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.

Ontogeny of shortening velocity in porcine trachealis

1992 ◽  
Vol 262 (3) ◽  
pp. L280-L285 ◽  
Author(s):  
K. Ikeda ◽  
R. W. Mitchell ◽  
K. A. Guest ◽  
C. Y. Seow ◽  
C. F. Kirchhoff ◽  
...  
Keyword(s):  
Isometric Force ◽  
Electrical Field Stimulation ◽  
Contractile Force ◽  
Postnatal Life ◽  
Maximal Velocity ◽  
Shortening Velocity ◽  
Lever System ◽  
Velocity Of Shortening ◽  
Force Velocity ◽  
The Relationship

We examined the effect of maturation on force-velocity (F-V) parameters in porcine tracheal smooth muscle (TSM) to determine the relationship between maximal isometric contractile force (Po) and maximal velocity of shortening (Vmax). Strips of TSM excised from 1-day-old neonatal swine (neo; n = 8), 2-wk-old swine (2ws; n = 7), and 10-wk-old swine (10ws; n = 7) were tethered to an electromagnetic lever system for F-V analysis of contractility. TSM strips were activated by electrical field stimulation at optimal resting tension, voltage, and length (Lo) so that maximal reproducible contractile force (Po) was elicited. Velocities were measured at the early phase of isometric contraction (3.1 +/- 0.1 s for neo, 2.9 +/- 0.1 s for 2ws, and 3.1 +/- 0.1 s for 10ws; P = NS). Shortening velocity increased progressively with maturation; Vmax was 0.164 +/- 0.011 Lo/s for neo, 0.194 +/- 0.013 Lo/s for 2ws (P less than 0.05 vs. neo), and 0.260 +/- 0.024 Lo/s for 10ws (P less than 0.01 vs. neo; P less than 0.05 vs. 2ws). Maximal isometric force generation increased substantially during the first 2 wk of postnatal life and thereafter returned to neonatal levels; Po was 71.5 +/- 2.1 mN/mm2 for neo, 95.4 +/- 7.0 mN/mm2 for 2ws, and 74.7 +/- 6.2 mN/mm2 for 10ws (P less than 0.05, 2ws vs. neo and 10ws). In separate studies, we also determined whether differences in Vmax occurred during the normal cycling phase of the cross bridge (3 s) or during the slowly cycling phase of the latch bridge (8 s) in tissue from 12 additional animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Passive sensitization of human bronchi augments smooth muscle shortening velocity and capacity

1994 ◽  
Vol 267 (2) ◽  
pp. L218-L222 ◽  
Author(s):  
R. W. Mitchell ◽  
E. Ruhlmann ◽  
H. Magnussen ◽  
A. R. Leff ◽  
K. F. Rabe
Keyword(s):  
Smooth Muscle ◽  
Human Serum ◽  
Immunoglobulin E ◽  
Isometric Force ◽  
Lung Resection ◽  
Electrical Field Stimulation ◽  
Shortening Velocity ◽  
Passive Sensitization ◽  
High Concentrations

We assessed whether incubation with human serum from atopic individuals containing high concentrations of immunoglobulin E (IgE) causes augmentation of maximal contraction of human bronchial smooth muscle from non-atopic subjects in vitro. Bronchi were obtained from eight patients undergoing lung resection, and force-velocity relationships were determined for eight pairs of epithelium-intact bronchial rings of generations 6-7 using an electromagnetic lever system, which allowed isotonic shortening when load-clamps [from 0 to maximal isometric force (P0)] were applied at specific times after onset of contraction. Contractions were elicited by supramaximal electrical field stimulation (50 Hz, 10 s train duration, 25 V). Optimal length (Lo) for each tissue was determined during equilibration. After resection, tissues were sensitized passively with human sera containing high titers (> 1,000 U/ml) of IgE by incubation for 16 h at 20 degrees C. Maximal shortening velocity (Vmax) was increased for passively sensitized bronchi [0.1150 +/- 0.0240 1/2 circumferences/s (1/2Cir/s)] compared with sham-sensitized bronchi [0.0731 +/- 0.0152 1/2Cir/s, P = 0.038]. Similarly, maximal shortening (delta Lmax) was augmented in sensitized bronchial rings (11.27 +/- 1.80 %Lo) compared with sham-sensitized tissues (8.19 +/- 1.39 %Lo, P = 0.012). However, P0 did not differ between sensitized (122.5 +/- 24.4 mN/cm2) compared with sham-sensitized tissues (138.4 +/- 32.1 mN/cm2, P = 0.642). Our data are the first demonstration that Vmax and delta Lmax are augmented in sensitized but not challenged human bronchial rings after passive sensitization using human serum containing high concentrations of IgE.

