Expression of airway contractile properties and acetylcholinesterase activity in swine

1989 ◽  
Vol 67 (1) ◽  
pp. 174-180 ◽  
Author(s):  
T. M. Murphy ◽  
R. W. Mitchell ◽  
J. S. Blake ◽  
M. M. Mack ◽  
E. A. Kelly ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Acetylcholinesterase Activity ◽  
Contractile Properties ◽  
Tracheal Smooth Muscle ◽  
Cholinesterase Inhibition ◽  
Maximal Response ◽  
Response Curves ◽  
Cross Sectional

We studied the effect of maturation on contractile properties of tracheal smooth muscle from seventeen 2-wk-old swine (2ws) and fifteen 10-wk-old swine (10ws) in situ and in vitro. The response to parasympathetic stimulation was studied in situ in isometrically fixed segments. Contraction was elicited at lower frequencies [half-maximal response to electrical stimulation (ES50) = 6.7 +/- 0.05 Hz] in 2ws than in 10ws (ES50 = 9.1 +/- 0.4 Hz; P less than 0.01). Despite substantial differences in morphometrically normalized cross-sectional area in 2ws (0.012 +/- 0.003 cm2) and 10ws (0.028 +/- 0.001 cm2; P less than 0.01), maximal active tension elicited by parasympathetic stimulation was similar (12.4 +/- 3.2 g/cm in 2ws vs. 13.3 +/- 2.3 g/cm in 10ws; P = NS). In separate in vitro studies in 25 tracheal smooth muscle strips from 10 swine, concentration-response curves generated with potassium-substituted Krebs solution (KCl) were similar in 2ws and 10ws. In 58 other strips (10 swine), maximal active force elicited with acetylcholine (ACh) in 2ws was significantly greater than for 10ws (P less than 0.001). Removal of the epithelium had no effect. However, cholinesterase inhibition with 10(-7) M physostigmine augmented the response to ACh in 10ws (P less than 0.02) but not 2ws. We demonstrate increased force generation and sensitivity to vagal stimulation in 2ws vs. 10ws, which corresponds to increased reactivity to ACh in vitro. The relative hyperresponsiveness in 2ws is specific for cholinergic response and is attenuated at least in part by maturation of the activity of acetylcholinesterase enzyme.

Maturation of acetylcholinesterase expression in tracheal smooth muscle contraction

1990 ◽  
Vol 259 (2) ◽  
pp. L130-L135 ◽  
Author(s):  
R. W. Mitchell ◽  
T. M. Murphy ◽  
E. Kelly ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Maximal Response ◽  
Response Curves ◽  
Electrical Field ◽  
Stimulus Response ◽  
Cholinergic Contraction

We examined postganglionic development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by cholinomimetic activation and electrical field depolarization in vitro. Epithelium-intact tracheal strips excised from 21 2-wk-old swine (2ws) and 19 10-wk-old swine (10ws) were tethered isometrically at optimal resting length, and responses were expressed as percent of the maximum to 63 mM potassium-chloride (%KCl). Cumulative concentration-response curves to KCl were equivalent for TSM from 2 and 10ws. However, maximal contraction to ACh in 2ws (168 +/- 8.4 %KCl) was greater than for 10ws (142 +/- 2.3 %KCl; P less than 0.02). Stimulus-response curves (field electrodes; AC source) demonstrated greater sensitivity for TSM in 10ws (stimulus causing 50% of the maximal response = 3.32 +/- 0.13 V in 2ws vs. 2.25 +/- 0.12 V in 10ws; P less than 0.001), indicating that the greater cholinomimetic responsiveness of 2ws did not result from augmented presynaptic nerve conduction. The AChase inhibitor, physostigmine, caused 1) greater sensitivity of responses elicited by electrical field stimulation in 2ws (P less than 0.05) but not in 10ws (P = NS), 2) augmentation of maximal responses to exogenous ACh in 10ws (27% increase; P less than 0.01) but not 2ws (2% increase; P = NS), and 3) a greater increase in sensitivity to cholinomimetic activation in 2ws compared with 10ws (P less than 0.02). These data demonstrate increased cholinergic contraction of TSM in 2 vs. 10ws that results at least in part from reduced AChase activity in the trachea of immature animals.

