Cigarette smoke-induced bronchoconstriction in dogs: vagal and extravagal mechanisms

1984 ◽  
Vol 57 (4) ◽  
pp. 1261-1270 ◽  
Author(s):  
J. Hartiala ◽  
C. Mapp ◽  
R. A. Mitchell ◽  
R. L. Shields ◽  
W. M. Gold
Keyword(s):  
Smooth Muscle ◽  
Cigarette Smoke ◽  
Airway Smooth Muscle ◽  
Airway Pressure ◽  
Muscle Tone ◽  
Motor Nerve ◽  
Respiratory Center ◽  
Airway Response ◽  
Anesthetized Dogs

We reassessed the severity of cigarette smoke-induced bronchoconstriction and the mechanisms involved in anesthetized dogs. To evaluate the severity of smoke-induced bronchoconstriction, we measured airway pressure and airflow resistance (Rrs, forced oscillation method). We studied the mechanisms in other dogs by measuring airway pressure, central airway smooth muscle tone in tracheal segments in situ, and respiratory center drive by monitoring phrenic motor nerve output, including the role of vagal and extravagal nerves vs. the role of blood-borne materials during inhalation of cigarette smoke. Rrs increased more than fourfold with smoke from one cigarette delivered in two tidal volumes. About half the airway response was due to local effects of smoke in the lungs. The remainder was due to stimulation of the respiratory center, which activated vagal motor efferents to the airway smooth muscle. Of this central stimulation, about half was due to blood-borne materials and the rest to vagal pulmonary afferents from the lungs. We conclude that inhalation of cigarette smoke in dogs causes severe bronchoconstriction which is mediated mainly by extravagal mechanisms.

Nicotine-induced respiratory effects of cigarette smoke in dogs

1985 ◽  
Vol 59 (1) ◽  
pp. 64-71 ◽  
Author(s):  
J. J. Hartiala ◽  
C. Mapp ◽  
R. A. Mitchell ◽  
W. M. Gold
Keyword(s):  
Smooth Muscle ◽  
Cigarette Smoke ◽  
Airway Smooth Muscle ◽  
Direct Effect ◽  
Muscle Tone ◽  
Muscle Tension ◽  
Respiratory Center ◽  
Parasympathetic Ganglia ◽  
Arterial Blood ◽  
Nicotine Receptors

We report that nicotine is responsible for both a blood-borne stimulation of the respiratory center and a direct effect on intrathoracic airway tone in dogs. We introduced cigarette smoke into the lungs of donor dogs and injected arterial blood obtained from them into the circulation of recipient dogs to show that a blood-borne material increased breathing and airway smooth muscle tone. Smoke from cigarettes containing 2.64 mg of nicotine was effective; that from cigarettes containing 0.42 mg of nicotine was not. Nicotine, in doses comparable to the amounts absorbed from smoke, also increased breathing and tracheal smooth muscle tension when injected into the vertebral circulation of recipient dogs. Finally, blockade of nicotine receptors in the central nervous system and in the airway parasympathetic ganglia inhibited the effects of inhaled cigarette smoke and intravenous nicotine on the respiratory center and on bronchomotor tone. We conclude that nicotine absorbed from cigarette smoke is the main cause of cigarette smoke-induced bronchoconstriction. It caused central respiratory stimulation, resulting in increased breathing and airway smooth muscle tension, and had a direct effect on airway parasympathetic ganglia as well.

scholarly journals The role of Eserine and GABA in the activity of DMV on airway smooth muscle tone in ferrets

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Burim Neziri ◽  
Shaip Krasniqi ◽  
Muharrem Jakupaj ◽  
Shqipe Devaja
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Smooth Muscle Tone

Measurement of airway response by isometric and nonisometric techniques in situ

1982 ◽  
Vol 52 (5) ◽  
pp. 1363-1367 ◽  
Author(s):  
A. R. Leff ◽  
N. M. Munoz ◽  
B. Alderman
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Contractile Response ◽  
Muscle Tone ◽  
Dynamic Compliance ◽  
Isometric Tension ◽  
Pulmonary Resistance ◽  
Airway Response ◽  
Anesthetized Dogs

Because isometric systems differ substantially from methods of measuring airway smooth muscle tone that depend on airway diameter, we determined the sensitivity and significance of data derived from these different methods in 20 anesthetized dogs. The airway contractile response was measured directly from an isometric tracheal segment in situ and simultaneously as pulmonary resistance (RL) and dynamic compliance (Cdyn). The contractile response to intravenous (iv) methacholine (MC) (2.6 X 10(-11) to 2.6 X 10(-6) mol/kg) and norepinephrine (NE) (1.2 X 10(-11) to 1.2 X 10(-6) mol/kg) was measured in dose-response studies of beta-blocked and ganglion-blocked animals. A statistically significant change in isometric tracheal tension was first observed at 2.6 X 10(-10) mol/kg iv MC and 1.2 X 10(-9) mol/kg iv NE. Statistically significant changes in Cdyn and RL did not occur at doses less than 10(-8) mol/kg for either agonist. Substantial increase in isometric tracheal tension (greater than 10 g force/cm) occurred before any change in RL or Cdyn. These finding indicate that change in isometric tension reflects parallel changes in RL and Cdyn. For NE and MC, tracheal tension is a more sensitive and selective measurement of airway contraction than RL or Cdyn.

