| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Vol. 84, Issue 4, 1431-1436, April 1998
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612
 |
ABSTRACT |
|---|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
The purpose of this study was to determine whether an aqueous extract of grain sorghum dust increases macromolecular efflux from the nasal mucosa in vivo and, if so, whether this response is mediated, in part, by substance P. Suffusion of grain sorghum dust extract on the in situ nasal mucosa of anesthetized hamsters elicits a significant increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass, 70 kDa; P < 0.05). This response is significantly attenuated by CP-96345 and RP-67580, two selective, but structurally distinct, nonpeptide neurokinin 1 (substance P)-receptor antagonists, but not by CP-96344, the 2R,3R enantiomer of CP-96345 (P < 0.05). CP-96345 has no significant effects on adenosine-induced increase in clearance of FITC-dextran from the in situ nasal mucosa. CP-96345 and RP-67580, but not CP-96344, significantly attenuate substance P-induced increases in clearance of FITC-dextran from the in situ nasal mucosa (P < 0.05). Collectively, these data suggest that grain sorghum dust elicits neurogenic plasma exudation from the in situ nasal mucosa.
microcirculation; neurogenic inflammation; rhinitis; tachykinins; neurokinin 1-receptor antagonist; adenosine; hamster
| |
INTRODUCTION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
IT IS ESTIMATED that more than 2.5 million people in the US are exposed to grain dust on a regular basis (3, 15, 28). A relatively large number of these individuals experience incapacitating symptoms of nasal irritation consisting of nasal congestion, rhinorrhea, and postnasal drip (4, 5, 15, 21). Hence, the economic impact this ailment may have on the farming industry is substantial, consisting of lost productivity, days out of work, and increased medical expense (3, 28). However, the mechanisms underlying nasal mucosal irritation in individuals exposed to grain dust are uncertain.
We reasoned that, because grain dust particles are deposited primarily on the nasal mucosa (3-5, 15, 21, 28) and because the nasal mucosa is densely innervated by sensory nerves (13, 14, 20, 27), one potential mechanism whereby grain dust could elicit nasal mucosa irritation is by stimulating these nerves to release tachykinins, the best known of which is substance P (1, 2, 6, 7, 10, 11, 13, 20, 27). On its release, substance P elicits neurogenic inflammation, a characteristic feature of which is plasma exudation from microvessels, leading to interstitial edema, nasal congestion, and tissue dysfunction (1, 7, 10, 11, 13, 20, 27, 29).
The purpose of this study was to begin to address this issue by determining whether an aqueous extract of grain sorghum dust (GDE), a prevalent environmental toxicant in the farming industry (3, 4, 11, 28, 31, 32), increases macromolecular efflux from the in situ nasal mucosa of hamsters and, if so, whether this response is mediated, in part, by substance P.
| |
METHODS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Collection and Preparation of GDE
Settled dust from sorghum grains was collected from storage bins during the harvest season (11, 31, 32). An aqueous extract of the dust was prepared as previously described in our laboratory (11, 31, 32). Briefly, 1 g of grain sorghum dust was gently mixed with 10 ml of Hanks' balanced salt solution for 60 min. The suspension was allowed to settle at room temperature for 90 min. Large-particulate debris were removed from the suspension by centrifugation at 5,000 g for 10 min. The supernatant was decanted and filtered through a 0.22-µm-pore filter (Millipore, Bedford, MA). Samples of the supernatant, designated arbitrarily as 100% GDE (4, 9, 31, 32), were snap frozen in liquid nitrogen and stored at
70°C until used.
Preparation of Animals
Adult male hamsters weighing 125 ± 2 g (n = 58) were anesthetized with pentobarbital sodium (6 mg/100 g body wt ip). A tracheotomy was performed to facilitate spontaneous breathing. A femoral vein was cannulated to inject the intravascular tracer, fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass, 70 kDa; 40 mg/100 g body wt dissolved in 1.0 ml saline and administered over 1 min) and supplemental anesthesia (2-4 mg · 100 g body wt
1 · h1).
A femoral artery was cannulated to record arterial blood pressure and
to obtain blood samples. Body temperature was kept constant (37-38°C) throughout the experiment by using a heating pad.
