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Department of Geriatrics, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Nagase, Takahide, Hirotoshi Matsui, Tomoko Aoki, Yasuyoshi
Ouchi, and Yoshinosuke Fukuchi. Lung tissue behavior in the mouse
during constriction induced by methacholine and endothelin-1. J. Appl. Physiol. 81(6):
2373-2378, 1996.
Recently, mice have been extensively used to
investigate the pathogenesis of pulmonary disease because appropriate
murine models, including transgenic mice, are being increasingly
developed. However, little information about the lung mechanics of mice
is currently available. We questioned whether lung tissue behavior and
the coupling between dissipative and elastic processes, hysteresivity
(
), in mice would be different from those in the other species. To
address this question, we investigated whether tissue resistance (Rti)
and in mice would be affected by varying lung volume, constriction
induced by methacholine (MCh) and endothelin-1 (ET-1), and
high-lung-volume challenge during induced constriction. From measured
tracheal flow and tracheal and alveolar pressures in open-chest ICR
mice during mechanical ventilation [tidal volume = 8 ml/kg,
frequency (f) = 2.5 Hz], we calculated lung resistance
(RL), Rti, airway resistance
(Raw), lung elastance (EL),
and (=
2
fRti/EL). Under
baseline conditions, increasing levels of end-expiratory transpulmonary
pressure decreased Raw and increased Rti. The administration of
aerosolized MCh and intravenous ET-1 increased
RL, Rti, Raw, and
EL in a dose-dependent manner.
Rti increased from 0.207 ± 0.010 to 0.570 ± 0.058 cmH2O · ml
1 · s
after 107 mol/kg ET-1
(P < 0.01). After induced
constriction, increasing end-expiratory transpulmonary pressure
decreased Raw. However, was not affected by changing lung volume,
constriction induced by MCh and ET-1, or high-lung-volume challenge
during induced constriction. These observations suggest that
1) is stable in mice regardless
of various conditions, 2) Rti is an
important fraction of RL and
increases after induced constriction, and
3) mechanical interdependence may
affect airway smooth muscle shortening in this species. In mammalian
species, including mice, analysis of may indicate that both Rti and
EL essentially respond to a
similar degree.
hysteresivity; airway resistance; tissue resistance; interdependence
INTRODUCTION IT HAS RECENTLY BEEN SHOWN in a number of mammalian
species that much of the resistive pressure drop across the lung occurs at the level of the lung tissues (9, 12-14, 20-25,
27). Furthermore, much of the increase in lung resistance
(RL) after induced
constriction is attributable to altered tissue resistance (Rti) (9,
12-14, 20-25, 27). The lung tissues can affect the magnitude
of bronchoconstriction through the airway-parenchymal interdependent
mechanism (15, 17). The parenchymal attachments to the airway walls may
act as an impedance to airway smooth muscle shortening (4, 15, 22-24, 29). Recently, it has been demonstrated in various species other than mice that the coupling between dissipative and elastic processes, which is defined as hysterisivity ( Recently, mice have been extensively used to investigate the
pathogenesis of pulmonary disease because appropriate murine models,
including transgenic mice, are being increasingly developed. Regarding
the lung mechanics of mice, however, little information is currently
available. We questioned whether airway and lung tissue behavior,
including To address this question, we measured airway resistance (Raw), Rti, and
MATERIALS AND METHODS Animal Preparation
), is fairly stable regardless of various challenge (6).
, in the mouse would be different from that in other
species.
in mice by using the alveolar capsule technique (5). In the present
study, we investigated whether Rti and in mice would be affected by
1) varying frequencies and tidal volumes, 2) varying lung volume,
3) constriction induced by different agonists [i.e., methacholine (MCh) and endothelin-1
(ET-1)], and 4)
high-lung-volume challenge during induced constriction.
