Airway smooth muscle responsiveness from dogs with airway hyperresponsiveness after O3 inhalation

1988 ◽  
Vol 65 (1) ◽  
pp. 57-64 ◽  
Author(s):  
G. L. Jones ◽  
P. M. O'Byrne ◽  
M. Pashley ◽  
R. Serio ◽  
J. Jury ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Potassium Chloride ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Trachealis Muscle

Airway hyperresponsiveness occurs after inhalation of O3 in dogs. The purpose of this study was to examine the responsiveness of trachealis smooth muscle in vitro to electrical field stimulation, exogenous acetylcholine, and potassium chloride from dogs with airway hyperresponsiveness after inhaled O3 in vivo and to compare this with the responsiveness of trachealis muscle from control dogs. In addition, excitatory junction potentials were measured with the use of single and double sucrose gap techniques in both groups of dogs to determine whether inhaled O3 affects the release of acetylcholine from parasympathetic nerves in trachealis muscle. Airway hyperresponsiveness developed in all dogs after inhaled O3 (3 ppm for 30 min). The acetylcholine provocative concentration decreased from 4.11 mg/ml before O3 inhalation to 0.66 mg/ml after O3 (P less than 0.0001). The acetylcholine provocative concentration increased slightly after control inhalation of dry room air. Airway smooth muscle showed increased responses to both electrical field stimulation and exogenous acetylcholine but not to potassium chloride in preparations from dogs with airway hyperresponsiveness in vivo. The increased response to electrical field stimulation was not associated with a change in excitatory junctional potentials. These results suggest that a postjunctional alteration in trachealis muscle function occurs after inhaled O3 in dogs, which may account for airway hyperresponsiveness after O3 in vivo.

Effects of elastic loading on porcine trachealis muscle mechanics

1990 ◽  
Vol 69 (3) ◽  
pp. 1033-1039 ◽  
Author(s):  
K. Ishida ◽  
P. D. Pare ◽  
T. Blogg ◽  
R. R. Schellenberg
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Length ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Elastic Loading ◽  
Trachealis Muscle

To shorten in vivo, airway smooth muscle must overcome an elastic load provided by cartilage and lung parenchyma. We examined the effects of linear elastic loads (0.2-80 g/cm) on the active changes in porcine trachealis muscle length and tension in response to electrical field stimulation in vitro. Increasing elastic loads produced an exponential decrease in the shortening and velocity of shortening while causing an increase in tension generation of muscle strips stimulated by electrical field stimulation. Shortening was decreased by 50% at a load of 8 g/cm. At small elastic loads (less than or equal to 1 g/cm) contractile responses approximated isotonic responses (shortening approximately 60% of starting length), whereas at large loads (20 g/cm) responses approximated isometric responses with minimal shortening (20%). We conclude that elastic loading significantly alters the mechanical properties of airway smooth muscle in vitro, effects that are likely relevant to the loads against which the smooth muscle must contract in vivo.

Release of epithelium-derived PGE2 from canine trachea after antigen inhalation

1998 ◽  
Vol 274 (2) ◽  
pp. L220-L225 ◽  
Author(s):  
I. McGrogan ◽  
L. J. Janssen ◽  
J. Wattie ◽  
P. M. O’Byrne ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Tracheal Smooth Muscle ◽  
Organ Bath ◽  
Field Stimulation ◽  
Electrical Field ◽  
Concentration Response Curve

To investigate the role of prostaglandin (PG) E2 in allergen-induced hyperresponsiveness, dogs inhaled either the allergen Ascaris suum or vehicle (Sham). Twenty-four hours after inhalation, some animals exposed to allergen demonstrated an increased responsiveness to acetylcholine challenge in vivo (Hyp-Resp), whereas others did not (Non-Resp). Strips of tracheal smooth muscle, either epithelium intact or epithelium denuded, were suspended on stimulating electrodes, and a concentration-response curve to carbachol (10−9 to 10−5 M) was generated. Tissues received electrical field stimulation, and organ bath fluid was collected to determine PGE2content. With the epithelium present, all three groups contracted similarly to 10−5 M carbachol, whereas epithelium-denuded tissues from animals that inhaled allergen contracted more than tissues from Sham dogs. In response to electrical field stimulation, Hyp-Resp tissues contracted less than Sham tissues in the presence of epithelium and more than Sham tissues in the absence of epithelium. PGE2release in the muscle bath was greater in Non-Resp tissues than in Sham or Hyp-Resp tissues when the epithelium was present. Removal of the epithelium greatly inhibited PGE2release. We conclude that tracheal smooth muscle is hyperresponsive in vitro after in vivo allergen exposure only when the modulatory effect of the epithelium, largely through PGE2 release, is removed.

