Effect of Mechanical Length Oscillations on Airways Smooth Muscle Reactivity and Crossbridge Cycling

Author(s):  
P. Mbikou ◽  
A. M. Al-Jumaily

Superimposition of length fluctuations on contracted ASM have shown to reduce active force and stiffness. This effect is usually attributed to disruption of the actomyosin crossbridge cycle; however no direct experimental data is available to support this hypothesis. This in vitro study investigated the effect of the mechanical strains on 1) the ASM reactivity and 2) on the actin-myosin crossbridges. Experiments were carried out on maximally contracted bovine ASM subjected to length strains at various frequency in the range from 10 to 100Hz, superimposed on normal tidal stretches (frequency 0.33Hz, amplitude 4%). An organ bath system was used to apply strains and measure the force; immunofluorescence technique was performed to assess the crossbridges. The results show that superimposed length strains increase breathing relaxation effect with an optimal effect obtained at 50Hz. The cholinergic stimulation promotes actin-myosin connection, and length stretches promote the detachment of those crossbridges.

2002 ◽  
Vol 97 (6) ◽  
pp. 1491-1499 ◽  
Author(s):  
Michael K. Herbert ◽  
Susanne Roth-Goldbrunner ◽  
Peter Holzer ◽  
Norbert Roewer

Background Inhibition of intestinal peristalsis is a major side effect of drugs used for anesthesia or for analgesia and sedation of patients in the intensive care unit. This in vitro study examined the effect of clonidine and dexmedetomidine on intestinal peristalsis and analyzed some of their mechanisms of action. Methods In isolated segments of the guinea pig small intestine, peristalsis was triggered by a perfusion-induced rise of the intraluminal pressure. The peristaltic pressure threshold to elicit a peristaltic wave was used to quantify drug effects on peristalsis. Vehicle (Tyrode's solution), clonidine (10 nM-100 microm), or dexmedetomidine (0.1-100 nM) were added extraserosally to the organ bath. In other series of experiments, clonidine or dexmedetomidine was administered after pretreatment with yohimbine, prazosin, apamin, naloxone, or vehicle. Clonidine was also tested after blockade of NO synthase with L-NAME and in the presence of the inactive enantiomer D-NAME. Results Clonidine and dexmedetomidine concentration-dependently increased peristaltic pressure threshold and inhibited peristalsis (clonidine: EC50 = 19.6 microm; dexmedetomidine: EC50 = 12.0 nM). The inhibition caused by clonidine could be prevented by pretreatment with yohimbine, naloxone, and apamin, but not by prazosin, L-NAME, or D-NAME. Inhibition caused by dexmedetomidine was prevented by yohimbine only.(50) (50) Conclusions The results reveal that clonidine and, much more potently, dexmedetomidine inhibit peristalsis of the guinea pig ileum. The inhibition is caused by interaction with alpha2 adrenoceptors and, in the case of clonidine, also involves activation of small conductance Ca2+ -activated potassium channels and endogenous opioidergic pathways.


Author(s):  
Rashmi Prakash ◽  
Vinay Singh ◽  
Devesh Kumar ◽  
Jamal Haider ◽  
A. B. Asthana ◽  
...  

Background: The small intestine, like the rest of the gastrointestinal tract, is an intelligent organ. It generates a wide variety of motor patterns to meet motility requirements in different situations. Its basic motor function after a meal is to mix the chyme with exocrine and intestinal secretions, agitate its contents too.Methods: In vitro study is done to explore the effect of 1st generation antihistaminic (chlorpheniramine maleate) and second generation antihistaminic (Fexofenadine) on amplitude of gut motility by isolated rabbit gut preparation on Dale’s Organ bath, part of terminal ileum is used for study. Eight rabbits weighing 2 to 4.5 kg were used for study. The effect of antihistaminic observed that both drugs reduce amplitude.Results: The effect of Chlorpheniramine malete and Fexofenadine on amplitude observed and it found that both decrease the amplitude significantly.Conclusions: This study establishes a correlation between amplitude of gut and effect of antihistaminic suggests that antihistaminic drug both first generation and second generation decreases the amplitude of gut motility with a significant response.


2018 ◽  
Vol 1 (1) ◽  
pp. 320-330
Author(s):  
Erikson Sinaga ◽  
Nahitma Ginting ◽  
Edy Suwarso