The alveolar capsules were made out of 1-ml plastic syringes. One or two alveolar capsules were affixed to the pleural surface of the anterior portion of lungs with cyanoacrylate. The pleura underneath the capsule was punctured with an electrocautery needle through the central port of the capsule (depth <1 mm) to bring the underlying alveoli into communication with the capsule chamber. A piezoresistive microtransducer (model 8507C-2, Endevco, San Juan Capistrano, CA) was placed in the port of the capsule to measure alveolar pressure (PA). Tracheal pressure (Ptr) was also measured by a piezoresistive microtransducer (model 8510B-2, Endevco) placed in a lateral port of the tracheal cannula. Tracheal flow was measured by means of a Fleisch pneumotachograph (no. 00000). Volume (V) was calculated by digital integration of the flow signal. All signals were amplified, filtered at a cutoff frequency of 100 Hz, and converted from analog to digital by a 12-bit analog-to-digital converter (model DT2801-A, Data Translation, Marlborough, MA). The signals were sampled at a rate of 200 Hz and stored on an IBM-AT-compatible computer.
Calculation of Resistance and
|
Rti was calculated by fitting the equation of motion to PA
|
are constants, the values of
which were also estimated by multiple linear regression. The values of
RL and Rti were accepted only
when the values of EL obtained
from Ptr and PA were different
by <10% and both K and
K were <1
cmH2O different from the real
value of end-expiratory transpulmonary pressure (Ptp).
Raw was calculated by subtraction
|
(a structural damping coefficient) was
calculated as follows
|
Protocol
Effects of varying frequencies and tidal volumes. To examine frequency and tidal volume dependences of resistance and, we made measurements of 30-s duration at each frequency (0.313, 0.625, 1.25, and 2.5 Hz) and at each tidal volume (5, 10, and 20 ml/kg;
n = 5). Frequencies and tidal volumes
were changed in random order.
Effects of varying Ptp under baseline conditions.
Baseline measurements were obtained 1 min after two deep
inflations (peak Ptr of 30 cmH2O)
were performed to standardize volume history.
Measurements of 10-s duration were made at each level of Ptp (3, 5, 7, 9, and 11 cmH2O) and at each
frequency (0.313, 0.625, 1.25, and 2.5 Hz;
n = 5, 5, 5, and 11, respectively).
Ptp was altered in ascending order.
Effects of MCh administration.
In seven mice, inhalations of saline and MCh were administered at Ptp
of 3 cmH2O. Aerosols were
generated by an ultrasonic nebulizer (Ultra-Neb100, DeVilbiss,
Somerset, PA), which produces particles with a mean aerodynamic
diameter of 4.8 µm. Aerosols were delivered into the trachea for 30 s, and the aerosols of MCh were administered in a dose-response manner
(0.01, 0.1, 1, 10, and 100 mg/ml).
Effects of ET-1 administration.
Synthetic ET-1 (Peptide Institute, Osaka, Japan) was dissolved in
phosphate-buffered saline (PBS) at concentrations of
109-107
mol/kg. After two deep inflations (peak Ptr of 30 cmH2O) were performed twice to
standardize volume history, baseline measurements of 10-s duration were
sampled during tidal ventilation. After baseline
measurements, 0.1 ml of PBS and ET-1 solutions was given intravenously
in a half-log increasing manner in five mice. Each dose of ET-1 was
administered 5 min after the previous dose to obtain a cumulative
concentration-response curve.
Effects of varying Ptp during induced constriction.
One minute after the administration of 100 mg/ml MCh
aerosol or 107 mol/kg ET-1
(iv), measurements of 10-s duration were obtained at two different
levels of Ptp (3 and 11 cmH2O) in
ascending order. These measurements were completed within 1 min, and
preliminary experiments showed that the magnitude of
bronchoconstriction remained unchanged during this period.