Allergen-induced airway hyperresponsiveness in Brown-Norway rat: role of parasympathetic mechanisms

1993 ◽  
Vol 75 (1) ◽  
pp. 279-284 ◽  
Author(s):  
W. Elwood ◽  
T. Sakamoto ◽  
P. J. Barnes ◽  
K. F. Chung
Keyword(s):  
Airway Hyperresponsiveness ◽  
Allergen Challenge ◽  
Electrical Field Stimulation ◽  
Airway Responsiveness ◽  
Brown Norway ◽  
Field Stimulation ◽  
Electrical Field ◽  
Norway Rat

Enhanced parasympathetic mechanisms may contribute to airway hyperresponsiveness. The present study examined whether the in vivo increase in airway responsiveness seen 18–24 h after either a single or chronic aerosolized allergen challenge protocol in actively sensitized Brown-Norway rats was due to altered parasympathetic mechanisms. The roles of central and reflex vagal mechanisms were studied by performing bilateral cervical vagotomy before measurement of airway responsiveness. Bilateral vagotomy failed to reduce the increase in airway responsiveness after either a single or chronic allergen challenge. The roles of increased neural release of acetylcholine (ACh) and increased end organ responsiveness were studied in vitro. The isometric responses of tracheal and bronchial strips to both electrical field stimulation and exogenously applied ACh from rats exposed both to single and chronic allergen challenges were compared with those from saline-exposed rats. The responses to electrical field stimulation and to exogenous ACh were not significantly enhanced 18–24 h after either protocol. We conclude that the airway hyperresponsiveness observed in this allergic rat model is not mediated through an enhancement of parasympathetic mechanisms.

Myogenic and neurogenic mechanisms and arachidonate metabolites in bronchial muscle response to allergen

1997 ◽  
Vol 273 (6) ◽  
pp. L1118-L1125 ◽  
Author(s):  
L. J. Janssen ◽  
I. McGrogan ◽  
J. Wattie ◽  
P. M. O’Byrne ◽  
E. E. Daniel
Keyword(s):  
Airway Hyperresponsiveness ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Muscle Response ◽  
Arachidonate Metabolites ◽  
Evoked Contractions ◽  
Bathing Fluid

We investigated allergen-induced airway hyperresponsiveness (AH) in bronchial tissues obtained from dogs that inhaled Ascaris suum leading to AH (RESP) in vivo or that exhibited no change (NON-RESP) as well as from dogs that inhaled saline (SHAM). RESP tissues were not hyperresponsive to KCl or to carbachol, whereas contractions to electrical field stimulation (EFS) were reduced. This reduction was reversed partially by indomethacin and completely by replacement of the bathing fluid. Radioimmunoassay revealed marked elevation of prostaglandin (PG) E2 generation in RESP tissues compared with SHAM and NON-RESP tissues. EFS-evoked contractions were often followed by a slowly developing secondary contraction in RESP tissues but not in SHAM or NON-RESP tissues. However, indomethacin unmasked such secondary contractions in many SHAM and NON-RESP tissues and markedly enhanced those in RESP tissues, whereas L-655,240 (thromboxane A2/PGD2receptor antagonist) abolished such contractions in all groups. We were unable to detect thromboxane using radioimmunoassay. We conclude that allergen-induced AH involves altered generation of cyclooxygenase metabolites of arachidonic acid (particularly PGE2) as well as of a nonprostanoid inhibitory factor; as such, the responsiveness of the tissue in vitro is dependent on the relative levels of inhibitory and excitatory metabolites.

