Activation of alpha-adrenergic response in tracheal smooth muscle: a postreceptor mechanism

1983 ◽  
Vol 54 (6) ◽  
pp. 1469-1476 ◽  
Author(s):  
P. J. Barnes ◽  
B. E. Skoogh ◽  
J. K. Brown ◽  
J. A. Nadel
Keyword(s):  
Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Tracheal Smooth Muscle ◽  
Adrenergic Blockade ◽  
Adrenergic Response ◽  
Receptor Number ◽  
Related Process

We have investigated the activation of alpha-adrenergic contractile responses in dog tracheal smooth muscle. After cholinergic and beta-adrenergic blockade, neither electrical field stimulation nor alpha-adrenergic agonists caused contraction of trachealis strips in vitro, but after exposure to histamine or serotonin a striking contractile response was obtained. Similar activation of the contractile response to norepinephrine was seen in isolated tracheal segments in vivo after exposure to histamine and serotonin. This response was mediated predominantly by alpha 2-adrenoceptors, because the alpha 2-antagonist yohimbine was a potent inhibitor whereas the alpha 1-antagonist prazosin was a weak inhibitor of the response to both electrical stimulation and exogenous agonists. Using [3H]yohimbine to label alpha 2-receptors and [3H]prazosin to label alpha 1-receptors, we confirmed the preponderance of alpha 2-receptors in trachealis membranes but found no increase in either receptor number or affinity after incubating muscle strips with histamine. The magnitude of alpha-adrenergic contraction was significantly related to the magnitude of precontraction by histamine and serotonin both in vitro and in vivo but persisted after washout. Acetylcholine was much less potent in activating the alpha-adrenergic response. We conclude that activation of airway alpha-adrenergic responses involves a postreceptor mechanism not directly related to membrane depolarization, but involving some related process such as activation of calcium channels.

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.

Effect of in vitro preconditioning on tracheal smooth muscle responsiveness

1991 ◽  
Vol 260 (2) ◽  
pp. L168-L173 ◽  
Author(s):  
R. W. Mitchell ◽  
E. Kelly ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Contractile Response ◽  
Electrical Field Stimulation ◽  
Tissue Perfusion ◽  
Tracheal Smooth Muscle ◽  
Equilibration Time ◽  
Active Tension ◽  
Perfusion Chamber ◽  
Anesthetized Dogs

We evaluated the effect of preconditioning of the isometric contractile response of canine tracheal smooth muscle (TSM) in vitro. Strips of epithelium-free TSM (n = 90) were excised from 16 anesthetized dogs and fixed isometrically in tissue perfusion chambers. Experiments were performed using methods previously reported in which the following parameters were investigated: 1) quiescent equilibration time in the perfusion chamber (0-120 min); 2) effect of repeated exchange of perfusate; 3) method of determining the optimal resting length (Lmax) for presetting of resting tension (RT); 4) effect of precontraction during the equilibration phase on the contractile response to agonists administered subsequently; and 5) method of determining RT on the response to muscarinic stimulation. When other variables were uniform, neither equilibration time nor perfusate exchange affected potency or efficacy of the response generated subsequently to acetylcholine (ACh). However, both potency (range of EC50: -5.71 +/- 0.14 log M to -6.52 +/- 0.24 log M; P less than 0.02) and efficacy (range of maximal active tension: 1,143 +/- 268 g/cm2 to 2,878 +/- 151 g/cm2; P less than 0.001) of ACh were altered substantially as a result of the method used to estimate Lmax. Repeated precontraction by electrical field stimulation or with 127 mM KCl did not alter potency or efficacy of contraction elicited by ACh. Maximal active tension generated with 10(3) M ACh was 2,878 +/- 151 g/cm2 after 12–15 tetanizing field stimulations and 2,696 +/- 198 g/cm2 after 5–7 contractions with 127 mM KCl (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Efficacy of fexofenadine in isolated rat tracheas