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.

Mechanisms of airway hypercontractility in basenji-greyhound dogs

1987 ◽  
Vol 63 (5) ◽  
pp. 2008-2014 ◽  
Author(s):  
T. M. Murphy ◽  
N. M. Munoz ◽  
C. A. Hirshman ◽  
J. S. Blake ◽  
A. R. Leff
Keyword(s):  
Maximal Response ◽  
Adrenergic Blockade ◽  
Vagus Nerves ◽  
Response Curves ◽  
Bronchial Smooth Muscle ◽  
Muscarinic Response ◽  
Contractile Forces ◽  
Stimulation Of

The comparative effects of contractile agonists and physiological stimulation of the tracheal and bronchial smooth muscle (BSM) response were studied isometrically in situ in five Basenji-greyhound (BG) and six mongrel dogs. Frequency-response curves generated by bilateral stimulation of the vagus nerves (0–20 Hz, 15–20 V, 2-ms duration) elicited greater maximal contraction in mongrel trachea (36.8 +/- 8.1 vs. 26.9 +/- 4.0 g/cm; P less than 0.02) and exhibited greater responsiveness in mongrel BSM (half-maximal response to electrical stimulation 3.0 +/- 1.1 vs. 7.0 +/- 0.5 Hz; P less than 0.05) compared with BG dogs. However, muscarinic sensitivity to intravenous methacholine (MCh) was substantially greater in BG dogs; MCh caused contraction greater than 1.5 g/cm at a mean dose of 3.0 X 10(-10) mol/kg for BG dogs compared with 5.1 X 10(-9) mol/kg for mongrel controls (P less than 0.03, Mann-Whitney rank-sum test). In contrast to the muscarinic response, the contractile response elicited by intravenous norepinephrine after beta-adrenergic blockade was similar in trachea and bronchus for both mongrel and BG dogs. Our data confirm previous in vitro demonstration of tracheal hyporesponsiveness in BG dogs and demonstrate that the contraction resulting from efferent parasympathetic stimulation is less in the BG than mongrel dogs. However, postsynaptic muscarinic responsiveness of BG BSM is substantially increased. We conclude that a component of airway responsiveness in BG dogs depends directly on contractile forces generated postsynaptically that are nongeometry dependent, postjunctional, and agonist specific.

Characterization of sulfidopeptide leukotriene responses in sheep tracheal smooth muscle in vitro

1991 ◽  
Vol 69 (6) ◽  
pp. 805-811 ◽  
Author(s):  
K. Tomioka ◽  
J. T. Jackowski ◽  
W. M. Abraham
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Tracheal Smooth Muscle ◽  
Response Curves ◽  
Leukotriene Antagonist ◽  
Dose Response Curves ◽  
The Right ◽  
Glutamyl Transpeptidase

We have investigated the effects of leukotrienes (LTs) on isolated tracheal smooth muscle from sheep sensitive to Ascaris suum antigen. LTC4 and LTD4 produced dose-dependent contractions of sheep trachea, but LTE4 was virtually inactive. YM-17690, a non-analogous LT agonist, produced no contractile response up to 100 μM. Indomethacin (5 μM) had no effect on LTC4- and LTD4-induced contractions. L-Serine borate (45 mM), an inhibitor of γ-glutamyl transpeptidase, shifted the dose–response curve of LTC4 to the left by 161-fold, and L-cysteine (6 mM), an inhibitor of aminopeptidase, shifted the dose–response curves of LTC4 and LTD4 to the left by 67- and 23-fold, respectively. YM-16638 (1 μM), an LT antagonist, shifted the dose–response curves of LTC4 and LTD4 to the right with pKB values of 6.57 and 7.13, respectively. YM-16638 did not affect LTC4-induced contractions of L-serine borate-treated tissues, indicating that the compound acts only on LTD4 receptors in sheep trachea. LTE4 (1 μM) shifted the dose–response curves of LTC4 and LTD4 to the right with pKB values of 6.87 and 7.31, respectively. YM-17690 (10 μM) showed effects similar to LTE4, suggesting that the compound acts as an LTE4 agonist in sheep trachea. These results suggest that in sheep tracheal smooth muscle (a) LTC4 and LTD4 produce contractions, (b) these LT-induced contractions are not mediated by cyclooxygenase products, (c) LTC4 is converted to LTD4 and then to LTE4, and (d) the potency of the LTC4- and LTD4-induced contractions is increased when their conversion to LTE4 is inhibited. This potentiation may result from the inability of LTE4 to contract sheep trachea and (or) its antagonist actions.Key words: leukotriene antagonist, receptors, asthma.