Cholinergic neuromodulation by prostaglandin D2 in canine airway smooth muscle

1987 ◽  
Vol 63 (4) ◽  
pp. 1396-1400 ◽  
Author(s):  
J. Tamaoki ◽  
K. Sekizawa ◽  
P. D. Graf ◽  
J. A. Nadel
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Prostaglandin D2 ◽  
Base Line ◽  
Field Stimulation ◽  
Electrical Field ◽  
Adrenergic Antagonist

To determine whether prostaglandin D2 (PGD2) modulates cholinergic neurotransmission in airway smooth muscle and, if so, what the mechanism of action is, we studied bronchial segments from dogs under isometric conditions in vitro. PGD2 (10(-8)-10(-5) M) elicited dose-dependent muscle contraction, which was reduced after blockade of muscarinic receptors, so that 50% effective dose (ED50) increased from 1.3 +/- 0.3 X 10(-6) to 3.9 +/- 1.0 X 10(-6) M by atropine (10(-6) M) (mean +/- SE, P less than 0.05). Physostigmine, at a concentration insufficient to alter base-line tension (10(-8) M), enhanced the PGD2-induced contraction and decreased ED50 to 6.4 +/- 0.5 X 10(-7) M (P less than 0.05). When added at the highest doses that did not cause spontaneous contraction (1.9 +/- 0.5 X 10(-7) M), PGD2 increased the contractile response to electrical field stimulation (1–50 Hz) by 21.9 +/- 6.6% (P less than 0.001). In contrast to this effect, the response to administered acetylcholine was not affected by PGD2. On the other hand, PGD2-induced augmentation of the response to electrical field stimulation (5 Hz) was further increased from 23.6 +/- 3.0 to 70.4 +/- 8.8% in the presence of physostigmine (10(-8) M) and was abolished by atropine but not affected by the alpha-adrenergic antagonist phentolamine or the histamine H1-blocker pyrilamine. These results suggest that the contraction of airway smooth muscle induced by PGD2 is in in part mediated by a cholinergic action and that PGD2 prejunctionally augments the parasympathetic contractile response, likely involving the accelerated release of acetylcholine at the neuromuscular junction.

scholarly journals Relaxation of guinea pig trachealis during electrical field stimulation increases with age

2002 ◽  
Vol 92 (5) ◽  
pp. 1835-1842 ◽  
Author(s):  
Pasquale Chitano ◽  
Carrie M. Cox ◽  
Thomas M. Murphy
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Time Course ◽  
Muscle Relaxation ◽  
Electrical Field Stimulation ◽  
Smooth Muscle Relaxation ◽  
Age Difference ◽  
Field Stimulation ◽  
Electrical Field

Our laboratory has previously shown that maturation of airway smooth muscle (ASM) contractility may play a role in the airway hyperresponsiveness displayed by juveniles of many species, including humans (Chitano P, Wang J, Cox CM, Stephens NL, and Murphy TM. J Appl Physiol 88: 1338–1345, 2000). ASM relaxation, which could also contribute to airway hyperresponsiveness, has neither been described nor quantified during maturation. Therefore, we studied ASM relaxation during and after electrical field stimulation (EFS) in tracheal strips from 1-wk-old, 3-wk-old, and 3-mo-old guinea pigs. Strips were stimulated (60 Hz, 18 V) at their optimal length for 15, 20, and 25 s, with and without the cyclooxygenase inhibitor indomethacin. To evaluate the role of the epithelium, deepithelialized strips from adult animals were also studied. New indexes were developed to quantify relaxation during EFS. We measured the time course of tension relaxation and its maximum rate (RTR) during the EFS, as well as the residual tension at the end of the EFS (TCTend). After EFS, we measured the maximum RTR and the time needed to reduce to half the TCTend. Relaxation during the EFS significantly increased with age. Indomethacin reduced this age difference by increasing relaxation in strips from younger animals. By contrast, removal of the epithelium in adult strips decreased relaxation. Relaxation after EFS decreased with age and was not affected by indomethacin. In adult strips, it was further reduced by epithelium removal. Our results show that during EFS 1) airway smooth muscle relaxation increases with age, 2) cyclooxygenase metabolites oppose relaxation in younger animals, and 3) epithelium removal inhibits relaxation. We suggest that a reduced ASM relaxing ability during stimulation may be involved in juvenile airway hyperresponsiveness.