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.

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.

Effects of microtubule disruption on force, velocity, stiffness and [Ca2+]i in porcine coronary arteries

2000 ◽  
Vol 279 (5) ◽  
pp. H2493-H2501 ◽  
Author(s):  
Richard J. Paul ◽  
Peggy Sue Bowman ◽  
Michael S. Kolodney
Keyword(s):  
Smooth Muscle ◽  
Coronary Arteries ◽  
Isometric Force ◽  
Shortening Velocity ◽  
Cultured Fibroblasts ◽  
Microtubule Disruption ◽  
Highly Sensitive ◽  
Artery Stiffness ◽  
Force Velocity ◽  
Microtubule Stabilizer

Force generated by smooth muscle cells is believed to result from the interaction of actin and myosin filaments and is regulated through phosphorylation of the myosin regulatory light chain (LC20). The role of other cytoskeleton filaments, such as microtubules and intermediate filaments, in determining the mechanical output of smooth muscle is unclear. In cultured fibroblasts, microtubule disruption results in large increases in force similar to contractions associated with LC20 phosphorylation (15). One hypothesis, the “tensegrity” or “push-pull” model, attributes this increase in force to the disruption of microtubules functioning as rigid struts to resist force generated by actin-myosin interaction (9). In porcine coronary arteries, the disruption of microtubules by nocodazole (11 μM) also elicited moderate but significant increases in isometric force (10–40% of a KCl contracture), which could be blocked or reversed by taxol (a microtubule stabilizer). We tested whether this nocodazole-induced force was accompanied by changes in coronary artery stiffness or unloaded shortening velocity, parameters likely to be highly sensitive to microtubule resistance elements. Few changes were seen, ruling out push-pull mechanisms for the increase in force by nocodazole. In contrast, the intracellular calcium concentration, measured by fura 2 in the intact artery, was increased by nocodazole in parallel with force, and this was inhibited and/or reversed by taxol. Our results indicate that microtubules do not significantly contribute to vascular smooth muscle mechanical characteristics but, importantly, may play a role in modulation of Ca2+ signal transduction.

Effect of Propofol on Norepinephrine-induced Increases in [Ca2+](i) and Force in Smooth Muscle of the Rabbit Mesenteric Resistance Artery 

1998 ◽  
Vol 88 (6) ◽  
pp. 1566-1578 ◽  
Author(s):  
Nami Imura ◽  
Yoshihisa Shiraishi ◽  
Hirotada Katsuya ◽  
Takeo Itoh
Keyword(s):  
Smooth Muscle ◽  
Isometric Force ◽  
Resistance Artery ◽  
Resistance Arteries ◽  
High K ◽  
Small Resistance ◽  
Vasodilating Activity ◽  
Mesenteric Resistance Artery

Background Propofol (2,6-diisopropylphenol) possesses vasodilating activity in vivo and in vitro. The propofol-induced relaxation of agonist-induced contractions in small resistance arteries has not been clarified. Methods The effect of propofol was examined on the contractions induced by norepinephrine and high K+ in endothelium-denuded rabbit mesenteric resistance artery in vitro. The effects of propofol on the [Ca2+]i mobilization induced by norepinephrine and high K+ were studied by simultaneous measurement of [Ca2+]i using Fura 2 and isometric force in ryanodine-treated strips. Results Propofol attenuated the contractions induced by high K+ and norepinephrine, the effect being greater on the high K+-induced contraction than on the norepinephrine-induced contraction. In Ca2+-free solution, norepinephrine produced a transient contraction resulting from the release of Ca2+ from storage sites that propofol attenuated. In ryanodine-treated strips, propofol increased the resting [Ca2+]i but attenuated the increases in [Ca2+]i and force induced by both high K+ and norepinephrine. In the presence of nicardipine, propofol had no inhibitory action on the residual norepinephrine-induced [Ca2+]i increase, whereas it still modestly increased resting [Ca2+]i, as in the absence of nicardipine. Conclusions In smooth muscle of the rabbit mesenteric resistance artery, propofol attenuates norepinephrine-induced contractions due to an inhibition both of Ca2+ release and of Ca2+ influx through L-type Ca2+ channels. Propofol also increased resting [Ca2+]i, possibly as a result of an inhibition of [Ca2+]i removal mechanisms. These results may explain in part the variety of actions seen with propofol in various types of vascular smooth muscle.