Statistical Analysis
Statistical significances were examined with analysis of variance (Fisher's least significant difference test). P values <0.05 were taken as significant. Data are expressed as means ± SE.RESULTS
Effects of Varying Frequencies and Tidal Volumes
The effects of different frequencies and tidal volumes are shown in Fig. 1. Rti had a negative dependence on frequency and a slight positive dependence on tidal volume. In contrast, had a positive dependence on frequency and a slight
negative dependence on tidal volume.
;
B) in mice.
n, No. of measurements.
* P < 0.05 vs. frequency = 2.5 Hz.
+ P < 0.05 vs. VT = 5 ml/kg.
Effects of Varying Ptp Under Baseline Conditions
Figure 2 summarizes the effects of changing Ptp on baseline RL, Rti, Raw, EL, and. Increasing Ptp
increased Rti and EL and decreased Raw significantly at Ptp 
5
cmH2O. The was not affected by
the changes in Ptp at each frequency.
(B) under baseline conditions in
mice. n, No. of measurements; f,
frequency. * P < 0.01 vs. Ptp = 3 cmH2O.
+ P < 0.01 vs. f = 2.5 Hz.
Effects of MCh Administration
MCh concentration-response curves for RL, Rti, Raw, EL, and are shown in Fig.
3. After 0.1 mg/ml of MCh, Rti and
EL significantly increased,
whereas Raw was increased at 10 mg/ml. Meanwhile, was not altered
by increasing dose of MCh.
(B) in mice.
n, No. of measurements; SAL, saline.
* P < 0.01 vs.
SAL.
Effects of ET-1 Administration
Figure 4 summarizes the responses to ET-1 in mice. RL, Rti, Raw, and EL significantly increased after 107.5 mol/kg ET-1
administration. Rti increased from 0.207 ± 0.010 to 0.570 ± 0.058 cmH2O · ml1 · s
after 107 mol/kg ET-1
(P < 0.01). The was not
significantly affected by increasing dose of ET-1.
(B) in mice.
n, No. of measurements. PBS,
phosphate-buffered saline. *P < 0.01 vs. PBS.
Effects of Varying Ptp During Induced Constriction
The effects of increased Ptp levels on Rti, Raw, and during MCh and ET-1 induced constriction are shown in Fig.
5. Increased Ptp levels significantly
decreased Raw (P < 0.01) and
increased Rti (P < 0.01), whereas
changing Ptp did not affect during MCh- and ET-1-induced
constriction.
(B) during MCh- and ET-1-induced
constriction. n, No. of measurements. * P < 0.01 vs. Ptp = 3 cmH2O.
DISCUSSION
The results of the present study show that is extremely stable in
mice in the physiological range of breathing. The was not affected
by changing lung volume, constriction induced by MCh and ET-1, and
high-lung-volume challenge during induced constriction. Rti is an
important fraction of RL and
increases after induced constriction in mice. Increasing lung volume
decreased Raw under the baseline conditions and during induced
constriction, suggesting that mechanical interdependence may affect
airway smooth muscle shortening in this species. These findings
indicate that airway and lung tissue behavior, including , in the
mouse would not be different from that in other species.
Before the results are discussed, technical issues warrant
consideration. It has been well described that lung mechanics, including resistance and elastance, depend on frequencies and tidal
volumes (6, 8). In the present study, we investigated whether lung
tissue behavior is affected by different frequencies and tidal volumes
under unconstricted state. On the other hand, we were able to study the
effects of agonist-induced constriction only at a single frequency (2.5 Hz) and tidal volume (8 ml/kg), which were presumably in the
physiological range of breathing of mice. As shown in Fig. 1, is
most meaningful at low frequencies, where it is insensitive to
frequency. However, we failed to obtain the data at low frequencies
during induced constriction because severe bradycardia or cardiac
arrest occurred during low-frequency ventilation. After agonist-induced
constriction, we therefore analyzed the data obtained at 2.5 Hz, where
is sensitive to changes in frequency.