Effects of mucosal removal on guinea-pig airway smooth muscle responsiveness

1986 ◽  
Vol 70 (6) ◽  
pp. 571-575 ◽  
Author(s):  
Christopher Murlas
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Airway Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Physiological Salt Solution ◽  
Induced Responses ◽  
Field Stimulation ◽  
Electrical Field ◽  
Airway Mucosa

1. The contractile response to histamine, acetylcholine (ACh), KCl or electrical field stimulation (EFS) was examined in paired tracheal rings (one of each being denuded by mucosal rubbing), which were mounted in muscle chambers filled with a continuously aerated physiological salt solution at 37°C. 2. Removal of the respiratory mucosa increased the sensitivity of airway muscle to ACh, histamine and EFS, but not to KCl. The hypersensitivity of denuded rings to histamine and EFS was greater than to ACh. Atropine reduced the histamine hypersensitivity observed. 3. Pretreating intact preparations with indomethacin augmented their responsiveness to EFS, histamine and ACh. 4. Indomethacin augmentation of histamine- and EFS-induced responses was greater in preparations without epithelium. 5. We conclude that the airway mucosa may be associated with a factor that reduces airway smooth muscle responsiveness to stimulation.

Nonadrenergic inhibitory nervous system in human airways

1976 ◽  
Vol 41 (5) ◽  
pp. 764-771 ◽  
Author(s):  
J. Richardson ◽  
J. Beland
Keyword(s):  
Smooth Muscle ◽  
Gastrointestinal Tract ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Inhibitory System ◽  
Electrical Field ◽  
Human Airways ◽  
Adrenergic Blocking ◽  
Stimulation Of

Human airways, from the middle of the trachea to the distal bronchi, were studied in vitro for the presence of inhibitory nerves. The tissue was obtained from operations and from recent autopsies. Electrical field stimulation of the tissues demonstrated cholinergic, excitatory nerves and their effect was blocked by atropine. Field stimulation of the tissues, in the presence of atropine, relaxed the smooth muscle even when the muscle was contracted by histamine. The field stimulation-induced relaxation was neither blocked nor modified by adrenergic blocking agents. Maximum relaxation of the bronchial muscle was obtained with a pulse duration of 1–2 ms, 70 V,and frequencies of 20 Hz and greater. The tracheal smooth muscle showed 85%of maximal relaxation with a frequency of 10 Hz. Tetrodotoxin, blocked the field stimulation-induced relaxation for pulse durations of 2 ms; this indicated that nerves were being stimulated. The airway system shows some of the characteristics of the nonadrenergic inhibitory system in the gastrointestinal tract and of the system reported in the guinea pig trachealis muscle.No evidence of adrenergic inhibitory fibers was found in the bronchial muscle with either pharmacological or histochemical techniques. These findings suggest that the nonadrenergic inhibitory system is the principal inhibitory system for the smooth muscle of human airways. We suggest that a defect in the airway system, such as that shown in the gastrointestinal tract, may be an explanation for the hyperreactive airways of asthma and chronic bronchitis.

In vivo loads on airway smooth muscle: the role of noncontractile airway structures

1992 ◽  
Vol 70 (4) ◽  
pp. 602-606 ◽  
Author(s):  
Philip Robinson ◽  
Mitsushi Okazawa ◽  
Tony Bai ◽  
Peter Paré
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Activation ◽  
Muscle Length ◽  
Tracheal Cartilage ◽  
Elastic Load ◽  
Muscle Shortening ◽  
Trachealis Muscle

The degree of airway smooth muscle contraction and shortening that occurs in vivo is modified by many factors, including those that influence the degree of muscle activation, the resting muscle length, and the loads against which the muscle contracts. Canine trachealis muscle will shorten up to 70% of starting length from optimal length in vitro but will only shorten by around 30% in vivo. This limitation of shortening may be a result of the muscle shortening against an elastic load such as could be applied by tracheal cartilage. Limitation of airway smooth muscle shortening in smaller airways may be the result of contraction against an elastic load, such as could be applied by lung parenchymal recoil. Measurement of the elastic loads applied by the tracheal cartilage to the trachealis muscle and by lung parenchymal recoil to smooth muscle of smaller airways were performed in canine preparations. In both experiments the calculated elastic loads applied by the cartilage and the parenchymal recoil explained in part the limitation of maximal active shortening and airway narrowing observed. We conclude that the elastic loads provided by surrounding structures are important in determining the degree of airway smooth muscle shortening and the resultant airway narrowing.Key words: elastic loads, tracheal cartilage, airway smooth muscle shortening.

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