Absence of nonadrenergic noncholinergic relaxation in the cat cervical trachea

1988 ◽  
Vol 65 (6) ◽  
pp. 2524-2530 ◽  
Author(s):  
H. Don ◽  
D. G. Baker ◽  
C. A. Richardson
Keyword(s):  
Smooth Muscle ◽  
Vagal Stimulation ◽  
Muscle Tone ◽  
Dynamic Compliance ◽  
Tracheal Mucosa ◽  
In Vivo Experiments ◽  
Lower Airways ◽  
Cervical Trachea

Published in vivo experiments have not supported in vitro reports of the presence of nonadrenergic noncholinergic (NANC) inhibitory pathways in the cat trachea. We therefore examined these pathways, measuring tension in an innervated tracheal segment, flow resistance in more distal airways, and dynamic compliance, in 10 anesthetized mechanically ventilated cats. Initially, cervical vagal stimulation evoked contraction followed by relaxation of smooth muscle of trachea and lower airways; sympathetic stimulation evoked relaxation only. After muscarinic blockade and restoration of smooth muscle tone with 5-hydroxytryptamine (5-HT) applied topically to the tracheal mucosa, vagal stimulation did not affect tracheal segment tension, whereas sympathetic-evoked relaxation was preserved. Similar results were found when tone was restored with intravenous 5-HT, with vagal stimulation also decreasing resistance and increasing compliance. We conclude that NANC pathways are present in lower airways but not in the cervical trachea of the cat. We hypothesize that parasympathetic constriction of cat airway smooth muscle can occur without simultaneous NANC activation, whereas NANC activity occurs only in tandem with parasympathetic stimulation.

Inhibition of dihydropyridine-sensitive calcium entry in hypoxic relaxation of airway smooth muscle

1995 ◽  
Vol 268 (2) ◽  
pp. L201-L206 ◽  
Author(s):  
C. Vannier ◽  
T. L. Croxton ◽  
L. S. Farley ◽  
C. A. Hirshman
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Bay K 8644 ◽  
O2 Concentration ◽  
Voltage Dependent ◽  
Progressive Hypoxia ◽  
Carbamyl Choline

Hypoxia dilates airways in vivo and reduces active tension of airway smooth muscle in vitro. To determine whether hypoxia impairs Ca2+ entry through voltage-dependent channels (VDC), we tested the ability of dihydropyridines to modulate hypoxia-induced relaxation of KCl- and carbamyl choline (carbachol)-contracted porcine bronchi. Carbachol- or KCl-contracted bronchial rings were exposed to progressive hypoxia in the presence or absence of 1 microM BAY K 8644 (an L-type-channel agonist). In separate experiments, rings were contracted with carbachol or KCl, treated with nifedipine (a VDC antagonist), and finally exposed to hypoxia. BAY K 8644 prevented hypoxia-induced relaxation in KCl-contracted bronchi. Nifedipine (10(-5) M) totally relaxed KCl- contracted bronchi. Carbachol-contracted bronchi were only partially relaxed by nifedipine but were completely relaxed when the O2 concentration of the gas was reduced from 95 to 0%. These data indicate that hypoxia can reduce airway smooth muscle tone by limiting entry of Ca2+ through a dihydropyridine-sensitive pathway, but that other mechanisms also contribute to hypoxia-induced relaxation of carbachol-contracted bronchi.

Airway smooth muscle tone increases airway responsiveness in healthy young adults

2017 ◽  
Vol 312 (3) ◽  
pp. L348-L357 ◽  
Author(s):  
Morgan Gazzola ◽  
Katherine Lortie ◽  
Cyndi Henry ◽  
Samuel Mailhot-Larouche ◽  
David G. Chapman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Airway Responsiveness ◽  
High Dose ◽  
Forced Oscillation Technique ◽  
Single High Dose ◽  
Healthy Humans

Force adaptation, a process whereby sustained spasmogenic activation (viz., tone) of airway smooth muscle (ASM) increases its contractile capacity, has been reported in isolated ASM tissues in vitro, as well as in mice in vivo. The objective of the present study was to assess the effect of tone on airway responsiveness in humans. Ten healthy volunteers underwent methacholine challenge on two occasions. One challenge consisted of six serial doses of saline followed by a single high dose of methacholine. The other consisted of six low doses of methacholine 5 min apart followed by a higher dose. The cumulative dose was identical for both challenges. After both methacholine challenges, subjects took a deep inspiration (DI) to total lung capacity as another way to probe ASM mechanics. Responses to methacholine and the DI were measured using a multifrequency forced oscillation technique. Compared with a single high dose, the challenge preceded by tone led to an elevated response measured by respiratory system resistance (Rrs) and reactance at 5 Hz. However, there was no difference in the increase in Rrs at 19 Hz, suggesting a predominant effect on smaller airways. Increased tone also reduced the efficacy of DI, measured by an attenuated maximal dilation during the DI and an increased renarrowing post-DI. We conclude that ASM tone increases small airway responsiveness to inhaled methacholine and reduces the effectiveness of DI in healthy humans. This suggests that force adaptation may contribute to airway hyperresponsiveness and the reduced bronchodilatory effect of DI in asthma.

