced for a given intracellular [Ca(2+)] (i.e., Ca(2+) sensitivity) during muscarinic stimulation, an effect produced by a decrease in regulatory myosin light-chain (rMLC) phosphorylation. The authors tested the hypothesis that halothane reduces rMLC phosphorylation during muscarinic stimulation at constant intracellular [Ca(2+)] by increasing smooth muscle protein phosphatase (SMPP) activity, without changing myosin light-chain kinase (MLCK) activity. METHODS: Enzyme activities were assayed in beta-escin permeabilized strips of canine tracheal smooth muscle. Under conditions of constant intracellular [Ca(2+)], the rate of rMLC phosphorylation was measured by Western blotting during inhibition of SMPP with microcystin-LR (to assay MLCK activity) or during inhibition of MLCK by wortmannin and adenosine triphosphate depletion (to assay SMPP activity). The effect of halothane (0.8 mm) on enzyme activities and isometric force during stimulation with 0.6 microm Ca(2+) and 10 microm acetylcholine was determined. RESULTS: Halothane produced a 14 +/- 8% (mean +/- SD) decrease in isometric force by significantly reducing rMLC phosphorylation (from 32 +/- 9% to 28 +/- 9%). Halothane had no significant effect on any parameter of a monoexponential relation fit to the data for the MLCK activity assay. In contrast, halothane significantly decreased the half-time for rMLC dephosphorylation in the SMPP activity assay (from 0.74 +/- 0.28 min to 0.44 +/- 0.10 min), indicating that it increased SMPP activity. CONCLUSIONS: Halothane decreases Ca(2+) sensitivity and rMLC phosphorylation in airway smooth muscle during muscarinic receptor stimulation by increasing SMPP activity, without affecting MLCK, probably by disrupting receptor G-protein signaling pathways that inhibit SMPP. 相似文献
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M K Ferguson 《The Journal of surgical research》1992,52(4):359-363
The endothelium regulates smooth muscle tone in blood vessels through the release of endothelium-deprived relaxing factor (EDRF). We hypothesized that the lymphatics possess endothelium-dependent relaxant properties analogous to those in blood vessels. Fresh porcine tracheobronchial lymphatic vessel rings were mounted in organ baths and connected to force-displacement transducers. Rings were submaximally precontracted with 10(-5) M histamine and exposed to cumulative addition of acetylcholine (ACH; 10(-7)-3 x 10(-4) M) or bradykinin (BRD; 10(-8)-3 x 10(-6) M), both of which are known to promote release of EDRF. ACH caused concentration-dependent relaxation (maximum effect = -2.3 +/- 2.6% of initial histamine-induced active tension), while a similar but less pronounced effect was seen with BRD (39.6 +/- 5.4%). The relaxant effects of ACH and BRD were inhibited by collagenase pretreatment and mechanical endothelial denudation. The results confirm our hypothesis that lymphatic vessels possess endothelium-dependent relaxant properties and suggest that lymph vessels can regulate lymph flow through processes similar to those found in blood vessels. 相似文献
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BACKGROUND: The investigation examined whether primary alcohols could be used as tools to explore the mechanism of anesthetic actions in airway smooth muscle (ASM). The hypothesis was that, like volatile anesthetics, the primary alcohols relax intact ASM by decreasing intracellular Ca2+ concentration ([Ca2+]i) and by inhibiting agonist-induced increases in the force developed for a given [Ca2+]i (Ca2+ sensitivity). METHOD: The effects of butanol, hexanol, and octanol on isometric force in canine tracheal smooth muscle were examined. The effects of hexanol on [Ca2+]i (measured with fura-2) and the relationship between force and [Ca2+]i were studied during membrane depolarization provided by KCl and during muscarinic stimulation provided by acetylcholine. RESULTS: The primary alcohols relaxed ASM contracted by KCl or acetylcholine in a concentration-dependent manner, with potency increasing as chain length increased. The alcohols could completely relax the strips, even during maximal stimulation with 10 microM acetylcholine (median effective concentrations of 28 +/- 12, 1.3 +/- 0.4, and 0.14 +/- 0.05 mM [mean +/- SD] for butanol, hexanol, and octanol, respectively). Hexanol decreased both [Ca2+]i and force in a concentration-dependent manner. Hexanol decreased Ca2+ sensitivity during muscarinic stimulation but had no effect on the force-[Ca2+]i relationship in its absence. CONCLUSIONS: Primary alcohols produce reversible, complete relaxation of ASM, with potency increasing as chain length increases, by decreasing [Ca2+]i and inhibiting increases in Ca2+ sensitivity produced by muscarinic receptor stimulation. These actions mimic those of volatile anesthetics on ASM, a circumstance suggesting that the primary alcohols may be useful tools for further exploring mechanisms of anesthetic effects on ASM. 相似文献
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BACKGROUND: Chronic airway obstruction is characteristic of cystic fibrosis (CF) but there are few studies of airway smooth muscle remodelling in CF. METHODS: Airway smooth muscle content and mean airway smooth muscle cell size were measured by applying design-based stereology to bronchoscopic biopsy specimens obtained from seven subjects with CF and 15 healthy controls. RESULTS: The smooth muscle content increased by 63% in subjects with CF (mean (SD) 0.173 (0.08) v 0.106 (0.042) mm(3) smooth muscle/mm(3) submucosa, mean difference -0.067; 95% CI -0.12 to -0.013, p = 0.017) but there was no increase in mean cell size (2705 (351) v 2654 (757) microm(3), mean difference -51; 95% CI -687 to 585, p = 0.87). CONCLUSIONS: These findings indicate hyperplasia of airway smooth muscle cells without hypertrophy and suggest that accumulation of airway smooth muscle cells may contribute to airway narrowing and bronchial hyperresponsiveness in CF. 相似文献
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Observations on the smooth muscle and contractile activity of the common bile duct. 总被引:1,自引:1,他引:0
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J R Ludwick 《Annals of surgery》1966,164(6):1041-1050
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利多卡因是临床上常用的局部麻醉药和抗室性心律失常药物;除此之外,利多卡因还具有较强的扩张气道、抑制气道炎症、降低气道高反应性的作用。此方面的研究最早可追溯到上世纪60年代,利多卡因在围术期预防和处理支气管痉挛中所占的地位已得到充分肯定,现将近10余年来利多卡因对气道平滑肌影响的主要研究成果综述如下。 相似文献
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咪唑安定对气管平滑肌舒张作用的研究 总被引:1,自引:0,他引:1
咪唑安定对气管平滑肌有直接舒张作用,作用机制主要和抑制电压依赖性钙通道,降低细胞内钙离子浓度有关;对PKC信号转导系统也有一定的抑制作用;咪唑安定雾化吸入有引起支气管痉挛的可能。 相似文献
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《中华泌尿外科杂志》2009,30(11)
目的 探讨单侧输尿管部分梗阻后输尿管平滑肌超微结构、收缩功能和自律性的改变.方法 Wistar大鼠80只.随机分4组:8周实验组、8周对照组、16周实验组、16周对照组.每组20只.实验组大鼠左侧输尿管上1/2段腰大肌包埋造成单侧输尿管部分梗阻的动物模型,对照组仅分离左侧输尿管.成模后于不同实验点分离大鼠输尿管进行离体肌条实验,测定肌条的收缩幅度和频率的改变,并通过透射电镜观察梗阻后平滑肌超微结构的变化.结果 8周实验组输尿管收缩力和收缩频率分别为(0.62±0.38)g、(18.52±6.70)次/min,8周对照组分别为(0.38±0.36)g、(14.80±4.98)次/min,2组比较差异均有统计学意义(P<0.05).16 周实验组输尿管收缩力和收缩频率分别为(0.15±0.10)g、(12.84±3.32)次/min,16周对照组分别为(0.41±0.38)g、(16.48±3.44)次/min.2组间比较差异均有统计学意义(P<0.05).8周实验组均高于16周实验组(P<0.05),8周对照组与16周对照组比较差异无统计学意义(P>0.05).透射电镜观察到8周实验组平滑肌细胞胞质中线粒体数增多,而16周实验组平滑肌细胞胞质中线粒体数目减少、线粒体肿胀和空泡化、细胞间质中可见大量胶原纤维增生.结论 输尿管梗阻8周的大鼠输尿管肌条自律性和收缩力增加,输尿管平滑肌细胞胞质中线粒体增多,可能是机体代偿所致.输尿管梗阻16周后输尿管平滑肌自律性和收缩力均降低.平滑肌细胞胞质中线粒体数目减少,线粒体肿胀和空泡化,细胞间质中有大量胶原纤维增生,呈失代偿表现. 相似文献