Physiological and pharmacological response of canine bronchial smooth muscle in situ

1983 ◽  
Vol 54 (1) ◽  
pp. 215-224 ◽  
Author(s):  
S. G. Hendrix ◽  
N. M. Munoz ◽  
A. R. Leff

We studied the isometric response of bronchial smooth muscle in a single third-order bronchus of 24 dogs in situ. Length-tension studies were performed in six dogs by repeated injection of 10(-5) mol acetylcholine (ACh) into the right bronchoesophageal artery, and the resting tension (30.6 +/- 6.9 g/cm) and length (0.76 +/- 0.14 cm) permitting maximal contraction were determined. In eight other dogs, dose-related bronchial contraction was obtained with 10(-10) to 10(-5) mol intra-arterial (ia) ACh. Supramaximal electrical stimulation of the right cervical vagus nerve and bronchial parasympathetic ganglion stimulation with ia 1–1-dimethyl-4-phenylpiperazinium (DMPP) also caused bronchial contraction. The maximal response to ia ACh (28.5 +/- 1.7 g/cm), supramaximal electrical stimulation (15.2 +/- 1.1 g/cm), and ia DMPP (10.5 +/- 3.0 g/cm) was blocked by an ia dose of atropine (1–5 micrograms/kg) that did not alter the sympathetic relaxation response in the trachea. In four dogs, the bronchial response to sympathetic activation was studied by intravenous (iv) bolus injection of DMPP after cholinergic blockade with atropine. DMPP (25 micrograms/kg iv) caused 9.5 +/- 2.2 g/cm bronchial relaxation, which was blocked completely by 2–4 mg/kg iv propranolol. In six other dogs, hypoxia induced by ventilation with pure nitrogen caused bronchial contraction, which was blocked by vagotomy, atropine, and hexamethonium. We report a sensitive method for selective measurement of bronchial smooth muscle response in a single resistance bronchus. This preparation preserves regional innervation and circulation and permits selective physiological stimulation in situ.

1983 ◽  
Vol 55 (6) ◽  
pp. 1803-1810 ◽  
Author(s):  
E. R. Garrity ◽  
N. P. Stimler ◽  
N. M. Munoz ◽  
R. Fried ◽  
A. R. Leff

We studied the response of bronchial smooth muscle to mast cell degranulation with Ascaris suum antigen (AA) and compound 48/80 (48/80) in 26 mongrel dogs in situ. Bronchial smooth muscle response was measured isometrically in situ from a segment of the right middle lobe bronchus; tracheal response was monitored isometrically as a control. After intra-arterial (ia) injection of AA into the bronchial circulation, bronchial contraction preceded tracheal contraction by 19.2 +/- 4.6 s (P less than 0.002). Bronchial contraction to AA (21.7 +/- 3.4 g) was substantially greater than to 48/80 (10.5 +/- 1.8 g, P less than 0.05) corresponding to differences in maximal systemic histamine concentrations (146 +/- 24.1 vs. 1000 +/- 236 ng/ml, P less than 0.01). In 5 dogs, the effect of leukotriene D4 (LTD4) and FPL 55712 was studied. Injection of 10(-8) mol ia LTD4 caused no bronchial contraction. In four dogs, 10(-7) mol FPL 55712 caused no bronchial relaxation after initial precontraction during immune degranulation with AA; intravenous chlorpheniramine (5 mg/kg) caused 69.7 +/- 9.4% relaxation. We demonstrate a model that permits selective immune degranulation of a single major resistance bronchus in situ. We conclude that AA-induced degranulation in dogs caused bronchial contraction predominantly by secretion of preformed mediator.


1987 ◽  
Vol 63 (5) ◽  
pp. 2008-2014 ◽  
Author(s):  
T. M. Murphy ◽  
N. M. Munoz ◽  
C. A. Hirshman ◽  
J. S. Blake ◽  
A. R. Leff

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.