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.

Differential tachykinin receptor subtype activation in capsaicin and KCl contractions of guinea pig trachealis

1995 ◽  
Vol 269 (6) ◽  
pp. L837-L842
Author(s):  
R. W. Mitchell ◽  
I. M. Ndukwu ◽  
A. Herrnreiter ◽  
K. Uzendoski ◽  
B. Gitter ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Electrical Field Stimulation ◽  
Receptor Subtype ◽  
Nk1 Receptor ◽  
Electrical Field ◽  
Tachykinin Receptor ◽  
Nk1 Receptor Antagonist

We assessed the role of endogenously secreted tachykinins in mediating contraction caused by potassium chloride (KCl) in guinea pig tracheal smooth muscle (TSM) strips in vitro. Maximal isometric contraction was elicited with approximately 45 mM KCl and was 196 +/- 8% of the response to electrical field stimulation (% EFS) in the same tissues. Muscarinic receptor blockade with atropine modestly attenuated this contraction caused by KCl to 175 +/- 9 %EFS (P < 0.05), and treatment with a selective neurokinin subtype 1 (NK1) receptor antagonist, LY-297911, caused even greater inhibition of KCl-elicited contraction to 124 +/- 8 %EFS (P < 0.001). By contrast, SR-48968, a selective NK2 antagonist, had no effect on contraction caused by KCl (183 +/- 9 %EFS; P = NS vs. KCl alone). However, given together at the same concentration, SR-48968 augmented the inhibition of contraction caused by LY-297911 to 93 +/- 15 %EFS (P < 0.05 vs. LY-297911 alone). In contrast to the effect on KCl-induced contraction, LY-297911 caused only moderate inhibition of the contraction caused by capsaicin to 81 +/- 13 %EFS (P < 0.05 vs. control, 114 +/- 15 %EFS), whereas SR-48968 caused substantial attenuation of contraction caused by capsaicin to 23 +/- 5 %EFS (P < 0.005 vs. LY-297911). We demonstrate that a significant portion of the contraction caused by KCl, in addition to capsaicin, is elicited in guinea pig TSM through neurokinin secretion. However, NK1 receptors predominantly mediate contraction caused by KCl, and NK2 receptors predominantly mediate contraction elicited by capsaicin in guinea pig airway smooth muscle.

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.

The Bronchodilator Activity of AY-22093, a Prostanoic Acid Derivative

1974 ◽  
Vol 52 (1) ◽  
pp. 1-7 ◽  
Author(s):  
R. Greenberg ◽  
G. Beaulieu
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Guinea Pig ◽  
Acid Derivative ◽  
Prostaglandin E ◽  
Significant Protection ◽  
In Vitro Techniques ◽  
Bronchodilator Activity

The bronchodilator activities of AY-22093, prostaglandin E2 (PGE2), and isoproterenol were compared using in vivo and in vitro techniques. In the conscious guinea pig, an aerosol of AY-22093, PGE2, and isoproterenol afforded significant protection against histamine-induced bronchospasm; AY-22093 and isoproterenol were equally effective in protecting against antigen-induced anaphylaxis. In the anesthetized guinea pig, using the Konzett and Rössler technique, PGE2 (1 μg/kg, intravenously (i.v.)) inhibited the bronchoconstriction induced by histamine (10 μg/kg, i.v.) by 63% as compared with 37% inhibition after AY-22093 (1 μg/kg, i.v.). Larger intravenous doses of PGE2 and AY-22093 (10 and 20 μg/kg) caused almost complete inhibition of the histamine-induced bronchoconstriction. The administration of PGE2 (0.5–10 μg) or AY-22093 (5–100 μg) by aerosol inhibited the bronchoconstriction induced by histamine (10 μg/kg, i.v.) by 20–70%. Maximum bronchodilator effects occurred within 3 min and lasted for as long as 30 min after either route of administration. Both compounds caused a fall in blood pressure after intravenous but not after aerosol administration. AY-22093 relaxed the guinea pig tracheal strip where tone was induced by carbachol. This relaxation was not altered by propranolol. The results indicate that AY-22093 is a bronchodilator qualitatively similar to PGE2, having a direct effect on smooth muscle but less potent than PGE2.

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