scholarly journals Ligustrazine Inhibits Lung Phosphodiesterase Activity in a Rat Model of Allergic Asthma

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Yajuan Wang ◽  
Huizhi Zhu ◽  
Jiabing Tong ◽  
Zegeng Li

Objectives. This study sought to examine whether ligustrazine was capable of inhibiting phosphodiesterase (PDE) activity and improving lung function in a rat model of asthma. Methods. Rats were initially sensitized using ovalbumin (OVA) and then were challenged daily with aerosolized OVA beginning 14 days later (30 min/day) to generate a rat model of asthma. Changes in airway function following methacholine (MCh) injection were evaluated by monitoring lung resistance ( R L ) and dynamic lung compliance ( C dyn ) values using an AniRes2005 analytic system. In addition, serum IgE was measured via ELISA, while PDE expression was evaluated via qPCR and western blotting. Key Findings. Ligustrazine significantly impaired allergen-induced lung hyperresponsivity and inflammation in this asthma model system. Ligustrazine treatment was also associated with reduced expression of PDEs including PDE4 in the lungs of these rats. Conclusions. Ligustrazine suppresses airway inflammation and bronchial hyperresponsivity in this rat model system, and these changes are associated with decreased PDE expression at the protein and mRNA levels.

PEDIATRICS ◽  
1967 ◽  
Vol 40 (6) ◽  
pp. 962-974
Author(s):  
W. A. Aherne ◽  
K. W. Cross ◽  
E. N. Hey ◽  
Sheila R. Lewis

Detailed lung function studies at the age of 8 months and 1 year are reported for an infant who weighed 992 gm at birth and who developed chronic progressive pulmonary insufficiency 2 weeks after birth. The symptoms and signs were similar to those described by Wilson and Mikity in 1960. A confirmatory lung biopsy was obtained when the child was 11 months old. Dynamic lung "compliance" was very significantly reduced while a static estimate of lung compliance was within normal limits. These and other lung function findings are interpreted as indicating that uneven alveolar ventilation was the probable functional basis for all the signs and symptoms observed.


1979 ◽  
Vol 47 (2) ◽  
pp. 418-424 ◽  
Author(s):  
J. W. Ramsdell ◽  
P. F. Georghiou

We studied the effect of prolonged airways obstruction induced by extended cholinergic stimulation in five anesthetized, mechanically ventilated dogs. A continuous intravenous metacholine infusion was utilized to maintain pulmonary resistance (RL) at 200--1500% preinfusion levels for 13--23 h. At maximum RL (18.86 +/- 7.74 vs. 2.09 +/- 0.18 (mean +/- SD) cmH2O/ (L/S) PREINfusion; P less than 0.01), dynamic lung compliance (Cdyn) fell from 67.5 +/- 14.6 to 32.7 +/- 11.6 ml/cmH2O (P less than 0.005) and arterial partial pressure of oxygen (PaO2) fell modestly from 95.8 +/- 6.1 Torr preinfusion to 83.2 +/- 12.7 Torr (P less than 0.05). Tachyphylaxis to methacholine developed, requiring increases in infusion rates to maintain elevated RL. Abnormalities in lung function resolved promptly upon termination of the infusion. Two similarly instrumented control animals ventilated for 19 and 25 h without metacholine infusion had no change in RL, Cdyn, or PaO2. Histological examination of the lungs revealed no differences between infused and control animals. In spite of marked increases in RL, prolonged cholinergic stimulation produced only mild changes in gas exchange and no sustained changes in lung function or structure.


