Effect of Sodium-Transport Inhibitors on Airway Smooth Muscle Contractility in Vitro

1990 ◽  
Vol 79 (4) ◽  
pp. 315-323 ◽  
Author(s):  
Alan J. Knox ◽  
Paul Ajao ◽  
John R. Britton ◽  
Anne E. Tattersfield
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Sodium Transport ◽  
Maximum Response ◽  
Maximum Effect ◽  
Free Fluid ◽  
Smooth Muscle Contractility ◽  
Voltage Dependent ◽  
Histamine Response

1. To determine whether alterations in membrane sodium transport in airway smooth muscle can alter its contractility, we studied the effect of ouabain (a Na+/K+-adenosine triphosphatase inhibitor) and amiloride on contractile responses in bovine trachea and human bronchial rings in a series of studies. 2. Ouabain (10−6–10−4 mol/l) caused concentration-related contraction of bovine trachea with a maximum effect at 30 min; the mean increases in tension with 10−6, 10−5 and 10−4 mol/l ouabain were 19, 27, and 32%, respectively, of the maximum response seen with 10−3 mol/l histamine (n = 6). In human bronchial rings, ouabain (10−5 mol/l) caused a mean contraction which was 40% of the maximum response to methacholine (n = 8). 3. Calcium-free fluid (plus ethylenediaminetetra-acetic acid) and nifedipine (10−5 mol/l) inhibited ouabain-induced contractions, suggesting that contraction was mediated in part by calcium entry via voltage-dependent calcium channels. Phentolamine (10−5 mol/l) was without effect. 4. Ouabain (10−5 mol/l) did not alter histamine responsiveness in bovine trachea or methacholine responsiveness in human bronchial rings. 5. Amiloride did not affect resting tone in bovine trachea but caused a concentration-dependent relaxation of bovine tracheal strips preconstricted with carbachol, 10−3 mol/l amiloride relaxing strips completely over 15 minutes (n = 8). Pretreatment with amiloride significantly inhibited contraction produced by both histamine and carbachol in a dose-related manner, 10−5, 10−4 and 10−3 mol/l amiloride shifting the concentration of histamine producing 50% maximal contraction by 3-, 8- and 35-fold (n = 10) and that of carbachol by 1.4-, 6- and 86-fold (n = 8), respectively. 6. Amiloride also reduced the contraction produced by 10−4 mol/l ouabain from 32% (control) to 7% of the maximum histamine response. 7. Our results suggest that alterations in cell membrane sodium transport modify the contractile properties of airway smooth muscle.

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.

Interleukin-1β-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway

2002 ◽  
Vol 283 (5) ◽  
pp. L909-L917 ◽  
Author(s):  
Z.-X. Wu ◽  
B. E. Satterfield ◽  
J. S. Fedan ◽  
R. D. Dey
Keyword(s):  
Smooth Muscle ◽  
Substance P ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Sensory Nerves ◽  
Tracheal Smooth Muscle ◽  
Fiber Density ◽  
Smooth Muscle Contractility ◽  
Neurokinin 1

Interleukin (IL)-1β causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1β. Ferrets were instilled intratracheally with IL-1β (0.3 μg/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and substance P (SP) expression in tracheal neurons were assessed. Tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) and smooth muscle contractions to electric field stimulation (EFS) both increased after IL-1β. The IL-1β-induced AHR was maintained in tracheal segments cultured for 24 h, a procedure that depletes SP from sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the IL-1β-induced hyperreactivity to ACh and MCh and to EFS in cultured tracheal segments. SP-containing neurons in longitudinal trunk, SP innervation of superficial muscular plexus neurons, and SP nerve fiber density in tracheal smooth muscle all increased after treatment with IL-1β. These results show that IL-1β-enhanced cholinergic airway smooth muscle contractile responses are mediated by the actions of SP released from intrinsic airway neurons.

scholarly journals VIP/PACAP Signaling as an Alternative Target During Hyperoxic Exposure in Preterm Newborns

2021 ◽  
pp. 489-499
Author(s):  
Qëndrim Thaçi ◽  
Shkëlzen Reçica ◽  
Islam Kryeziu ◽  
Vadim Mitrokhin ◽  
Andre Kamkin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Adenylate Cyclase ◽  
Airway Smooth Muscle ◽  
Smooth Muscle Relaxation ◽  
Smooth Muscle Contractility ◽  
Hyperoxic Exposure ◽  
Airway Caliber ◽  
Pituitary Adenylate Cyclase ◽  
Preterm Newborns

The use of oxygen therapy (high doses of oxygen - hyperoxia) in the treatment of premature infants results in their survival. However, it also results in a high incidence of chronic lung disease known as bronchopulmonary dysplasia, a disease in which airway hyper-responsiveness and pulmonary hypertension are well known as consequences. In our previous studies, we have shown that hyperoxia causes airway hyper-reactivity, characterized by an increased constrictive and impaired airway smooth muscle relaxation due to a reduced release of relaxant molecules such as nitric oxide, measured under in vivo and in vitro conditions (extra- and intrapulmonary) airways. In addition, the relaxation pathway of the vasoactive intestinal peptide (VIP) and/or pituitary adenylate cyclase activating peptide (PACAP) is another part of this system that plays an important role in the airway caliber. Peptide, which activates VIP cyclase and pituitary adenylate cyclase, has prolonged airway smooth muscle activity. It has long been known that VIP inhibits airway smooth muscle cell proliferation in a mouse model of asthma, but there is no data about its role in the regulation of airway and tracheal smooth muscle contractility during hyperoxic exposure of preterm newborns.