2013 ◽  
Vol 51 (4) ◽  
pp. 376-380
Author(s):  
W.S. Lai ◽  
Y.Y. Lin ◽  
Y.H. Chu ◽  
C.H. Wang ◽  
H.W. Wang
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Histamine Receptor ◽  
Tracheal Smooth Muscle ◽  
Dependent Manner ◽  
Chemical Mediator ◽  
Bronchial Inflammation ◽  
Isolated Rat

Objectives: Histamine is an important chemical mediator in both nasal and bronchial inflammation in patients with allergic rhinitis and asthma. The effect of histamine receptor-1 antagonists on nasal mucosa in vivo is well known, however, the effect on tracheal smooth muscle has rarely been explored. The purpose of this study was to determine the effects of fexofenadine on isolated tracheal smooth muscle in vitro. Methods: Six tracheal strips were used for each experiment, and one untreated strip served as a control. We examined the effectiveness of fexofenadine on isolated rat tracheal smooth muscle by testing the effect on: 1) tracheal smooth muscle resting tension; 2) contraction caused by 10E-6 M methacholine as a parasympathetic mimetic; and 3) electrically induced tracheal smooth muscle contractions. Results: The results indicated that addition of methacholine caused the trachea to contract in a dose-dependent manner. The addition of fexofenadine at a dose of 10E-4 M elicited a significant relaxation response compared to 10E-6 M methacholine-induced contraction. There were no detectable changes in the peak tension of electrical field stimulation-induced contractions in the fexofenadine group. Conclusion: High concentrations of fexofenadine had an anti-cholinergic effect. In addition to diminishing histamine-mediated allergic symptoms, fexofenadine may have a potentially therapeutic implication in alleviating asthma-related symptoms due to reducing methacholine-induced contractions of tracheal smooth muscle though these aspects were not studied.

Mechanical properties of human bronchial smooth muscle in vitro

1992 ◽  
Vol 73 (4) ◽  
pp. 1481-1485 ◽  
Author(s):  
K. Ishida ◽  
P. D. Pare ◽  
J. Hards ◽  
R. R. Schellenberg
Keyword(s):  
Mechanical Properties ◽  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Tracheal Smooth Muscle ◽  
Cross Sectional ◽  
Velocity Of Shortening ◽  
Muscle Shortening ◽  
Tension Generation ◽  
Very High

The in vitro mechanical properties of smooth muscle strips from 10 human main stem bronchi obtained immediately after pneumonectomy were evaluated. Maximal active isometric and isotonic responses were obtained at varying lengths by use of electrical field stimulation (EFS). At the length (Lmax) producing maximal force (Pmax), resting tension was very high (60.0 +/- 8.8% Pmax). Maximal fractional muscle shortening was 25.0 +/- 9.0% at a length of 75% Lmax, whereas less shortening occurred at Lmax (12.2 +/- 2.7%). The addition of increasing elastic loads produced an exponential decrease in the shortening and velocity of shortening but increased tension generation of muscle strips stimulated by EFS. Morphometric analysis revealed that muscle accounted for 8.7 +/- 1.5% of the total cross-sectional tissue area. Evaluation of two human tracheal smooth muscle preparations revealed mechanics similar to the bronchial preparations. Passive tension at Lmax was 10-fold greater and maximal active shortening was threefold less than that previously demonstrated for porcine trachealis by us of the same apparatus. We attribute the limited shortening of human bronchial and tracheal smooth muscle to the larger load presumably provided by a connective tissue parallel elastic component within the evaluated tissues, which must be overcome for shortening to occur. We suggest that a decrease in airway wall elastance could increase smooth muscle shortening, leading to excessive responses to contractile agonists, as seen in airway hyperresponsiveness.