Effects of Triazoles on Smooth Muscle Tone and Immunologically Released Bronchoconstrictive Mediators in Vitro and in Vivo

2009 ◽  
Vol 55 (5) ◽  
pp. 418-421
Author(s):  
Rolf G. G. Andersson ◽  
Nils Grundström ◽  
Susan Hedman ◽  
Lars Sörenby ◽  
Jarl E. S. Wikberg
Keyword(s):  
Smooth Muscle ◽  
Muscle Tone ◽  
Smooth Muscle Tone

Second Place — Resident Basic Science Award 1993: Mucociliary Function and Endothelins 1, 2, and 3

1993 ◽  
Vol 109 (4) ◽  
pp. 634-645 ◽  
Author(s):  
Finn R. Amble ◽  
Sven O. H. Lindberg ◽  
Thomas V. McCaffrey ◽  
Thomas Runer
Keyword(s):  
Normal Mucosa ◽  
Tracheal Mucosa ◽  
Active Peptides ◽  
Inflammatory Conditions ◽  
Mucociliary System ◽  
Mucociliary Function ◽  
Lower Airways ◽  
Respiratory Homeostasis

Endothelins are recently discovered peptides that cause vasoconstriction and bronchoconstriction. The significance to the mucociliary system of endothelins (ET) 1, 2 and 3 in upper as well as lower airways has not yet been clarified. Effects of these active peptides were investigated, combining both in vitro and in vivo rabbit models of mucociliary activity from the maxillary sinus and the trachea. The studies were performed using computerized photometric microscopy. Immunohistologic staining procedures were used to determine the presence of endothelins in sinus and trachea epithelium. Significant effects on mucociliary activity were noted for ET-1, −2, and −3 in vitro as well as in vivo. All endothelins were noted to accelerate mucociliary activity of both sinus and tracheal mucosa. The effects of endothelins were greater in the sinus than in the trachea. In vitro studies using the calcium blocker nifedipine and the cyclooxygenase inhibitor diclofenac indicated that the mechanism of action involves an intermediary prostaglandin pathway but is independent of release of intracellular calcium. These results were confirmed using ET-1 in vivo. Immunohistochemical staining showed endothelin to be present in both maxillary and tracheal epithelium of the rabbit. We conclude that endothelins have significant mucociliary stimulatory effects and that the presence of endothelins in normal mucosa indicates a potentially important role in respiratory homeostasis as well as inflammatory conditions

Effect of vagal stimulation and parenteral acetylcholine on canine trachealis muscle shortening

1992 ◽  
Vol 72 (6) ◽  
pp. 2463-2468 ◽  
Author(s):  
M. Okazawa ◽  
Y. Wakai ◽  
S. Osborne ◽  
P. D. Pare ◽  
J. D. Road
Keyword(s):  
Smooth Muscle ◽  
Nerve Stimulation ◽  
Vagal Stimulation ◽  
Vagal Nerve ◽  
Vagal Nerve Stimulation ◽  
Local Injection ◽  
Systemic Injection ◽  
Muscle Shortening

Canine trachealis smooth muscle shortening (TMS) in response to vagal nerve stimulation is approximately 30%, far less than the 70% predicted from in vitro studies. We hypothesized that in vivo airway smooth muscle activation during vagal stimulation may be submaximal, and in this study we wished to determine TMS during maximal activation. TMS was studied in 12 alpha-chloralose-anesthetized dogs during vagal stimulation, systemic acetylcholine injection, and local acetylcholine injection. Bilateral vagal stimulation produced TMS of 26 +/- 5% (SE) length at functional residual capacity (LFRC). Maximal TMS during systemic injection of acetylcholine was 28 +/- 12% LFRC but may have been limited by delivery of acetylcholine to the muscle because asystole occurred at higher concentrations. TMS was greatest during local injection of acetylcholine (48 +/- 7% LFRC). There was a greater increase in pulmonary resistance and decrease in dynamic compliance during systemic acetylcholine injection than during vagal stimulation. We conclude that bilateral vagal nerve stimulation does not maximally activate trachealis smooth muscle but that the maximal shortening achieved with local injection of acetylcholine is still less than isotonic shortening in vitro. These data suggest that maximal shortening in vivo is limited by the afterload provided by the tracheal cartilaginous rings.