Role for TAK1 in cigarette smoke-induced proinflammatory signaling and IL-8 release by human airway smooth muscle cells

2012 ◽  
Vol 303 (3) ◽  
pp. L272-L278 ◽  
Author(s):  
Tonio Pera ◽  
Claudia Atmaj ◽  
Marieke van der Vegt ◽  
Andrew J. Halayko ◽  
Johan Zaagsma ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Map Kinase ◽  
Cigarette Smoke ◽  
Airway Smooth Muscle ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Dominant Negative ◽  
Airflow Limitation ◽  
Airway Smooth Muscle Cells

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease, characterized by a progressive decline in lung function. Airway smooth muscle (ASM) mass may be increased in COPD, contributing to airflow limitation and proinflammatory cytokine production. Cigarette smoke (CS), the major risk factor of COPD, causes ASM cell proliferation, as well as interleukin-8 (IL-8)-induced neutrophilia. In various cell types, transforming growth factor-β-activated kinase 1 (TAK1) plays a crucial role in MAP kinase and NF-κB activation, as well as IL-8 release induced by IL-1β, TNF-α, and lipopolysaccharide. The role of TAK1 in CS-induced IL-8 release is not known. The aim of this study was to investigate the role of TAK1 in CS-induced NF-κB and MAP kinase signaling and IL-8 release by human ASM cells. Stimulation of these cells with CS extract (CSE) increased IL-8 release and ERK-1/2 phosphorylation, as well as Iκ-Bα degradation and p65 NF-κB subunit phosphorylation. CSE-induced ERK-1/2 phosphorylation and Iκ-Bα degradation were both inhibited by pretreatment with the specific TAK1 inhibitor LL-Z-1640-2 (5Z-7-oxozeaenol; 100 nM). Similarly, expression of dominant-negative TAK1 inhibited CSE-induced ERK-1/2 phosphorylation. In addition, inhibitors of TAK1 and the NF-κB (SC-514; 50 μM) and ERK-1/2 (U-0126; 3 μM) signaling inhibited the CSE-induced IL-8 release by ASM cells. These data indicate that TAK1 plays a major role in CSE-induced ERK-1/2 and NF-κB signaling and in IL-8 release by human ASM cells. Furthermore, they identify TAK1 as a novel target for the inhibition of CS-induced inflammatory responses involved in the development and progression of COPD.

scholarly journals A-kinase-anchoring proteins coordinate inflammatory responses to cigarette smoke in airway smooth muscle

2015 ◽  
Vol 308 (8) ◽  
pp. L766-L775 ◽  
Author(s):  
Wilfred J. Poppinga ◽  
Irene H. Heijink ◽  
Laura J. Holtzer ◽  
Philipp Skroblin ◽  
Enno Klussmann ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cigarette Smoke ◽  
Airway Smooth Muscle ◽  
Lung Tissue ◽  
Inflammatory Responses ◽  
Camp Signaling ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Anchoring Proteins

β2-Agonist inhibitors can relieve chronic obstructive pulmonary disease (COPD) symptoms by stimulating cyclic AMP (cAMP) signaling. A-kinase-anchoring proteins (AKAPs) compartmentalize cAMP signaling by establishing protein complexes. We previously reported that the β2-agonist fenoterol, direct activation of protein kinase A (PKA), and exchange factor directly activated by cAMP decrease cigarette smoke extract (CSE)-induced release of neutrophil attractant interleukin-8 (IL-8) from human airway smooth muscle (ASM) cells. In the present study, we tested the role of AKAPs in CSE-induced IL-8 release from ASM cells and assessed the effect of CSE on the expression levels of different AKAPs. We also studied mRNA and protein expression of AKAPs in lung tissue from patients with COPD. Our data show that CSE exposure of ASM cells decreases AKAP5 and AKAP12, both capable of interacting with β2-adrenoceptors. In lung tissue of patients with COPD, mRNA levels of AKAP5 and AKAP12 were decreased compared with lung tissue from controls. Using immunohistochemistry, we detected less AKAP5 protein in ASM of patients with COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II compared with control subjects. St-Ht31, which disrupts AKAP-PKA interactions, augmented CSE-induced IL-8 release from ASM cells and diminished its suppression by fenoterol, an effect mediated by disturbed ERK signaling. The modulatory role of AKAP-PKA interactions in the anti-inflammatory effects of fenoterol in ASM cells and the decrease in expression of AKAP5 and AKAP12 in response to cigarette smoke and in lungs of patients with COPD suggest that cigarette smoke-induced changes in AKAP5 and AKAP12 in patients with COPD may affect efficacy of pharmacotherapy.