The is the ratio of the energy dissipated per cycle to the stored
potential energy at maximum volume (6). As shown in Fig. 1, had a
positive dependence on frequency and a slight negative dependence on
tidal volume. Meanwhile, in the physiological range of breathing, was not significantly altered by different levels of Ptp, constriction
elicited by MCh and ET-1, and changes in lung volume during induced
constriction. These findings suggest that the coupling between
dissipative and elastic processes in mice may not be different from
that in any other larger mammalian species. In Table
1, the estimates of calculated from
previously reported data are summarized. In the
physiological range of breathing, the absolute values of are quite
similar in rats (21, 22), guinea pigs (20), and rabbits (25). In dogs,
Ludwig et al. (13) demonstrated that was 0.15 ± 0.02 during
low-frequency (0.05-Hz) tidal volume (10-12 ml/kg) ventilation and
that was significantly increased by constriction induced by
prostaglandin F2
, histamine,
and MCh but was not affected by deep inflation. Taken together, in
mammalian species from mice to dogs, analysis of may indicate that
both Rti and EL essentially
respond to a similar degree.
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In mice, Rti is a substantial fraction of
RL (40-60%) in the
physiological range of breathing, suggesting that the relative contributions of Rti and Raw to
RL are essentially similar in various mammalian species (9, 12, 14, 20-25, 27). One of the
possible mechanisms to explain this phenomenon is as follows. One might
assume that Raw follows Poisseuille's law; i.e., Raw is related to
L/r4,
where L is airway length and
r is airway caliber. If all linear dimensions scale as V2/3, then it
is expected that Raw would scale as 1/V. Rti is assumed to follow the structural damping law; i.e., Rti is related to EL. Because is roughly
constant and EL, the reciprocal
of the compliance, scales 1/V, Rti is expected to scale as
1/V. This theory suggests that both Raw and Rti are
dependent on animal size but that the ratio of Raw to Rti would be
constant. The results of the present study might support
this mechanism.
Under baseline conditions, increasing lung volume decreased Raw and increased Rti in mice, as has been previously described in other species. In dogs, it has been reported by Ludwig et al. (12), who partitioned pulmonary resistance into Raw and Rti with use of alveolar capsules, that lung inflation decreased Raw. In rats and guinea pigs, the effects of changing lung volume on Raw and Rti have also been reported, whereas the bronchodilating effect of lung volume is less in the guinea pig (24). In mice, Raw was reduced by 83% at Ptp of 11 cmH2O compared with Ptp of 3 cmH2O, which was a similar degree to that observed in rats (24).
After constriction induced by MCh and ET-1 in mice, increases in Rti were observed, as has been shown in several other animal species (9, 12-14, 20-25, 27). However, the mechanisms that give rise to increases in Rti are not clearly explained. Potential mechanisms include constriction of parenchymal contractile elements (10), changes in alveolar geometry and the behavior of the air-liquid interface (1, 3), and microatelectasis (6, 30, 31). In addition, changes in the conducting airways causing alterations in parenchymal stress and elasticity might be related to the observed increase in Rti (18). Meanwhile, Kimmel et al. (11) have made theoretical analysis and concluded that changes in Rti associated with parenchymal distortions are slight compared with those associated with volumetric expansion.
As expected, Raw increased after MCh- and ET-1-induced constriction in
mice. In mice, Raw significantly increased after the administration of
10 mg/ml MCh or 107.5
mol/kg ET-1. In guinea pigs, it has been shown that Raw significantly increased after 1 mg/ml MCh (23) or
109.5 mol/kg ET-1 (20),
suggesting that mice are more resistant to exogenous administration of
MCh and ET-1 than are guinea pigs. The mechanisms that may explain this
airway narrowing include smooth muscle contraction, airway wall
thickening, and intraluminal secretions (19, 26). Potential alterations
in airway compliance after induced constriction might also be involved
in the observed increases in Raw (28).