Titanus (Leea aequata L.) merupakan tumbuhan dari suku leeaceae yang digunakan dalam pengobatan tradisional di daerah Tanah Karo, Provinsi Sumatera utara, sebagai obat luka dan obat anti tetanus. Salah satu tanda utama dari penyakit tetanus adalah spasme otot atau kejang disebagian atau seluruh tubuh. Penelitian ini bertujuan untuk mengetahui efek antikejang berupa relaksasi dari ekstrak etanol daun titanus terhadap kontraksi ileum marmut terisolasi yang dikontrasikan dengan asetilkolin. Penelitian ini dilakukan secara in vitro menggunakan alat organ bath. Tahapan penelitian adalah persiapan bahan dan pengujian efek relaksasi ileum terpisah. Parameter yang diukur dalam penelitian ini adalah relaksasi otot polos ileum terpisah. Sebelum dilakukan pengujian, ileum marmut terpisah diekuilibrasi selama 45 menit sampai diperoleh kondisi yang stabil didalam larutan tyrode dengan suhu 37o C yang diaerasi dengan gas karbogen (O2:CO2) 95% : 5%. Pengujian efek relaksasi dilakukan setelah ileum marmut dikontraksi dengan asetilkolin, kemudian masing masing ileum diberikan konsentrasi kumulatif ekstrak daun titanus dan atropin sulfat . Hasil pengujian yang diperoleh menunjukkan bahwa pemberian ekstrak etanol daun titanus memiliki efek relaksasi. Ekstrak etanol daun titanus pada konsentrasi 2,5mg/ml (105,4203±2,9151) mempunyai kemampuan yang tidak berbeda dengan atropin sulfat 1 x 10-5 (113,9796±4,5825) dalam menurunkan kontraksi otot polos ileum yang diinduksi oleh asetilkolin 1,889 x 10-4 M (p>0,005). Jadi dapat disimpulkan bahwa ekstrak etanol daun titanus mempunyai efek relaksasi terhadap otot polos ileum terpisah dengan kemampuan yang tidak jauh berbeda dengan atropin sulfat. Titanus (Leeaaequata L.) is a plant from Leeaceae family used in traditional medication in Tanah Karo, North Sumatera as wound and anti-tetanus medicine. One of the main signs of tetanus is muscle spasm or seizure in some or all parts of body. This research aimed to evaluatethe anti-seizure effect of titanus leaves ethanol extractsuch as relaxation isolated ileum of marmot which was contacted with acetylcholine. This research was conducted byin vitro studyusing organ bath instrument. The stages of this research were the material preparation and isolated ileum relaxation effect evaluation. The parameter measured in this research was the isolated ileum smooth muscle relaxation. Before the test, isolated marmot ileum was equilibrated for 45 minutes until the stable condition in tyrode solution was obtained at 37°C temperature which aerated with carbogen gas (O2:CO2) 95%:5%. The relaxation effect test was conducted aftermarmot ileum was contracted with acetylcholine, and then, titanus leaves extract and atropine sulfate were added to each ileumswith cumulative concentration. The result indicated that the titanus leaves ethanol extract had relaxation effect. Titanus Leaves ethanol extract in 2.5 mg/ml concentration (105.4203±2.9151) had the same ability as atropine sulfate 1x10-5 (113.9796±4.5825)in decreasing the ileum smooth muscle contraction induced with acetylcholine 1.889x10-4 M (p>0.005).It could be concluded that titanus leaves ethanol extract hasrelaxation effect to isolated ileum smooth muscle and it was not so different with atropine sulfate.


2012 ◽  
Vol 49 (No. 11) ◽  
pp. 401-405
Author(s):  
H. Ocal ◽  
M. Yuksel ◽  
A. Ayar

The aim of this study was to investigate the effects of gentamycin on KCl-induced contractions of myometrium isolated from both non-pregnant and pregnant cows. Myometrial strips were isolated from non-pregnant and pregnant cows and suspended in a jacketed organ bath filled with Krebs&rsquo; solution at 37&deg;C (pH 7.4) continuously bubbled with 95% oxygen and 5% carbon dioxide; isometric contractions were recorded using an isometric force displacement transducer. After manifestation of spontaneous contractions, KCl (60 mM) was applied to the bath and the effects of gentamycin (300 &micro;M, 600 &micro;M) on the amplitude (g) and frequency of KCl-induced contractions were evaluated in 10-minute intervals. Data were statistically analysed using Student&rsquo;s t-test and Wilcoxon signed-rank test. Gentamycin inhibited the frequency and amplitude of KCl-induced contractions in a concentration dependent manner. At 300 &micro;M and 600 &micro;M, gentamycin significantly inhibited the amplitude and reduced the frequency of contractions of myometrium isolated from both pregnant and non-pregnant cows. However, an increase in the extracellular Ca<sup>+</sup> ion concentration virtually reversed this blockade. The results of this in vitro study indicate that gentamycin inhibits KCl-induced contractions of myometrium isolated from both non-pregnant and pregnant cows.


1988 ◽  
Vol 255 (6) ◽  
pp. H1391-H1398 ◽  
Author(s):  
T. J. Kulik ◽  
J. N. Evans ◽  
W. J. Gamble

Stretch stimulates contraction of systemic blood vessels, but the response has not been described in pulmonary vessels. To determine whether pulmonary arteries contract when stretched, isolated cylindrical segments of pulmonary arteries were suspended between two parallel wires, stretched, and the active force was generated in response to stretch measured. Eighty-nine percent of segments from small (in situ diameter less than 1,000 microns) feline pulmonary arteries contracted when stretched, and in 65% of these the magnitude of stretch was related to the magnitude of contraction. Large (in situ diameter greater than or equal to 1,000 microns) feline pulmonary arteries did not contract with stretch. Multiple, rapidly repeated stretches resulted in a diminution of active force development. Stretch-induced contraction required external Ca2+ and was abolished by diltiazem (10 microns), but it was not affected by phenoxybenzamine, phentolamine, diethylcarbamazine, or mechanical removal of endothelium. Indomethacin blunted but did not abolish stretch-induced contraction, an effect that may have been nonspecific. This study suggests that stretch can act, probably directly, on smooth muscle in small feline pulmonary arteries to elicit contraction and that it may be a determinant of pulmonary vascular tone. In addition, feline pulmonary arteries are suitable for the in vitro study of stretch-induced contraction.


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