Phosphorylation of caldesmon by ERK MAP kinases in smooth muscle

2000 ◽  
Vol 278 (4) ◽  
pp. C718-C726 ◽  
Author(s):  
Jason C. Hedges ◽  
Brian C. Oxhorn ◽  
Michael Carty ◽  
Leonard P. Adam ◽  
Ilia A. Yamboliev ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Map Kinase ◽  
Map Kinases ◽  
Isometric Force ◽  
Phosphorylation Site ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Muscarinic Agonists

Phosphorylation of h-caldesmon has been proposed to regulate airway smooth muscle contraction. Both extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinases phosphorylate h-caldesmon in vitro. To determine whether both enzymes phosphorylate caldesmon in vivo, phosphorylation-site-selective antibodies were used to assay phosphorylation of MAP kinase consensus sites. Stimulation of cultured tracheal smooth muscle cells with ACh or platelet-derived growth factor increased caldesmon phosphorylation at Ser789 by about twofold. Inhibiting ERK MAP kinase activation with 50 μM PD-98059 blocked agonist-induced caldesmon phosphorylation completely. Inhibiting p38 MAP kinases with 25 μM SB-203580 had no effect on ACh-induced caldesmon phosphorylation. Carbachol stimulation increased caldesmon phosphorylation at Ser789 in intact tracheal smooth muscle, which was blocked by the M2 antagonist AF-DX 116 (1 μM). AF-DX 116 inhibited carbachol-induced isometric contraction by 15 ± 1.4%, thus dissociating caldesmon phosphorylation from contraction. Activation of M2 receptors leads to activation of ERK MAP kinases and phosphorylation of caldesmon with little or no functional effect on isometric force. P38 MAP kinases are also activated by muscarinic agonists, but they do not phosphorylate caldesmon in vivo.

scholarly journals Mice that overexpress Cu/Zn superoxide dismutase are resistant to allergen-induced changes in airway control

2000 ◽  
Vol 279 (2) ◽  
pp. L350-L359 ◽  
Author(s):  
Gary L. Larsen ◽  
Carl W. White ◽  
Katsuyuki Takeda ◽  
Joan E. Loader ◽  
Dee Dee H. Nguyen ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Smooth Muscle ◽  
Transgenic Mice ◽  
Neural Control ◽  
Electrical Field Stimulation ◽  
Tracheal Smooth Muscle ◽  
Wild Type ◽  
Airway Control ◽  
Induced Changes

Within the respiratory epithelium of asthmatic patients, copper/zinc-containing superoxide dismutase (Cu/Zn SOD) is decreased. To address the hypothesis that lung Cu/Zn SOD protects against allergen-induced injury, wild-type and transgenic mice that overexpress human Cu/Zn SOD were either passively sensitized to ovalbumin (OVA) or actively sensitized by repeated airway exposure to OVA. Controls included nonsensitized wild-type and transgenic mice given intravenous saline or airway exposure to saline. After aerosol challenge to saline or OVA, segments of tracheal smooth muscle were obtained for in vitro analysis of neural control. In response to electrical field stimulation, wild-type sensitized mice challenged with OVA had significant increases in cholinergic reactivity. Conversely, sensitized transgenic mice challenged with OVA were resistant to changes in neural control. Stimulation of tracheal smooth muscle to elicit acetylcholine release showed that passively sensitized wild-type but not transgenic mice released more acetylcholine after OVA challenge. Function of the M2 muscarinic autoreceptor was preserved in transgenic mice. These results demonstrate that murine airways with elevated Cu/Zn SOD were resistant to allergen-induced changes in neural control.