During constriction, increasing lung volume decreased Raw, suggesting that mechanical-interdependent forces might affect bronchoconstriction in this species. It has been reported in several species that airway-parenchymal interdependence affects the magnitude of bronchoconstriction. In humans, it has been demonstrated by Ding et al. (4) that the maximal RL after inhaled MCh decreases at higher lung volumes. In dogs, Ludwig et al. (13) have reported that Raw decreased at the higher lung volume during agonist-induced constriction, whereas it has been shown by Gunst and colleagues (7, 32) that airway closure during induced constriction in both in vitro and in vivo canine lungs could be reversed at higher Ptp values. In cats, it has been reported that increasing lung volume reduces the level of bronchoconstriction (29). In rats, Bellofiore et al. (2) have described that the response to MCh was enhanced in elastase-treated animal model of emphysema and have suggested that the increased response in RL was caused by loss of lung elastic recoil. In guinea pigs, it has been demonstrated that airway-parenchymal interdependence is important in determining the level of bronchoconstriction, whereas the lung volume dependence of Raw is less compared with that in rats (24). The present study suggests that the mechanical interdependence between airways and parenchymal lung tissues could modify the airway smooth muscle shortening as an impedance and affect the magnitude of bronchoconstriction in mice, one of the smallest mammalian species.
In summary, we demonstrated that was stable in mice in the
physiological range of breathing and was not affected by changing lung
volume, constriction induced by MCh and ET-1, and high-lung-volume challenge during induced constriction. Rti was an important fraction of
RL at baseline and increased
after exogenous constriction in mice. Increasing lung volume reduced
Raw during induced constriction, suggesting that mechanical
interdependence between airways and parenchymal tissues may modify
airway smooth muscle shortening in this species. These observations
might be useful to understand the pulmonary mechanics in the mouse and
provide an important step for the dynamic study of lung behavior in the
mouse, one of the most extensively used animal models.
ACKNOWLEDGEMENTS
The authors are thankful to Dr. E. Sudo and Y. Tateno for helpful assistance.
FOOTNOTES
Address for reprint requests: T. Nagase, Dept. of Geriatrics, Faculty of Medicine, Univ. of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
Received 7 March 1996; accepted in final form 2 August 1996.
REFERENCES
| 1. | Bachofen, H., S. Schürch, M. Urbinelli, and E. R. Weibel. Relations among alveolar surface tension, surface area, volume, and recoil pressure. J. Appl. Physiol. 62: 1878-1887, 1987. |
| 2. | Bellofiore, S., D. H. Eidelman, P. T. Macklem, and J. G. Martin. Effects of elastase-induced emphysema on airway responsiveness to methacholine in rats. J. Appl. Physiol. 66: 606-612, 1989. |
| 3. | Colebatch, H. J. H., C. R. Olsen, and J. A. Nadel. Effect of histamine, serotonine, and acetylcholine on the peripheral airways. J. Appl. Physiol. 21: 217-226, 1966. |
| 4. | Ding, D. J., J. G. Martin, and P. T. Macklem. Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans. J. Appl. Physiol. 62: 1324-1330, 1987. |
| 5. | Fredberg, J. J., D. H. Keefe, G. M. Glass, R. G. Castile, and I. D. Frantz III. Alveolar pressure nonhomogeneity during small-amplitude high-frequency oscillation. J. Appl. Physiol. 57: 788-800, 1984. |