scholarly journals AB302. SPR-29 Sphingosine-1-phosphate in vitro and in vivo modulates corpus cavernosum smooth muscle tone

2016 ◽  
Vol 5 (S2) ◽  
pp. AB302-AB302
Author(s):  
Xinhua Zhang ◽  
Jing Yin ◽  
Nirmala D. Kanika ◽  
Yuehong Tong ◽  
Guillermo Villegas ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Tone ◽  
Corpus Cavernosum ◽  
Smooth Muscle Tone ◽  
Sphingosine 1 Phosphate

Eosinophils, major basic protein, and polycationic peptides augment bovine airway myocyte Ca2+mobilization

1998 ◽  
Vol 274 (6) ◽  
pp. L997-L1005 ◽  
Author(s):  
Mark E. Wylam ◽  
Nesli Gungor ◽  
Richard W. Mitchell ◽  
Jason G. Umans
Keyword(s):  
Smooth Muscle ◽  
Basic Protein ◽  
Muscle Tone ◽  
Dependent Manner ◽  
Major Basic Protein ◽  
Human Eosinophil ◽  
Intracellular Ca ◽  
Airway Tone

Previous studies in vivo or in isolated airway preparations have suggested that eosinophil-derived polycationic proteins enhance airway smooth muscle tone in an epithelium-dependent manner. We assessed the direct effects of activated human eosinophil supernatant, major basic protein (MBP), and polycationic polypeptides on basal and agonist-stimulated intracellular Ca2+concentrations ([Ca2+]i) in cultured bovine tracheal smooth muscle (TSM) cells. A 1-h incubation of myocytes with activated eosinophil buffer resulted in a doubling of basal [Ca2+]iand increased responsivity to histamine compared with myocytes that were exposed to sham-activated eosinophil buffer. In addition, concentration-dependent acute transient increases and subsequent 1-h sustained elevations of basal [Ca2+]iwere observed immediately after addition of MBP and model polycationic proteins. Finally, both peak and plateau [Ca2+]iresponses to bradykinin addition were augmented significantly in cultured myocytes that had been exposed to low concentrations of MBP or model polycationic proteins but were inhibited at greater concentrations. This elevated [Ca2+]ito polycationic proteins was manifest in epithelium-denuded bovine TSM strips as concentration-dependent increased basal tone. We conclude that activated eosinophil supernatant, MBP, and other polycationic proteins have a direct effect on both basal and subsequent agonist-elicited Ca2+mobilization in cultured TSM cells; TSM strips in vitro demonstrated, respectively, augmented and diminished responses to the contractile agonist acetylcholine. It is possible that alteration in myocyte Ca2+mobilization induced by these substances may influence clinical states of altered airway tone, such as asthma.

Abstract 532: The RNA-binding Protein Quaking Critically Regulates Vascular Smooth Muscle Cell Phenotype

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Eric P van der Veer ◽  
Ruben G de Bruin ◽  
Adriaan O Kraaijeveld ◽  
Margreet R de Vries ◽  
Tonio Pera ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Injury ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Decisive Role ◽  
Cell Phenotype ◽  
In Vivo Experiments

In response to vascular injury, smooth muscle cells (VSMC) adopt a proliferative, synthetic hypocontractile phenotype. This phenotype switch is deemed instrumental in vascular remodeling in both health and disease. Here, we detail a decisive role for the RNA-binding protein Quaking (QKI) in regulating VSMC plasticity. We identified that the RNA-binding protein Quaking (QKI) is highly expressed by neointimal VSMCs of human coronary restenotic lesions, but not in healthy vessels. In a mouse model of vascular injury, we observed reduced neointima hyperplasia in Qk v mice, which have decreased QKI expression. Concordantly, abrogation of QKI attenuated fibroproliferative properties of VSMCs, while potently inducing contractile apparatus protein expression, rendering non-contractile VSMCs with the capacity to contract. We identified that QKI localizes to the spliceosome in proliferative VSMCs, where it interacts with and impacts myocardin (pre)-mRNA metabolism by mediating myocardin exon 2a exclusion. As such, in vitro and in vivo experiments indicate that the modulation of QKI expression directly influences the myocardin_v3 / myocardin_v1 mRNA balance, which could play a role in shifting the Myocardin-induced transcriptional coactivation profile following arterial damage. We propose that QKI is a central regulator of VSMC phenotypic plasticity and that intervention in QKI activity can ameliorate pathogenic, fibroproliferative responses to vascular injury.

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