Exposure of immature rats to hyperoxia increases tracheal smooth muscle stress generation in vitro

1994 ◽  
Vol 76 (2) ◽  
pp. 743-749 ◽  
Author(s):  
M. B. Hershenson ◽  
M. E. Wylam ◽  
N. Punjabi ◽  
J. G. Umans ◽  
P. T. Schumacker ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Contractile Function ◽  
Stress Generation ◽  
Tracheal Smooth Muscle ◽  
Smooth Muscle Contractility ◽  
Cross Sectional ◽  
Induced Stress ◽  
Hyperoxic Exposure

Recently, we demonstrated that chronic exposure to hyperoxia causes in vivo airway muscarinic receptor hyperresponsiveness in the developing rat [Am. J. Physiol. 262 (Lung Cell. Mol. Physiol. 6): L263-L269, 1992]. To test whether airway cholinergic hyperresponsiveness might result from intrinsic alterations in smooth muscle contractility, we measured the effect of in vivo hyperoxia on the contractile force elicited by acetylcholine (ACh) of isometrically mounted tracheal rings in vitro. Tracheal rings were obtained from 3-wk-old rats exposed to air or to > 95% O2 for 8 days. Muscarinic responses were determined by measuring the force elicited by exposure to increasing concentrations of ACh. Responses were normalized to the morphometrically determined tracheal smooth muscle cross-sectional area in a plane perpendicular to the axis of force generation. In vivo O2 exposure significantly increased maximal ACh-induced stress generation (response to 10(-3) M ACh: air, 15.92 +/- 1.37 g/mm2; O2, 21.78 +/- 1.52 g/mm2; P = 0.010). The ACh-induced stress generation of cylinders from hyperoxic rats was substantially reduced by both epithelial removal and treatment with the cyclooxygenase inhibitor indomethacin. We conclude that in vivo hyperoxic exposure increases tracheal smooth muscle contractile function in vitro and that epithelium-derived prostaglandin(s) contributes to the observed increase in maximal contractile responsiveness.

scholarly journals Effects of Bradykinin on Pial Arteries and Arterioles in vitro and in situ

1983 ◽  
Vol 3 (2) ◽  
pp. 231-237 ◽  
Author(s):  
Michael Wahl ◽  
Alan R. Young ◽  
Lars Edvinsson ◽  
Franz Wagner
Keyword(s):  
Maximal Response ◽  
Guinea Pig Ileum ◽  
Response Curves ◽  
Pial Arteries ◽  
Cerebrovascular Resistance ◽  
Resistance Vessels ◽  
Prostaglandin F ◽  
The Stability