1988 ◽  
Vol 65 (2) ◽  
pp. 721-727 ◽  
Author(s):  
K. Stuart-Smith ◽  
P. M. Vanhoutte

The effect of epithelium removal on the responses of porcine airways to exogenously applied agonists and nerve stimulation was examined. Paired rings of third- (segmental), fourth- and fifth-order (subsegmental) bronchi, with and without epithelium, were placed in organ chambers in physiological salt solution (95% O2-5% CO2, 37 degrees C). Removal of the epithelium caused a leftward shift in the concentration-effect curve for acetylcholine (3rd and 4th order). A similar shift occurred for histamine (3rd and 5th order). The relaxation to isoproterenol was reduced by epithelium removal in a similar fashion in the three orders. Removal of the epithelium reduced the maximal response to KCl (3rd and 4th order) and acetylcholine (5th order). The peak response to nerve stimulation showed a significant rightward shift in the absence of epithelium. In fifth-order bronchi, tissues with epithelium showed a significantly greater degree of fade of the response to sustained electrical stimulation. Thus both epithelium-derived relaxing and contracting factors may be released in porcine airways.


1992 ◽  
Vol 263 (3) ◽  
pp. L402-L408 ◽  
Author(s):  
Y. Gao ◽  
P. M. Vanhoutte

The present study was design to determine the role of prostaglandin E2 and I2 in the responses of isolated canine airways to H2O2. Rings of canine third-order bronchi, some of which had undergone mechanical denudation of the epithelium, were suspended in organ chambers; isometric tension was recorded. During contractions to acetylcholine, H2O2 induced concentration-dependent relaxations. The relaxations were attenuated significantly by indomethacin, acetylsalicylic acid, and methylene blue. H2O2 increased the release of prostaglandin E2 and 6-keto-prostaglandin F1 alpha and the content of adenosine 3',5'-cyclic monophosphate (cAMP). These effects were abolished by indomethacin or methylene blue. H2O2 did not affect the content of guanosine 3',5'-cyclic monophosphate significantly. These observations suggest that 1) H2O2 relaxes canine bronchial smooth muscle and 2) elevation of tissue content of cAMP induced by prostaglandin E2 and I2 may be involved. These phenomena did not appear to be modulated by the respiratory epithelium, since H2O2-induced relaxations and increases in the release of PGE2 and 6-ketoprostaglandin F1 alpha were similar in preparations with and without epithelium. However, after treatment with methylene blue, H2O2 induced contractions only in preparations with epithelium. These epithelium-dependent contractions were not affected by inhibitors of cyclooxygenase and lipoxygenase.


1989 ◽  
Vol 67 (1) ◽  
pp. 174-180 ◽  
Author(s):  
T. M. Murphy ◽  
R. W. Mitchell ◽  
J. S. Blake ◽  
M. M. Mack ◽  
E. A. Kelly ◽  
...  

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.


2006 ◽  
Vol 147 (4) ◽  
pp. 371-378 ◽  
Author(s):  
Rodolfo Rodriguez ◽  
Rosa Ventura-Martinez ◽  
Jacinto Santiago-Mejia ◽  
Maria R Avila-Costa ◽  
Teresa I Fortoul

1996 ◽  
Vol 271 (4) ◽  
pp. L631-L636 ◽  
Author(s):  
E. Roux ◽  
C. Guibert ◽  
H. Crevel ◽  
J. P. Savineau ◽  
R. Marthan

We previously reported that NO2 and acrolein administered ex vivo to the lung altered the subsequent responsiveness of airway smooth muscle. The aim of this study was to determine the dose-response relationship for O3 in both human isolated bronchi and rat tracheae and to investigate the mechanisms underlying O3-induced airway responsiveness. Exposure to 1 ppm O3 for 15 min significantly increased the maximal response to carbachol of rat tracheal rings to 149.6 +/- 5.4% of the reference response to acetylcholine (ACh) compared with that of unexposed rings (131.3 +/- 2.4%, n = 6, P < 0.05). The change in maximal airway responsiveness to carbachol, when plotted against the product of exposure concentration and exposure time to O3, a surrogate for the dose, formed a bell-shaped curve. The peak of this dose-response curve was shifted to the right for human bronchi (50 ppm x min, n = 5) compared with that of rat tracheae (15 ppm x min, n = 6). In the rat trachea, responses to KCl were not altered by O3, whereas those to 5-hydroxytryptamine hydrochloride (5-HT) were significantly increased. Finally, in the absence of external Ca2+, O3 exposure still potentiated the maximal response to carbachol from 73.6 +/- 13.9 to 137.0 +/- 6.0% and that to 5-HT from 21.5 +/- 5.5 to 38.7 +/- 2.2% of the reference ACh response. These results indicate that O3 alters the subsequent in vitro airway responsiveness depending on 1) the dose, 2) the nature of the agonist, and 3) the species investigated. Because in vitro exposure to O3 increases responses to agonists that release intracellular Ca2+ and since this effect is maintained in Ca(2+)-free solution, the mechanism of O3-induced increase in airway smooth muscle responsiveness is likely to involve an enhancement in intracellular Ca2+ release.