scholarly journals Chloride in airway smooth muscle: the ignored anion no longer?

2012 ◽  
Vol 302 (8) ◽  
pp. L733-L735 ◽  
Author(s):  
George Gallos ◽  
Peter Yim ◽  
Charles W. Emala
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Calcium Handling ◽  
Muscle Physiology ◽  
Smooth Muscle Contractility ◽  
Chloride Currents ◽  
New Developments ◽  
Mediated Effects

This Perspectives accompanies an Editorial Focus that summarizes new developments concerning the role of chloride in airway smooth muscle physiology. We provide several observations and mechanistic insights to reconcile recent experimental evidence with existing paradigms concerning chloride channel-mediated effects on airway smooth muscle tone. In addition, we highlight the potentially complex and dynamic nature that chloride currents and membrane potential have on calcium handling and airway smooth muscle contractility.

Tracheal smooth muscle responses to upper airway pressure in conscious dogs

1990 ◽  
Vol 68 (4) ◽  
pp. 1555-1561 ◽  
Author(s):  
L. Plowman ◽  
P. H. Edwards ◽  
D. C. Lauff ◽  
M. Berthon-Jones ◽  
C. E. Sullivan
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Pressure ◽  
Breathing Pattern ◽  
Muscle Tone ◽  
Upper Airway ◽  
Tracheal Smooth Muscle ◽  
Smooth Muscle Tone ◽  
Pressure Stimulus ◽  
Tracheal Stoma

We studied the influence of changes in pressure applied to the isolated upper airway of four conscious dogs on tracheal smooth muscle tone and breathing pattern. The dogs were prepared with a permanent side-hole tracheal stoma and were trained to sleep with a snout mask hermetically sealed in place while breathing through a cuffed endotracheal tube inserted distally into the tracheal stoma. Changes in tracheal smooth muscle tone were continuously monitored by measuring the pressure in the water-filled cuff that distended the tracheal airway while pressure changes were introduced in the upper airway independently of breathing. Increases or decreases of upper airway pressure (+/- 10 cmH2O) had little effect on tracheal airway smooth muscle tone. In contrast, an oscillating pressure wave at 30 Hz and +/- 3 cmH2O amplitude (or -3 to -7 cmH2O amplitude) caused a marked increase in tracheal airway smooth muscle tone. An elevated tracheal airway tone could be maintained over many minutes when the oscillating pressure stimulus was pulsed so that there was a cycle of 0.5 s on, 0.5 s off. This stimulus did not change the functional residual capacity but resulted in coughing, swallowing, or sighing in 54% of the tests. In the remaining tests, the pressure stimulus produced a rapid, shallow, and erratic breathing pattern. The tracheal airway constrictor response (but not the ventilatory response) was completely abolished by intravenous atropine. We suggest that upper airway vibration is a potentially powerful mechanism of reflex airway smooth muscle constriction.

Invited Review: Complexity of factors modulating airway narrowing in vivo: relevance to assessment of airway hyperresponsiveness

2003 ◽  
Vol 95 (3) ◽  
pp. 1305-1313 ◽  
Author(s):  
Vito Brusasco ◽  
Riccardo Pellegrino
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Activation ◽  
Muscle Tone ◽  
Clinical Settings ◽  
Airway Narrowing ◽  
Geometric Factors ◽  
Airway Caliber ◽  
Airway Response

In vivo, the airway response to constrictor stimuli is the net result of a complex array of factors, some facilitating and some opposing airway narrowing, which makes the interpretation of bronchial challenges far from being straightforward. This review begins with a short description of the complex mechanisms of airway smooth muscle activation and force generation as the starting events for airway narrowing. It then focuses on gain factors modulating airway smooth muscle shortening and on the geometric factors determining the magnitude of reduction in airway caliber in vivo. Finally, in light of the evidence that mechanical modulation of airway smooth muscle tone and airway narrowing is at least as important as the inflammatory contractile mediators in the pathogenesis of airway hyper-responsiveness, the implications for the interpretation of bronchial challenges in clinical settings are discussed.

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