Effect of airway inflammation on smooth muscle shortening and contractility in guinea pig trachealis

1993 ◽  
Vol 265 (6) ◽  
pp. L549-L554 ◽  
Author(s):  
R. W. Mitchell ◽  
I. M. Ndukwu ◽  
K. Arbetter ◽  
J. Solway ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Neurogenic Inflammation ◽  
Isometric Force ◽  
Electrical Field Stimulation ◽  
Shortening Velocity ◽  
Lever System ◽  
Force Velocity

We studied the effect of either 1) immunogenic inflammation caused by aerosolized ovalbumin or 2) neurogenic inflammation caused by aerosolized capsaicin in vivo on guinea pig tracheal smooth muscle (TSM) contractility in vitro. Force-velocity relationships were determined for nine epithelium-intact TSM strips from ovalbumin-sensitized (OAS) vs. seven sham-sensitized controls and TSM strips for seven animals treated with capsaicin aerosol (Cap-Aer) vs. eight sham controls. Muscle strips were tethered to an electromagnetic lever system, which allowed isotonic shortening when load clamps [from 0 to maximal isometric force (Po)] were applied at specific times after onset of contraction. Contractions were elicited by supramaximal electrical field stimulation (60 Hz, 10-s duration, 18 V). Optimal length for each muscle was determined during equilibration. Maximal shortening velocity (Vmax) was increased in TSM from OAS (1.72 +/- 0.46 mm/s) compared with sham-sensitized animals (0.90 +/- 0.15 mm/s, P < 0.05); Vmax for TSM from Cap-Aer (0.88 +/- 0.11 mm/s) was not different from control TSM (1.13 +/- 0.08 mm/s, P = NS). Similarly, maximal shortening (delta max) was augmented in TSM from OAS (1.01 +/- 0.15 mm) compared with sham-sensitized animals (0.72 +/- 0.14 mm, P < 0.05); delta max for TSM from Cap-Aer animals (0.65 +/- 0.11 mm) was not different from saline aerosol controls (0.71 +/- 0.15 mm, P = NS). We demonstrate Vmax and delta max are augmented in TSM after ovalbumin sensitization; in contrast, neurogenic inflammation caused by capsaicin has no effect on isolated TSM contractility in vitro. These data suggest that airway hyperresponsiveness in vivo that occurs in association with immunogenic or neurogenic inflammation may result from different effects of these types of inflammation on airway smooth muscle.

Relationship between in vivo Airway Reactivity and in vitro Responsiveness of Tracheal Smooth Muscle in Inbred Rats

Respiration ◽  
1988 ◽  
Vol 54 (1) ◽  
pp. 108-113 ◽  
Author(s):  
G.U. Di Maria ◽  
J.G. Martin ◽  
S. Bellofiore ◽  
A. Mistretta
Keyword(s):  
Smooth Muscle ◽  
Tracheal Smooth Muscle ◽  
Airway Reactivity ◽  
Inbred Rats

Structural and functional study of control of canine tracheal smooth muscle

1980 ◽  
Vol 238 (1) ◽  
pp. C27-C33 ◽  
Author(s):  
M. S. Kannan ◽  
E. E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Sympathetic Nerves ◽  
Tracheal Smooth Muscle ◽  
Functional Study ◽  
Field Stimulation ◽  
Electron Microscopic ◽  
Microscopic Studies ◽  
Stimulation Of

The structural bases for myogenic and neurogenic control of canine tracheal smooth muscle were studied. At optimum lengths, strips of muscle showed insignificant neurogenic or myogenic tone. Atropine and/or tetrodotoxin blocked the contractile responses elicited on electrical field stimulation of intrinsic nerves. After raising the tone with tetraethylammonium ion and in the presence of atropine, field stimulation of nerves caused a relaxation, a major component of which was blocked by propranolol and/or tetrodotoxin, suggesting an effect mediated through interaction of mediator released from sympathetic nerves with beta-adrenergic receptors. Electron microscopic studies revealed gap junctions between extensions of smooth-muscle cells and a sparse innervation. The axonal varicosities, corresponding to cholinergic (predominantly) and adrenergic (occasionally) nerves, were seen predominantly in the clefts between cell bundles. The physiological responses were compared with the morphological features. Although this muscle exhibits multiunit behavior in vitro, implying that nerves initiate the coordinate activity, its ultrastructural features suggest a potential for single-unit behavior.

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.

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