Maturation of respiratory reflex responses in the piglet

1991 ◽  
Vol 70 (2) ◽  
pp. 608-616 ◽  
Author(s):  
B. Haxhiu-Poskurica ◽  
W. A. Carlo ◽  
M. J. Miller ◽  
J. M. DiFiore ◽  
M. A. Haxhiu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Phrenic Nerve ◽  
Muscle Tone ◽  
Muscle Tension ◽  
Age Groups ◽  
Force Transducer ◽  
Reflex Responses ◽  
C Fiber ◽  
Lung Deflation

Stimulation of chemo-, irritant, and pulmonary C-fiber receptors reflexly constricts airway smooth muscle and alters ventilation in mature animals. These reflex responses of airway smooth muscle have, however, not been clearly characterized during early development. In this study we compared the maturation of reflex pathways regulating airway smooth muscle tone and ventilation in anesthetized, paralyzed, and artificially ventilated 2- to 3- and 10-wk-old piglets. Tracheal smooth muscle tension was measured from an open tracheal segment by use of a force transducer, and phrenic nerve activity was measured from a proximal cut end of the phrenic nerve. Inhalation of 7% CO2 caused a transient increase in tracheal tension in both age groups, whereas hypoxia caused no airway smooth muscle response in either group. The phrenic responses to 7% CO2 and 12% O2 were comparable in both age groups. Lung deflation and capsaicin (20 micrograms/kg iv) administration did not alter tracheal tension in the younger piglets but caused tracheal tension to increase by 87 +/- 28 and 31 +/- 10%, respectively, in the older animals (both P less than 0.05). In contrast, phrenic response to both stimuli was comparable between ages: deflation increased phrenic activity while capsaicin induced neural apnea. Laryngeal stimulation did not increase tracheal tension but induced neural apnea in both age groups. These data demonstrate that between 2 and 10 wk of life, piglets exhibit developmental changes in the reflex responses of airway smooth muscle situated in the larger airways in response to irritant and C-fiber but not chemoreceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Nicotine-induced respiratory effects of cigarette smoke in dogs

1985 ◽  
Vol 59 (1) ◽  
pp. 64-71 ◽  
Author(s):  
J. J. Hartiala ◽  
C. Mapp ◽  
R. A. Mitchell ◽  
W. M. Gold
Keyword(s):  
Smooth Muscle ◽  
Cigarette Smoke ◽  
Airway Smooth Muscle ◽  
Direct Effect ◽  
Muscle Tone ◽  
Muscle Tension ◽  
Respiratory Center ◽  
Parasympathetic Ganglia ◽  
Arterial Blood ◽  
Nicotine Receptors

We report that nicotine is responsible for both a blood-borne stimulation of the respiratory center and a direct effect on intrathoracic airway tone in dogs. We introduced cigarette smoke into the lungs of donor dogs and injected arterial blood obtained from them into the circulation of recipient dogs to show that a blood-borne material increased breathing and airway smooth muscle tone. Smoke from cigarettes containing 2.64 mg of nicotine was effective; that from cigarettes containing 0.42 mg of nicotine was not. Nicotine, in doses comparable to the amounts absorbed from smoke, also increased breathing and tracheal smooth muscle tension when injected into the vertebral circulation of recipient dogs. Finally, blockade of nicotine receptors in the central nervous system and in the airway parasympathetic ganglia inhibited the effects of inhaled cigarette smoke and intravenous nicotine on the respiratory center and on bronchomotor tone. We conclude that nicotine absorbed from cigarette smoke is the main cause of cigarette smoke-induced bronchoconstriction. It caused central respiratory stimulation, resulting in increased breathing and airway smooth muscle tension, and had a direct effect on airway parasympathetic ganglia as well.

