scholarly journals Effects of inhaled aminophylline on airway constriction and inflammation in ovalbumin-sensitized guinea pigs

Drug Delivery ◽  
2013 ◽  
Vol 21 (5) ◽  
pp. 321-327 ◽  
Author(s):  
Masato Muraki ◽  
Shota Wada ◽  
Takeshi Ohno ◽  
Souichirou Hanada ◽  
Hirochiyo Sawaguchi ◽  
...  
2009 ◽  
Vol 106 (4) ◽  
pp. 1257-1263 ◽  
Author(s):  
Neil R. Gleason ◽  
George Gallos ◽  
Yi Zhang ◽  
Charles W. Emala

GABAA channels are ubiquitously expressed on neuronal cells and act via an inward chloride current to hyperpolarize the cell membrane of mature neurons. Expression and function of GABAA channels on airway smooth muscle cells has been demonstrated in vitro. Airway smooth muscle cell membrane hyperpolarization contributes to relaxation. We hypothesized that muscimol, a selective GABAA agonist, could act on endogenous GABAA channels expressed on airway smooth muscle to attenuate induced increases in airway pressures in anesthetized guinea pigs in vivo. In an effort to localize muscimol's effect to GABAA channels expressed on airway smooth muscle, we pretreated guinea pigs with a selective GABAA antagonist (gabazine) or eliminated lung neural control from central parasympathetic, sympathetic, and nonadrenergic, noncholinergic (NANC) nerves before muscimol treatment. Pretreatment with intravenous muscimol alone attenuated intravenous histamine-, intravenous acetylcholine-, or vagal nerve-stimulated increases in peak pulmonary inflation pressure. Pretreatment with the GABAA antagonist gabazine blocked muscimol's effect. After the elimination of neural input to airway tone by central parasympathetic nerves, peripheral sympathetic nerves, and NANC nerves, intravenous muscimol retained its ability to block intravenous acetylcholine-induced increases in peak pulmonary inflation pressures. These findings demonstrate that the GABAA agonist muscimol acting specifically via GABAA channel activation attenuates airway constriction independently of neural contributions. These findings suggest that therapeutics directed at the airway smooth muscle GABAA channel may be a novel therapy for airway constriction following airway irritation and possibly more broadly in diseases such as asthma and chronic obstructive pulmonary disease.


2001 ◽  
Vol 21 (3) ◽  
pp. 151-157
Author(s):  
Y.-L. Lai ◽  
S.-C. Lee ◽  
L.-C. Lai ◽  
F.-C. Hu ◽  
T.-L. Tsai ◽  
...  

1993 ◽  
Vol 61 ◽  
pp. 229
Author(s):  
Chikashi Saitoh ◽  
Junko Maehara ◽  
Jun Ishikawa ◽  
Masaharu Asano

Neuropeptides ◽  
1992 ◽  
Vol 22 (1) ◽  
pp. 24 ◽  
Author(s):  
T. Fujii ◽  
M. Murai ◽  
H. Morimoto ◽  
D. Hagiwara ◽  
H. Miyake ◽  
...  

2000 ◽  
Vol 88 (3) ◽  
pp. 939-943 ◽  
Author(s):  
Y.-L. Lai ◽  
H.-C. Chou

Mice have been widely used in immunologic and other research to study the influence of different diseases on the lungs. However, the respiratory mechanical properties of the mouse are not clear. This study extended the methodology of measuring respiratory mechanics of anesthetized rats and guinea pigs and applied it to the mouse. First, we performed static pressure-volume and maximal expiratory flow-volume curves in 10 anesthetized paralyzed C57BL/6 mice. Second, in 10 mice, we measured dynamic respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow before and after methacholine challenge. Averaged total lung capacity and functional residual capacity were 1.05 ± 0.04 and 0.25 ± 0.01 ml, respectively, in 20 mice weighing 22.2 ± 0.4 g. The chest wall was very compliant. In terms of vital capacity (VC) per second, maximal expiratory flow values were 13.5, 8.0, and 2.8 VC/s at 75, 50, and 25% VC, respectively. Maximal flow-static pressure curves were relatively linear up to pressure equal to 9 cmH2O. In addition, methacholine challenge caused significant decreases in respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow, indicating marked airway constriction. We conclude that respiratory mechanical parameters of mice (after normalization with body weight) are similar to those of guinea pigs and rats and that forced expiratory maneuver is a useful technique to detect airway constriction in this species.


1984 ◽  
Vol 56 (6) ◽  
pp. 1666-1669 ◽  
Author(s):  
S. A. Silbaugh ◽  
J. L. Mauderly

Tidal volume measured by the barometric method is very sensitive to increases in compression and expansion of alveolar gas, such as would be expected to occur during airway narrowing or closure. By comparing a barometric method tidal volume signal (VT′) with a reference tidal volume (VT) obtained with a head-out pressure plethysmograph, a simple index related to gas compressibility effects was calculated (VT/VT′). Changes in this index were compared with decreases in dynamic compliance (Cdyn) during histamine aerosol challenge of 15 Charles River Hartley guinea pigs. Decreases in VT/VT′ occurred during all aerosol challenges and were correlated with decreases in Cdyn (r = 0.84, P less than 0.001). Decreases in VT/VT′ were most marked at Cdyn values of less than 50% of base line. At Cdyn of less than 15% of base line, VT′ was 3.1–4.8 times the VT reference signal. No increase in total pulmonary resistance was noted, and Cdyn and VT/VT′ returned to base line after histamine exposure was stopped. We conclude that gas compressibility effects become substantial during histamine-induced airway constriction in the guinea pig and that the VT/VT′ ratio appears to provide a simple noninvasive method of detecting these changes.


Sign in / Sign up

Export Citation Format

Share Document