1994 ◽  
Vol 77 (1) ◽  
pp. 147-151 ◽  
Author(s):  
I. A. Dreshaj ◽  
R. J. Martin ◽  
M. J. Miller ◽  
M. A. Haxhiu

The tachykinin peptides substance P (SP) and neurokinin A (NKA) have been shown to induce tracheal smooth muscle contraction in piglets, and the enzyme neutral endopeptidase has been shown to modulate this effect. In these studies, we compared the SP and NKA responsiveness of piglet airways and lung parenchymal tissues in anesthetized paralyzed open-chest piglets 2–3 wk old, partitioning total lung resistance (RL) into airway resistance (Raw) and tissue resistance (Rti). During tidal breathing, pressure was measured at the trachea and in two alveolar regions by means of alveolar capsules. Intravenous administration of SP caused concentration-dependent increases in Rti and Raw and a decrease in dynamic lung compliance. Under baseline conditions, Rti contributed 74.6 +/- 1.9% (SE) of RL, and at any level of constriction, Rti accounted for > 50% of RL. The responses of Rti and Raw to NKA were negligible and were always significantly weaker than those to SP. These results indicate that both central airways and tissue contractile elements respond vigorously to SP, but not to NKA, in maturing piglets.


2003 ◽  
Vol 99 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Zen'ichiro Wajima ◽  
Toshiya Shiga ◽  
Tatsusuke Yoshikawa ◽  
Akira Ogura ◽  
Kazuyuki Imanaga ◽  
...  

Background After induction of anesthesia, lung resistance increases. The authors hypothesized that prophylactic bronchodilator treatment with intravenous colforsin daropate, a water-soluble forskolin derivative, before tracheal intubation would result in decreased lung resistance and increased lung compliance after tracheal intubation when compared with placebo medication. Methods Forty-six adult patients were randomized to placebo or colforsin daropate treatment. Patients in the control group received normal saline; patients in the colforsin group received 0.75 microg. kg-1 x min-1 colforsin daropate intravenously until the study ended. Thirty minutes after the study began, the authors administered 5 mg/kg thiamylal and 5 microg/kg fentanyl for induction of general anesthesia and 0.3 mg/kg vecuronium for muscle relaxation. A 15-mg. kg-1. h-1 continuous infusion of thiamylal followed anesthetic induction. Four, 8, 12, and 16 min after tracheal intubation, mean airway resistance (R(awm)), expiratory airway resistance (R(awe)), and dynamic lung compliance (C(dyn)) were measured. Results Patients in the colforsin group had significantly lower R(awm) and R(awe) and higher C(dyn) after intubation than those in the control group. Differences in R(awm), R(awe), and C(dyn) between the two groups persisted through the final measurement at 16 min. At 4 min after intubation, smokers had a higher R(awm) and a lower C(dyn) than nonsmokers in the control group. After treatment by intravenous colforsin daropate, R(awm), R(awe), and C(dyn) values were similar for smokers and nonsmokers after tracheal intubation. Conclusions Prophylactic treatment with colforsin daropate produced lower R(awm) and R(awe) and higher C(dyn) after tracheal intubation when compared with placebo medication. Pretreatment before intubation may be beneficial and advantageous for middle-aged smokers.


2003 ◽  
Vol 177 (1) ◽  
pp. R1-R4 ◽  
Author(s):  
J Zhou ◽  
ZM Kang ◽  
QM Xie ◽  
C Liu ◽  
SJ Lou ◽  
...  

Glucocorticoids (GCs) are routinely believed to work solely through genomic mechanisms. Recent evidence indicates that GCs can act at the membrane to exert rapid nongenomic effects on various tissues and cells. To ascertain whether nongenomic effects of GCs exist on the allergic asthma reaction, Hartley guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received inhaled budesonide (3 mg/ml suspended in Hydroxypropyl methylcellulose vehicle) for 5 minutes before ovalbumin challenge; Other animals received saline or blank vehicle as control. We measured the changes of lung resistance and dynamic lung compliance, the pulmonary function used to evaluate allergic asthma severity. Inhaled budesonide inhibited allergic reaction within 10 minutes, which would preclude genomic-mediated responses that normally takes several hours to occur. This study infers for the first time that rapid nongenomic effect of GCs exists on allergic asthma reaction, and provides a new way to investigate nongenomic mechanism of GCs. Further study would raise the possibility of new therapeutic strategies for allergic disease including asthma.