1932 ◽  
Vol 7 (1) ◽  
pp. 477-494 ◽  
Author(s):  
MARGARET E. SAWYER

A study has been made of the anatomical relations and function of a large sheet of smooth muscle lying in the anterior mesentery of elasmobranchs. This muscle acts on the spiral intestine, pulling it anteriorly and at the same time causing a marked rotation of the intestine towards the right. Its contraction is produced by direct mechanical or electrical stimulation, by stretching and by sympathetic and parasympathetic drugs. It is doubtful whether the mesenteric muscle is under the control of extrinsic sympathetic or parasympathetic nerves since stimulation of these produces a contraction only when there is simultaneous activity in the stomach or intestine. The contraction in this latter case could be due to a secondary stimulation produced by mechanical or tension effects. It is thought that this muscle acts as a mechanism for regulating the position of the spiral intestine during digestion.


1983 ◽  
Vol 55 (1) ◽  
pp. 113-120 ◽  
Author(s):  
A. R. Leff ◽  
N. M. Munoz ◽  
S. G. Hendrix

We compared the sympathetic and parasympathetic contractile responses of tracheal and third-order bronchial smooth muscle simultaneously in 26 dogs in situ. Stimulus-response curves were generated by bilateral stimulation of the cervical vagus nerves in five dogs to determine the parameters (20 V, 15 Hz, 2-ms duration) causing maximal parasympathetic contraction in trachea and bronchus. In six adrenal-intact (ADi) and five adrenalectomized (ADx) dogs, sympathetically mediated alpha-adrenergic contraction was studied after muscarinic and beta-adrenergic blockade by administering intravenous (iv) 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). In ADi dogs, the maximal alpha-adrenergic contractile response to iv DMPP was 67.3 +/- 14.8% of the maximal parasympathetic response in trachea and 112 +/- 21% of the maximal parasympathetic response in bronchus (P less than 0.03). In ADx dogs, the maximal alpha-adrenergic-to-parasympathetic stimulation ratios were 17.6 +/- 1.3% in trachea and 41.4 +/- 2.5% in bronchus (P less than 0.001). Comparable relationships were also obtained in pharmacological studies of alpha-adrenergic and cholinergic responses in trachea and bronchus. We conclude that there is substantial heterogeneity in the physiological and pharmacological cholinergic and alpha-adrenergic contractile properties in trachea and bronchus. Relative to cholinergic contraction, both circulating catecholamines and sympathetic innervation cause substantially greater alpha-adrenergic contraction in bronchus than for tracheal smooth muscle.


1972 ◽  
Vol 57 (3) ◽  
pp. 661-671
Author(s):  
NOZOMU HISANO ◽  
HIDEKI TATEDA ◽  
MASUTARO KUWABARA

1. The distribution of the axons of the photo-excitative neurones in Onchidium verruculatum has been traced by intracellular stimulation of the soma and extracellular stimulation of the axon. They send axon branches mainly into the pleuroparietal and abdominal nerves in both sides. 2. In the whole-animal preparation, photo-excitative spikes could be recorded from neither the soma nor the nerves of inherently photo-excitative neurones during light stimulation. ‘On’ and ‘off’ spikes were initiated only immediately after the beginning and the cessation of illumination of a whole animal. 3. ‘Off’ spikes originated from dorsal eyes and stalk eyes to which shadow stimuli were applied. Those spikes were not the direct response of photo-excitative neurones to light. 4. The excitation of the inherently photo-excitative neurones in situ was suppressed by inhibitory inputs coming through the right and left pleuro-parietal nerves. Cutting one (or some) of the pleuro-parietal nerves was the only condition that diminished the inhibitory inputs to the photo-excitative neurones in the present work. Adequate electrical stimulation of the pleuro-parietal nerves inhibited spikes of photo-excitative neurones due to photo-excitator or spontaneous discharge.


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