Benzodiazepines acting on ventral surface of medulla cause airway dilation

1989 ◽  
Vol 257 (4) ◽  
pp. R810-R815 ◽  
Author(s):  
M. A. Haxhiu ◽  
E. van Lunteren ◽  
N. S. Cherniack ◽  
E. C. Deal
Keyword(s):  
Smooth Muscle ◽  
Muscle Tone ◽  
Muscle Tension ◽  
Ventral Surface ◽  
Gamma Aminobutyric Acid ◽  
Tracheal Pressure ◽  
Parasympathetic Neurons ◽  
Lung Deflation ◽  
Airway Tone ◽  
Alpha Chloralose

The benzodiazepines that have anxiolytic, anticonvulsant, muscle-relaxant, and sedative-hypnotic properties affect respiration possibly by acting on gamma-aminobutyric acid (GABA)ergic receptors. This study investigated the effects of benzodiazepines diazepam and midazolam) applied topically to or microinjected just beneath the ventrolateral medullary surface (VMS) on airway tone in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats. Trachealis smooth muscle tension was assessed by measuring the changes in pressure in a balloon placed in a bypassed rostral segment of the trachea. In 21 cats ventilated with 7% CO2 in O2, surface application of benzodiazepines caused a significant decrease in tracheal tone. Similar to topical application, microinjection of midazolam (1 microgram) in the ventral medulla (0.1-0.2 mm from the surface) in six cats decreased tracheal pressure by 13.2 +/- 2.1 cmH2O (P less than 0.01). In addition, application of benzodiazepines on the VMS in animals ventilated with 12% O2 in N2 (n = 5) decreased tracheal pressure from 15.9 +/- 2.2 to 5.2 +/- 2.7 cmH2O (P less than 0.05). Furthermore, in all cats studied (n = 6), the magnitude of lung deflation-induced tracheal contraction was reduced after application of benzodiazepines on the ventral surface of the medulla (from 11.4 +/- 1.6 to 2.2 +/- 0.9 cmH2O; P less than 0.01). The effects of benzodiazepines on tracheal tone were reversed and blocked by application of Ro 15-1788, a specific benzodiazepines antagonist. However, when parasympathetic activity was abolished by atropine and tracheal tone was restored with 5-hydroxytryptamine, benzodiazepines applied on the VMS had no effect on tracheal pressure. These results suggest that benzodiazepines acting centrally, on structures located near the VMS, can cause a decrease in airway smooth muscle tone by diminishing the activity of parasympathetic neurons which project to the airways.

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.

scholarly journals Methacholine causes reflex bronchoconstriction

1999 ◽  
Vol 86 (1) ◽  
pp. 294-297 ◽  
Author(s):  
Elizabeth M. Wagner ◽  
David B. Jacoby
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Bronchial Artery ◽  
Muscle Tension ◽  
Reflex Response ◽  
Resistance Change ◽  
Bilateral Vagotomy ◽  
Airways Resistance ◽  
Lower Airways

To determine whether methacholine causes vagally mediated reflex constriction of airway smooth muscle, we administered methacholine to sheep either via the bronchial artery or as an aerosol via tracheostomy into the lower airways. We then measured the contraction of an isolated, in situ segment of trachealis smooth muscle and determined the effect of vagotomy on the trachealis response. Administering methacholine to the subcarinal airways via the bronchial artery (0.5–10.0 μg/ml) caused dose-dependent bronchoconstriction and contraction of the tracheal segment. At the highest methacholine concentration delivered, trachealis smooth muscle tension increased an average of 186% over baseline. Aerosolized methacholine (5–7 breaths of 100 mg/ml) increased trachealis tension by 58% and airways resistance by 183%. As the bronchial circulation in the sheep does not supply the trachea, we postulated that the trachealis contraction was caused by a reflex response to methacholine in the lower airways. Bilateral vagotomy essentially eliminated the trachealis response and the airways resistance change after lower airways challenge (either via the bronchial artery or via aerosol) with methacholine. We conclude that 1) methacholine causes a substantial reflex contraction of airway smooth muscle and 2) the assumption may not be valid that a response to methacholine in humans or experimental animals represents solely the direct effect on smooth muscle.