Hyperoxic exposure enhances airway reactivity of newborn guinea pigs

1993 ◽  
Vol 74 (6) ◽  
pp. 2649-2654 ◽  
Author(s):  
C. F. Uyehara ◽  
B. E. Pichoff ◽  
H. H. Sim ◽  
H. S. Uemura ◽  
K. T. Nakamura
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Guinea Pigs ◽  
Airway Hyperreactivity ◽  
Muscle Contractility ◽  
Airway Reactivity ◽  
Smooth Muscle Contractility ◽  
Contractile Responses ◽  
Hyperoxic Exposure

To determine whether altered airway smooth muscle contractility contributes to airway hyperreactivity resulting from hyperoxic exposure, in vitro contractile responses of airways to two physiological constrictors, acetylcholine (10(-9) to 10(-4) M) and histamine (10(-8) to 10(-4) M), were examined. Extrathoracic trachea, intrathoracic trachea, and bronchus from 1- to 2-day-old (newborn) guinea pigs exposed to 85% oxygen for 84 h were compared with tissues obtained from newborns reared in room air. Responses in the presence and absence of aspirin (ASA; 10(-3) M) were compared. Hyperoxic exposure did not affect the histology of the airway epithelia. Contractile responses to acetylcholine and histamine were similar. Without ASA, maximal tensions generated were higher in both extrathoracic and intrathoracic trachea obtained from hyperoxia-exposed neonates than in trachea from newborns reared in room air. ASA caused maximal tensions of trachea from newborns reared in room air to increase but did not affect the already increased contractility of trachea from hyperoxia-exposed animals; the tensions achieved in hyperoxic tissues with and without ASA were similar to the hyperactive responses induced by ASA in tissues from animals reared in room air. Bronchi showed responses similar to those seen in tracheal segments. Thus, despite no apparent histological effect on the airway epithelium, hyperoxic exposure seems to increase airway smooth muscle contractility, is nonspecific for different constricting agents, and shows no regional differences in airway reactivity.

Enhanced nitric oxide production associated with airway hyporesponsiveness in the absence of IL-10

2005 ◽  
Vol 288 (5) ◽  
pp. L868-L873 ◽  
Author(s):  
Bill T. Ameredes ◽  
Jigme M. Sethi ◽  
He-Liang Liu ◽  
Augustine M. K. Choi ◽  
William J. Calhoun
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Tracheal Ring ◽  
No Production ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Nos Inhibitors

Interleukin (IL)-10 is an anti-inflammatory cytokine implicated in the regulation of airway inflammation in asthma. Among other activities, IL-10 suppresses production of nitric oxide (NO); consequently, its absence may permit increased NO production, which can affect airway smooth muscle contractility. Therefore, we investigated airway reactivity (AR) in response to methacholine (MCh) in IL-10 knockout (−/−) mice compared with wild-type C57BL/6 (C57) mice, in which airway NO production was measured as exhaled NO (ENO), and NO production was altered with administration of either NO synthase (NOS)-specific inhibitors or recombinant murine (rm)IL-10. AR, measured as enhanced pause in vivo, and tracheal ring tension in vitro were lower in IL-10−/− mice by 25–50%, which was associated with elevated ENO levels (13 vs. 7 ppb). Administration of NOS inhibitors NG-nitro-l-arginine methyl ester (8 mg/kg ip) or l- N6-(1-iminoethyl)-lysine (3 mg/kg ip) to IL-10−/− mice decreased ENO by an average of 50%, which was associated with increased AR, to levels similar to C57 mice. ENO in IL-10−/− mice decreased in a dose-dependent fashion in response to administered rmIL-10, to levels similar to C57 mice (7 ppb), which was associated with a 30% increment in AR. Thus increased NO production in the absence of IL-10, decreased AR, which was reversed with inhibition of NO, either by inhibition of NOS, or with reconstitution of IL-10. These findings suggest that airway NO production can modulate airway smooth muscle contractility, resulting in airway hyporesponsiveness when IL-10 is absent.

Intracellular pH regulates voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells

1995 ◽  
Vol 268 (4) ◽  
pp. L642-L646 ◽  
Author(s):  
M. Yamakage ◽  
K. S. Lindeman ◽  
C. A. Hirshman ◽  
T. L. Croxton
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Tracheal Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Smooth Muscle Contractility ◽  
Voltage Dependent ◽  
Airway Tone ◽  
Ca2 Channels

Changes in CO2 or in pH modify airway smooth muscle contractility. To investigate the mechanisms involved, we compared K(+)-induced contractions in porcine bronchial rings exposed to different CO2 concentrations and directly measured the effects of changes in intracellular (pHi) or extracellular pH (pHo) on Ca2+ currents (ICa) through voltage-dependent Ca2+ channels (VDC) in porcine tracheal smooth muscle cells. Hypocapnia and hypercapnia caused leftward and rightward shifts, respectively, in the dose-response to K+ (P < 0.05) but did not change the maximum force obtained. Peak ICa (10 mM external Ca2+) elicited by depolarizing pulses from -80 mV was maximal [-265 +/- 12 pA (mean +/- SE), n = 19] at +10 mV. Intracellular acidification decreased the peak ICa at +10 mV from -261 +/- 20 pA to -177 +/- 12 pA (P < 0.05, n = 4), while intracellular alkalinization increased the peak ICa at +10 mV from -302 +/- 27 pA to -368 +/- 26 pA (P < 0.05, n = 4). Changes in pHo had little effect on ICa. There was no shift in the voltage-dependence of induced ICa with any change. We conclude that pHi, but not pHo, directly modulates the entry of Ca2+ into airway smooth muscle cells through VDC. This mechanism may contribute to regulation of airway tone by CO2.

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