The effect of bradykinin on cerebrovascular resistance vessels was investigated by the use of in vitro and in situ preparations. Bradykinin, in the range of 10−10 to 10−5 M, elicited a concentration-dependent vasodilatation on both feline and human pial arteries in vitro; the half-maximal response was found to be approximately at 2.8 × 10−7 M and 1.3 × 10−8 M (EC50), respectively. This dilatatory effect of bradykinin in vitro was found only in arteries preconstricted with prostaglandin F2α or 5-hydroxytryptamine. In order to determine the effects of bradykinin on the diameter of cat pial arteries in situ, perivascular microapplication was employed. The dose-response curves obtained showed vasodilatation; the EC50 and the maximal response (EAm) were 4.4 × 10−7 M and 45.5% at 10−5 M, respectively. Statistically significant (p < 0.01) reactions were observed at 10−7 M and higher concentrations of bradykinin. The observed effects were independent of initial vessel size (80–260 μm). These in situ findings are very similar to those found in vitro. The isolated guinea pig ileum was used to check the stability of the bradykinin solutions. In this instance, a concentration-dependent contraction was found when “freshly prepared” or “5 hours stored” bradykinin was applied, indicating no measurable degradation of bradykinin. We conclude that bradykinin is a powerful vasodilator of both human and feline pial arteries.

scholarly journals Protective Effect of Nedocromil Against Insulin Induced Airway Hyper-Reactivity

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Mahjabeen Sharif ◽  
Bushra Tayyaba Khan ◽  
Ayesha Afzal ◽  
Fatima Qasim Malik ◽  
Mohammad Asim Anwar
Keyword(s):  
Smooth Muscle ◽  
Guinea Pigs ◽  
Acute Effect ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Protective Effects ◽  
Response Curves ◽  
Medical College ◽  
Inhaled Insulin

Background: Use of inhalable insulin is limited because it causes airway hyper-reactivity. So present study was designed to ameliorate inhalational insulin induced airway hyper-responsiveness.Objectives: The objective of the study was to evaluate the acute effects of insulin on airway reactivity and protective effects of nedocromil against insulin induced airway hyper-reactivity on isolated tracheal tissues of guinea pigs in vitro.Material and Methods: This experimental study was carried out in Pharmacology department of Army Medical College Rawalpindi from January 2012 to July 2012. We observed acute effect of insulin (10-7- 10-3 M) and insulin pretreated with nedocromil (10-5 M) on isolated tracheal strip of guinea pig (n=6) in vitro by constructing cumulative concentration response curves. The tracheal smooth muscle contractions were recorded with Transducer on Four Channel Oscillograph.Results: Insulin significantly increased the tracheal smooth muscle contraction. The mean ± SEM of maximum amplitudes of contraction with insulin and insulin pretreated with nedocromil were 35 ± 1.13 mm and 27.8 ± 1.27 mm respectively. So nedocromil significantly antagonized insulin elicited contractile effect. Conclusion: Nedocromil significantly inhibited the insulin mediated airway hyper-reactivity in guinea pigs. So we suggest that pretreatment of inhaled insulin with nedocromil may have clinical implication in amelioration of its potential respiratory adverse effects.

Halothane reduces myofilament Ca2+ sensitivity during muscarinic receptor stimulation of airway smooth muscle

1996 ◽  
Vol 271 (5) ◽  
pp. L719-L725 ◽  
Author(s):  
M. Akao ◽  
A. Hirasaki ◽  
K. A. Jones ◽  
G. Y. Wong ◽  
D. H. Bremerich ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Volatile Anesthetic ◽  
Second Messenger ◽  
Membrane Receptor ◽  
Tracheal Smooth Muscle ◽  
Maximal Response ◽  
Response Curves ◽  
Smooth Muscle Preparation ◽  
Kinase C ◽  
Second Messenger Systems