Airway smooth muscle tone modulates mechanically induced cytoskeletal stiffening and remodeling

2005 ◽  
Vol 99 (2) ◽  
pp. 634-641 ◽  
Author(s):  
Linhong Deng ◽  
Nigel J. Fairbank ◽  
Darren J. Cole ◽  
Jeffrey J. Fredberg ◽  
Geoffrey N. Maksym
Keyword(s):  
Smooth Muscle ◽  
Mechanical Stress ◽  
Applied Stress ◽  
Airway Smooth Muscle ◽  
Cell Activation ◽  
Structural Changes ◽  
Muscle Tone ◽  
Residual Effects ◽  
Cell Stiffness ◽  
Functional Changes

The application of mechanical stresses to the airway smooth muscle (ASM) cell causes time-dependent cytoskeletal stiffening and remodeling (Deng L, Fairbank NJ, Fabry B, Smith PG, and Maksym GN. Am J Physiol Cell Physiol 287: C440–C448, 2004). We investigated here the extent to which these behaviors are modulated by the state of cell activation (tone). Localized mechanical stress was applied to the ASM cell in culture via oscillating beads (4.5 μm) that were tightly bound to the actin cytoskeleton (CSK). Tone was reduced from baseline level using a panel of relaxant agonists (10−3 M dibutyryl cAMP, 10−4 M forskolin, or 10−6 M formoterol). To assess functional changes, we measured cell stiffness (G′) using optical magnetic twisting cytometry, and to assess structural changes of the CSK we measured actin accumulation in the neighborhood of the bead. Applied mechanical stress caused a twofold increase in G′ at 120 min. After cessation of applied stress, G′ diminished only 24 ± 6% (mean ± SE) at 1 h, leaving substantial residual effects that were largely irreversible. However, applied stress-induced stiffening could be prevented by ablation of tone. Ablation of tone also inhibited the amount of actin accumulation induced by applied mechanical stress ( P < 0.05). Thus the greater the contractile tone, the greater was applied stress-induced CSK stiffening and remodeling. As regards pathobiology of asthma, this suggests a maladaptive positive feedback in which tone potentiates ASM remodeling and stiffening that further increases stress and possibly leads to worsening airway function.

EETs relax airway smooth muscle via an EpDHF effect: BKCa channel activation and hyperpolarization

2001 ◽  
Vol 280 (5) ◽  
pp. L965-L973 ◽  
Author(s):  
Catherine Benoit ◽  
Barbara Renaudon ◽  
Dany Salvail ◽  
Eric Rousseau
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Molecular Mechanisms ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
Epoxyeicosatrienoic Acids ◽  
Bkca Channel ◽  
Channel Activity ◽  
Cytochrome P 450

Epoxyeicosatrienoic acids (EETs) are produced from arachidonic acid via the cytochrome P-450 epoxygenase pathway. EETs are able to modulate smooth muscle tone by increasing K+ conductance, hence generating hyperpolarization of the tissues. However, the molecular mechanisms by which EETs induce smooth muscle relaxation are not fully understood. In the present study, the effects of EETs on airway smooth muscle (ASM) were investigated using three electrophysiological techniques. 8,9-EET and 14,15-EET induced concentration-dependent relaxations of the ASM precontracted with a muscarinc agonist (carbamylcholine chloride), and these relaxations were partly inhibited by 10 nM iberiotoxin (IbTX), a specific large-conductance Ca2+-activated K+ (BKCa) channel blocker. Moreover, 3 μM 8,9- or 14,15-EET induced hyperpolarizations of −12 ± 3.5 and −16 ± 3 mV, with EC50 values of 0.13 and 0.14 μM, respectively, which were either reversed or blocked on addition of 10 nM IbTX. These results indicate that BKCa channels are involved in hyperpolarization and participate in the relaxation of ASM. In addition, complementary experiments demonstrated that 8,9- and 14,15-EET activate reconstituted BKCa channels at low free Ca2+ concentrations without affecting their unitary conductance. These increases in channel activity were IbTX sensitive and correlated well with the IbTX-sensitive hyperpolarization and relaxation of ASM. Together these results support the view that, in ASM, the EETs act through an epithelium-derived hyperpolarizing factorlike effect.