| 6. | Fredberg, J. J., and D. Stamenovic. On the imperfect elasticity of lung tissue. J. Appl. Physiol. 67: 2408-2419, 1989. |
| 7. | Gunst, S. J., D. O. Warner, T. A. Wilson, and R. E. Hyatt. Parenchymal interdependence and airway response to methacholine in excised dog lobes. J. Appl. Physiol. 65: 2490-2497, 1988. |
| 8. | Hirai, T., M. Hosokawa, K. Kawakami, Y. Takubo, N. Sakai, Y. Oku, K. Chin, M. Ohi, K. Higuchi, K. Kuno, and M. Mishima. Age-related changes in the static and dynamic mechanical properties of mouse lungs. Respir. Physiol. 102: 195-203, 1995. |
| 9. | Ingenito, E. P., B. Davison, and J. J. Fredberg. Tissue resistance in the guinea pig at baseline and during methacholine constriction. J. Appl. Physiol. 75: 2541-2548, 1993. |
| 10. | Kapanci, Y., A. Assimacopoulos, C. Irle, A. Zwahlen, and G. Gabbiani. "Contractile interstitial cells" in pulmonary alveolar septa: a possible regulator of ventilation/perfusion ratio? J. Cell Biol. 60: 375-392, 1974. |
| 11. | Kimmel, E., M. Seri, and J. J. Fredberg. Lung tissue resistance and hysteretic moduli of lung parenchyma. J. Appl. Physiol. 79: 461-466, 1995. |
| 12. | Ludwig, M. S., I. Dreshaj, J. Solway, A. Munoz, and R. H. Ingram, Jr. Partitioning of pulmonary resistance during constriction in the dog: effects of volume history. J. Appl. Physiol. 62: 807-815, 1987. |
| 13. | Ludwig, M. S., F. M. Robatto, S. Simard, D. Stamenovic, and J. J. Fredberg. Lung tissue resistance during contractile stimulation: structural damping decomposition. J. Appl. Physiol. 72: 1332-1337, 1992. |
| 14. | Ludwig, M. S., P. V. Romero, and J. H. T. Bates. A comparison of the dose-response behavior of canine airways and parenchyma. J. Appl. Physiol. 67: 1220-1225, 1989. |
| 15. | Macklem, P. T. A theoretical analysis of the effect of airway smooth muscle load on airway narrowing. Am. J. Respir. Crit. Care Med. 153: 83-89, 1996. |
| 16. | Mead, J. Mechanical properties of lungs. Physiol. Rev. 41: 281-330, 1961. |
| 17. | Mead, J., T. Takishima, and D. Leith. Stress distribution in lungs: a model of pulmonary elasticity. J. Appl. Physiol. 28: 596-608, 1970. |
| 18. | Mitzner, W., S. Blosser, D. Yager, and E. Wagner. Effect of bronchial smooth muscle contraction on lung compliance. J. Appl. Physiol. 72: 158-167, 1992. |
| 19. | Moreno, R. H., J. C. Hogg, and P. D. Paré. Mechanics of airway narrowing. Am. Rev. Respir. Dis. 133: 1171-1180, 1986. |
| 20. | Nagase, T., Y. Fukuchi, H. Matsui, T. Aoki, T. Matsuse, and H. Orimo. In vivo effects of endothelin A- and B-receptor antagonists in guinea pigs. Am. J. Physiol. 268 (Lung Cell. Mol. Physiol. 12): L846-L850, 1995. |
| 21. | Nagase, T., Y. Fukuchi, T. Matsuse, E. Sudo, H. Matsui, and H. Orimo. Antagonism of ICAM-1 attenuates airway and tissue responses to antigen in sensitized rats. Am. J. Respir. Crit. Care Med. 151: 1244-1249, 1995. |
| 22. | Nagase, T., Y. Fukuchi, S. Teramoto, T. Matsuse, and H. Orimo. Mechanical interdependence in relation to age: effects of lung volume on airway resistance in rats. J. Appl. Physiol. 77: 1172-1177, 1994. |
| 23. | Nagase, T., T. Ito, M. Yanai, J. G. Martin, and M. S. Ludwig. Responsiveness of and interactions between airways and tissue in guinea pigs during induced constriction. J. Appl. Physiol. 74: 2848-2854, 1993. |