This study used a beta-escin-permeabilized canine tracheal smooth muscle preparation to test the hypothesis that the volatile anesthetic halothane decreases myofilament Ca2+ sensitivity by inhibiting the membrane receptor-linked second messenger systems that regulate myofilament Ca2+ sensitivity and not by inhibiting Ca(2+)-calmodulin activation of the contractile proteins. Acetylcholine (ACh) caused a GTP-dependent increase in force at constant submaximal cytosolic Ca2+ concentration. ACh, guanosine-5'-O-(3-thiotriphosphate), and the protein kinase C agonist 12,13-phorbol dibutyrate each significantly decreased the concentration of free Ca2+ producing a half-maximal response from 0.77 +/- 0.09 microM (Ca2+ alone) to 0.16 +/- 0.01, 0.19 +/- 0.02, and 0.37 +/- 0.03 microM, respectively, demonstrating an increase in myofilament Ca2+ sensitivity. Halothane (0.92 +/- 0.12 mM) had no effect on the free Ca2+ concentration-response curves generated by Ca2+ alone. However, in the presence of 3 microM ACh plus 10 microM GTP to maximally activate muscarinic receptors, halothane significantly increased the EC50 for free Ca2+ from 0.17 +/- 0.01 microM to 0.38 +/- 0.03 microM. These findings suggest that halothane decreases myofilament Ca2+ sensitivity in beta-escin-permeabilized canine tracheal smooth muscle by inhibiting the membrane receptor-linked second messenger systems that regulate myofilament Ca2+ sensitivity.

Interaction of contractile responses in canine tracheal smooth muscle

1987 ◽  
Vol 63 (2) ◽  
pp. 514-520 ◽  
Author(s):  
S. J. Gunst ◽  
J. Q. Stropp ◽  
N. A. Flavahan
Keyword(s):  
Smooth Muscle ◽  
Tracheal Smooth Muscle ◽  
Response Curves ◽  
Contractile Responses ◽  
Stimulus Response ◽  
Mediated Effects

Concentration-response curves for norepinephrine, acetylcholine, and 5-hydroxytryptamine were obtained in vitro alone and after precontraction with histamine, 5-hydroxytryptamine, or acetylcholine. Responses obtained to each agonist after precontraction were greater than responses to the agonist alone after subtraction of the force due to the precontracting stimulus. Augmentation of responses after precontraction was the greatest for norepinephrine, less for 5-hydroxytryptamine, and least for acetylcholine. Verapamil had no significant effect on the augmentation of responses to either 5-hydroxytryptamine or acetylcholine caused by precontraction. When the efficacy of acetylcholine was decreased by receptor alkylation with phenoxybenzamine, the augmentation of responses to acetylcholine caused by precontraction with histamine was significantly enhanced. Differences in the magnitude of the effect of precontraction on responses to different agonists may reflect differences in their efficiency of stimulus-response coupling in canine tracheal smooth muscle, or they may result from an increased expression of distinct receptors or receptor-mediated effects uncovered by the facilitory stimuli.

Functional characteristics of canine costal and crural diaphragm

1988 ◽  
Vol 65 (5) ◽  
pp. 2253-2260 ◽  
Author(s):  
G. A. Farkas ◽  
D. F. Rochester
Keyword(s):  
Contractile Properties ◽  
Force Frequency ◽  
Cross Sectional ◽  
Volume Functional ◽  
Generating Capacity ◽  
Residual Capacity ◽  
Crural Diaphragm ◽  
Muscle Cross Sectional Area

We estimated the in situ force-generating capacity of the costal and crural portions of the canine diaphragm by relating in vitro contractile properties and diaphragmatic dimensions to in situ lengths. Piezoelectric crystals were implanted on right costal and left crural diaphragms of anesthetized dogs, via midline laparatomy. With the abdomen reclosed, diaphragm lengths were recorded at five lung volumes. Contractile properties of excised muscle bundles were then measured. In vitro force-frequency and length-tension characteristics of the costal and crural diaphragms were virtually identical; their optimal force values were 2.15 and 2.22 kg/cm2, respectively. In situ, at residual volume, functional residual capacity (FRC), and total lung capacity the costal diaphragm lay at 102, 95, and 60% of optimal length (Lo), whereas the crural diaphragm lay at 88, 84, and 66% of Lo. Muscle cross-sectional area was 40% greater in costal than in crural diaphragms. Considering in situ lengths, cross-sectional areas, and in vitro length-tension characteristics at FRC, the costal diaphragm could exert 60% more force than the crural diaphragm.

Sign in / Sign up

Export Citation Format

Share Document