A GABAergic inhibitory microcircuit controlling cholinergic outflow to the airways

2004 ◽  
Vol 96 (1) ◽  
pp. 260-270 ◽  
Author(s):  
Constance T. Moore ◽  
Christopher G. Wilson ◽  
Catherine A. Mayer ◽  
Sandra S. Acquah ◽  
V. John Massari ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Structural Characteristics ◽  
Nucleus Ambiguus ◽  
Acid Decarboxylase ◽  
Electron Microscopic ◽  
Synaptic Contacts ◽  
Smooth Muscle Tone ◽  
Rostral Nucleus

GABA is the main inhibitory neurotransmitter that participates in the regulation of cholinergic outflow to the airways. We have tested the hypothesis that a monosynaptic GABAergic circuit modulates the output of airway-related vagal preganglionic neurons (AVPNs) in the rostral nucleus ambiguus by using a dual-labeling electron microscopic method combining immunocytochemistry for glutamic acid decarboxylase (GAD) with retrograde tracing from the trachea. We also determined the effects of blockade of GABAA receptors on airway smooth muscle tone. The results showed that retrogradely labeled AVPNs received a significant GAD-immunoreactive (GAD-IR) terminal input. Out of a pooled total of 3,161 synaptic contacts with retrogradely labeled somatic and dendritic profiles, 20.2% were GAD-IR. GAD-IR terminals formed significantly more axosomatic synapses than axodendritic synapses ( P < 0.02). A dense population of GABAergic synaptic contacts on AVPNs provides a morphological basis for potent physiological effects of GABA on the excitability of AVPNs. GAD-IR terminals formed exclusively symmetric synaptic specializations. GAD-IR terminals were significantly larger ( P < 0.05) in both length and width than unlabeled terminals synapsing on AVPNs. Therefore, the structural characteristics of certain nerve terminals may be closely correlated with their function. Pharmacological blockade of GABAA receptors within the rostral nucleus ambiguus increased activity of putative AVPNs and airway smooth muscle tone. We conclude that a tonically active monosynaptic GABAergic circuit utilizing symmetric synapses regulates the discharge of AVPNs.

scholarly journals Role of TRPP2 in mouse airway smooth muscle tension and respiration

2019 ◽  
Vol 317 (4) ◽  
pp. L466-L474 ◽  
Author(s):  
Dacheng Sang ◽  
Suwen Bai ◽  
Sheng Yin ◽  
Sen Jiang ◽  
Li Ye ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Transient Receptor Potential ◽  
Muscle Tension ◽  
Pulmonary Arteries ◽  
Conditional Knockout ◽  
Wild Type ◽  
High Potassium ◽  
Cross Sectional ◽  
Significant Difference

The transient receptor potential polycystin-2 (TRPP2) is encoded by the Pkd2 gene, and mutation of this gene can cause autosomal dominant polycystic kidney disease (ADPKD). Some patients with ADPKD experience extrarenal manifestations, including radiologic and clinical bronchiectasis. We hypothesized that TRPP2 may regulate airway smooth muscle (ASM) tension. Thus, we used smooth muscle- Pkd2 conditional knockout ( Pkd2SM-CKO) mice to investigate whether TRPP2 regulated ASM tension and whether TRPP2 deficiency contributed to bronchiectasis associated with ADPKD. Compared with wild-type mice, Pkd2SM-CKO mice breathed more shallowly and faster, and their cross-sectional area ratio of bronchi to accompanying pulmonary arteries was higher, suggesting that TRPP2 may regulate ASM tension and contribute to the occurrence of bronchiectasis in ADPKD. In a bioassay examining isolated tracheal ring tension, no significant difference was found for high-potassium-induced depolarization of the ASM between the two groups, indicating that TRPP2 does not regulate depolarization-induced ASM contraction. By contrast, carbachol-induced contraction of the ASM derived from Pkd2SM-CKO mice was significantly reduced compared with that in wild-type mice. In addition, relaxation of the carbachol-precontracted ASM by isoprenaline, a β-adrenergic receptor agonist that acts through the cAMP/adenylyl cyclase pathway, was also significantly attenuated in Pkd2SM-CKO mice compared with that in wild-type mice. Thus, TRPP2 deficiency suppressed both contraction and relaxation of the ASM. These results provide a potential target for regulating ASM tension and for developing therapeutic alternatives for some ADPKD complications of the respiratory system or for independent respiratory disease, especially bronchiectasis.