PLoS ONE ◽  
2008 ◽  
Vol 3 (2) ◽  
pp. e1575 ◽  
Author(s):  
Cordula Koerner-Rettberg ◽  
Sandra Doths ◽  
Anke Stroet ◽  
Jürgen Schwarze

2012 ◽  
Vol 302 (10) ◽  
pp. L1037-L1043 ◽  
Author(s):  
Madan M. Godbole ◽  
Geeta Rao ◽  
B. N. Paul ◽  
Vishwa Mohan ◽  
Preeti Singh ◽  
...  

Maternal hypothyroidism affects postnatal lung structure. High prevalence of hypothyroxinemia (low T4, normal T3) in iodine-deficient pregnant women and associated risk for neuropsychological development along with high infant/neonatal mortality ascribed to respiratory distress prompted us to study the effects of maternal hypothyroxinemia on postnatal lung development. Female Sprague Dawley rats were given a low-iodine diet (LID) with 1% KClO4in drinking water for 10 days, to minimize thyroid hormone differences. Half of these rats were continued on iodine-deficient diet; ID (LID with 0.005% KClO4) for 3 mo, whereas the rest were switched to an iodine-sufficient diet; IS [LID + potassium iodide (10 μg iodine/20 g of diet + normal drinking water)]. Pups born to ID mothers were compared with age-matched pups from IS mothers at postnatal days 8 (P8) and 16 (P16) ( n = 6–8/group). ID pups had normal circulating T3 but significantly low T4 levels ( P < 0.05) and concomitantly approximately sixfold higher thyroid hormone receptor-β mRNA in alveolar epithelium. Lung histology revealed larger and irregularly shaped alveoli in ID pups relative to controls. Lung function was assessed at P16 using a double-chambered plethysmograph and observed reduced tidal volume, peak inspiratory and expiratory flow, and dynamic lung compliance in ID pups compared with IS pups. Significant lowering of surfactant protein (SP)-B and SP-C mRNA and protein found in ID pups at P16. ID pups had 16-fold lower matrix metalloproteinase-9 mRNA levels in their alveolar epithelium. In addition, mRNA levels of thyroid transcription factor-1 and SP-D were significantly higher (3-fold) compared with IS pups. At P16, significantly lower levels of SP-B and SP-C found in ID pups may be responsible for immature lung development and reduced lung compliance. Our data suggest that maternal hypothyroxinemia may result in the development of immature lungs that, through respiratory distress, could contribute to the observed high infant mortality in ID neonates.


2014 ◽  
Vol 92 (5) ◽  
pp. 397-405 ◽  
Author(s):  
Shih-Ming Chen ◽  
Yau-Sheng Tsai ◽  
Su-Wen Lee ◽  
Ya-Hui Liu ◽  
Shuen-Kuei Liao ◽  
...  

Astragalus membranaceus, a traditional Chinese herb, has been used to improve airway inflammation and asthma. The present study investigated whether A. membranaceus has immunotherapeutic effects on asthma, a chronic inflammatory mucosal disease that is associated with excess production of IgE, eosinophilia, T helper 2 (Th2) cytokines, and bronchial hyperresponsiveness. An ovalbumin (OVA)-induced, chronic inflammatory airway murine asthma model was used to examine the status of pulmonary inflammation after the administration of A. membranaceus. The IgE levels in serum and bronchoalveolar lavage fluid showed a tendency to decrease after the administration of A. membranaceus. The number of eosinophils decreased and infiltration of inflammatory cells and collagen deposition declined in lung sections after A. membranaceus administration. The RNA and protein levels of Th2 cytokines and the ratio of the GATA3/T-bet mRNA levels decreased after A. membranaceus treatment. Furthermore, the mRNA level of peroxisome proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor, increased in the lung tissues of A. membranaceus–treated mice. Finally, an A. membranaceus water extract activated PPARγ activity in either human embryonic kidney 293 (HEK293) or A549 cells in a PPARγ-responsive element-containing luciferase reporter assay. These results indicate that A. membranaceus has an inhibitory effect on airway inflammation in a murine model of asthma through modulating the imbalanced relationship between Th1 and Th2 cytokines.


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