| 24. | Nagase, T., J. G. Martin, and M. S. Ludwig. Comparative study of mechanical interdependence: effect of lung volume on Raw during induced constriction. J. Appl. Physiol. 75: 2500-2505, 1993. |
| 25. | Nagase, T., H. Matsui, E. Sudo, T. Matsuse, M. S. Ludwig, and Y. Fukuchi. Effects of lung volume on airway resistance during induced constriction in papain-treated rabbits. J. Appl. Physiol. 80: 1872-1879, 1996. |
| 26. | Paré, P. D., B. R. Wiggs, A. James, J. C. Hogg, and C. Bosken. The comparative mechanics and morphology of airways in asthma and in chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 143: 1189-1193, 1991. |
| 27. | Romero, P. V., and M. S. Ludwig. Maximal methacholine-induced constriction in rabbit lungs: interactions between airways and tissues? J. Appl. Physiol. 70: 1044-1050, 1991. |
| 28. | Sasaki, H., and F. G. Hoppin, Jr. Hysteresis of contracted airway smooth muscle. J. Appl. Physiol. 47: 1251-1262, 1979. |
| 29. | Sly, P. D., K. A. Brown, J. H. T. Bates, P. T. Macklem, J. Milic-Emili, and J. G. Martin. Effect of lung volume on interrupter resistance in cats challenged with methacholine. J. Appl. Physiol. 64: 360-366, 1988. |
| 30. | Smaldone, G. C., W. Mitzner, and M. Itoh. Role of alveolar recruitment in lung inflation: influence on pressure-volume hysteresis. J. Appl. Physiol. 55: 1321-1332, 1983. |
| 31. | Stamenovic, D., and T. A. Wilson. Parenchymal stability. J. Appl. Physiol. 73: 596-602, 1992. |
| 32. | Warner, D. O., and S. J. Gunst. Limitation of maximal bronchoconstriction in living dogs. Am. Rev. Respir. Dis. 145: 553-560, 1992. |
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R. F. M. Gomes, F. Shardonofsky, D. H. Eidelman, and J. H. T. Bates Respiratory mechanics and lung development in the rat from early age to adulthood J Appl Physiol, May 1, 2001; 90(5): 1631 - 1638. [Abstract] [Full Text] [PDF]
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D. S. Faffe, G. H. Silva, P. M. P. Kurtz, E. M. Negri, V. L. Capelozzi, P. R. M. Rocco, and W. A. Zin Lung tissue mechanics and extracellular matrix composition in a murine model of silicosis J Appl Physiol, April 1, 2001; 90(4): 1400 - 1406. [Abstract] [Full Text] [PDF]
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R. F. M. Gomes, X. Shen, R. Ramchandani, R. S. Tepper, and J. H. T. Bates Comparative respiratory system mechanics in rodents J Appl Physiol, September 1, 2000; 89(3): 908 - 916. [Abstract] [Full Text] [PDF]
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T. Nagase, H. Kurihara, Y. Kurihara, T. Aoki-Nagase, R. Nagai, and Y. Ouchi Disruption of ET-1 gene enhances pulmonary responses to methacholine via functional mechanism in knockout mice J Appl Physiol, December 1, 1999; 87(6): 2020 - 2024. [Abstract] [Full Text] [PDF]
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T. NAGASE, S. ISHII, H. KATAYAMA, Y. FUKUCHI, Y. OUCHI, and T. SHIMIZU Airway Responsiveness in Transgenic Mice Overexpressing Platelet-activating Factor Receptor . Roles of Thromboxanes and Leukotrienes Am. J. Respir. Crit. Care Med., November 1, 1997; 156(5): 1621 - 1627. [Abstract] [Full Text]
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T. NAGASE, H. KURIHARA, Y. KURIHARA, T. AOKI, Y. FUKUCHI, Y. YAZAKI, and Y. OUCHI Airway Hyperresponsiveness to Methacholine in Mutant Mice Deficient in Endothelin-1 Am. J. Respir. Crit. Care Med., February 1, 1997; 157(2): 560 - 564. [Abstract] [Full Text]
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