Airway basement membrane perimeter in human airways is not a constant; potential implications for airway remodeling in asthma

2004 ◽  
Vol 97 (2) ◽  
pp. 556-563 ◽  
Author(s):  
Brent E. McParland ◽  
Peter D. Paré ◽  
Peter R. A. Johnson ◽  
Carol L. Armour ◽  
Judith L. Black
Keyword(s):  
Smooth Muscle ◽  
Basement Membrane ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Airway Remodeling ◽  
Organ Bath ◽  
Smooth Muscle Tone ◽  
Asthmatic Patients ◽  
Constant Potential ◽  
Human Airways

Many studies that demonstrate an increase in airway smooth muscle in asthmatic patients rely on the assumption that bronchial internal perimeter ( Pi) or basement membrane perimeter ( Pbm) is a constant, i.e., not affected by fixation pressure or the degree of smooth muscle shortening. Because it is the basement membrane that has been purported to be the indistensible structure, this study examines the assumption that Pbm is not affected by fixation pressure. Pbm was determined for the same human airway segment ( n = 12) fixed at distending pressures of 0 cmH2O and 21 cmH2O in the absence of smooth muscle tone. Pbm for the segment fixed at 0 cmH2O was determined morphometrically, and the Pbm for the same segment, had the segment been fixed at 21 cmH2O, was predicted from knowing the luminal volume and length of the airway when distended to 21 cmH2O (organ bath-derived Pi). To ensure an accurate transformation of the organ bath-derived Pi value to a morphometry-derived Pbm value, had the segment been fixed at 21 cmH2O, the relationship between organ bath-derived Pi and morphometry-derived Pbm was determined for five different bronchial segments distended to 21 cmH2O and fixed at 21 cmH2O ( r2 = 0.99, P < 0.0001). Mean Pbm for bronchial segments fixed at 0 cmH2O was 9.4 ± 0.4 mm, whereas mean predicted Pbm, had the segments been fixed at 21 cmH2O, was 14.1 ± 0.5 mm ( P < 0.0001). This indicates that Pbm is not a constant when isolated airway segments without smooth muscle tone are fixed distended to 21 cmH2O. The implication of these results is that the increase in smooth muscle mass in asthma may have been overestimated in some previous studies. Therefore, further studies are required to examine the potential artifact using whole lungs with and without abolition of airway smooth muscle tone and/or inflation.

Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism

2006 ◽  
Vol 290 (3) ◽  
pp. L526-L533 ◽  
Author(s):  
Irving C. Allen ◽  
John M. Hartney ◽  
Thomas M. Coffman ◽  
Raymond B. Penn ◽  
Jürgen Wess ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Acetylcholine Receptor ◽  
Airway Smooth Muscle ◽  
Muscle Tension ◽  
Muscarinic Acetylcholine Receptor ◽  
Airway Smooth Muscle Cells ◽  
Muscarinic Acetylcholine ◽  
Airway Constriction ◽  
Organ Systems ◽  
Lung Resistance

Thromboxane A2 (TXA2) is a potent lipid mediator released by platelets and inflammatory cells and is capable of inducing vasoconstriction and bronchoconstriction. In the airways, it has been postulated that TXA2 causes airway constriction by direct activation of thromboxane prostanoid (TP) receptors on airway smooth muscle cells. Here we demonstrate that although TXA2 can mediate a dramatic increase in airway smooth muscle constriction and lung resistance, this response is largely dependent on vagal innervation of the airways and is highly sensitive to muscarinic acetylcholine receptor (mAChR) antagonists. Further analyses employing pharmacological and genetic strategies demonstrate that TP-dependent changes in lung resistance and airway smooth muscle tension require expression of the M3 mAChR subtype. These results raise the possibility that some of the beneficial actions of anticholinergic agents used in the treatment of asthma and chronic obstructive pulmonary disease result from limiting physiological changes mediated through the TP receptor. Furthermore, these findings demonstrate a unique pathway for TP regulation of homeostatic mechanisms in the airway and suggest a paradigm for the role of TXA2 in other organ systems.

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