The left nostril was prepared for experimentation by using a method recently described by our laboratory (8). A polyethylene tubing (PE-10; Clay Adams, Parsippany, NJ) was introduced ~3 mm into the left nostril along the nasal septum. The tongue was extruded from the mouth with forceps and secured to a pedestal by using a silk thread (4-0; Look, Norwell, MA). A polyethylene tube (PE-90) was then introduced through the mouth into the left posterior concha under direct observation. The left nostril was covered with a laboratory film (PARAFILM "M," American National Can, Greenwich, CT) to prevent leakage of suffusate. The anterior nasal cannula was connected via a three-way valve to a reservoir containing warmed bicarbonate buffer (37-38°C) composed of (in mM) 131.9 NaCl, 2.95 KCl, 1.48 CaCl2, 0.76 MgCl2, and 11.87 NaHCO3, which allowed continuous suffusion of the left nasal cavity. The cannula was also connected to an infusion pump (model 341B, Sage Instruments, Boston, MA) for continuous administration of GDE and drugs into the suffusate. The posterior nasal cannula was connected through a peristaltic pump (Cole-Parmer Instrument, Chicago, IL) to a fraction collector (Cygnet, ISCO, Lincoln, NE). The flow rate was adjusted such that the entire suffusate introduced through the anterior nasal cannula was collected into the fraction collector.
Determination of Clearance of Macromolecules
The suffusate was collected at 5-min intervals into glass test tubes throughout the experiment (8). The concentration of FITC-dextran was determined in all samples. Arterial blood samples were collected in heparinized capillary tubes (70-µl volume; Scientific Products, McGaw Park, IL) beginning 5 min before and 5, 60, 150, and 240 min after injection of FITC-dextran. The concentration of FITC-dextran was determined in all plasma samples and remained constant throughout the duration of the experiment, consistent with the study by Mayhan and Joyner (23), thereby obviating the need to collect 10 additional arterial blood samples during the first 60 min of experimentation.To quantitate the concentration of FITC-dextran in plasma and suffusate, a standard curve for FITC-dextran concentrations vs. percent emission was performed on a spectrophotofluorometer (Photon Technology International, Princeton, NJ). The standard was FITC-dextran, which was prepared on a weight per volume basis. With bicarbonate buffer used as background, a standard curve was generated for each experiment, and each curve was subjected to linear regression analysis. The percent emission for unknown samples (plasma and suffusate) was measured on the spectrophotofluorometer, and the concentration of FITC-dextran was calculated from the standard curve. In preliminary studies, minimal fluorescence signal (<2% above background) was detected when drugs were added to the buffer and when plasma and suffusate samples were examined before FITC-dextran was added. Clearance of FITC-dextran was determined by calculating the ratio of suffusate (ng/ml) to plasma (mg/ml) concentration of FITC-dextran and multiplying this ratio by the suffusate flow rate (ml/min).
Experimental Protocols
A schematic representation of the experimental design is shown in Fig. 1.
|
Effects of neurokinin 1 (NK1 )-receptor antagonists on GDE-induced increase in macromolecular efflux. The purpose of these studies was to determine whether GDE increases macromolecular efflux from the in situ hamster nasal mucosa and, if so, whether NK1-receptor antagonists attenuate this response. After bicarbonate buffer was suffused into the left nostril for 15 min, FITC-dextran was injected intravenously and the suffusate was collected for 40 min (equilibration period). Then, two concentrations of GDE (1 and 10%) were suffused into the left nostril for 20 min in an arbitrary order. At least 60 min elapsed between subsequent suffusions of GDE. Thereafter, CP-96345 (5 mg/kg) or RP-67580 (1 mg/kg) was administered intravenously over 30 min by using an infusion pump, and suffusion of GDE was repeated. In another group of animals, GDE (10%) was suffused into the left nostril for 20 min before and 30 min after intravenous administration of CP-96344 (5 mg/kg), the 2R,3R enantiomer of CP-96345. Clearance of FITC-dextran was determined 5 min before each intervention, every 5 min for 60 min during each intervention, and 150 and 240 min after intravenous injection of FITC-dextran. In preliminary studies, we determined that repeated suffusions of GDE (1 and 10%) were associated with reproducible results. The concentrations of GDE used in these studies are based on a previous study in our laboratory and reports in the literature (4, 11, 31, 32).
Specificity of NK1-receptor-antagonist-induced responses. The purpose of these studies was to determine the specificity of CP-96345 attenuation of GDE-induced increase in macromolecular efflux from the in situ hamster nasal mucosa. We used two strategies to accomplish this goal. In one group of animals, we determined whether CP-96345 attenuates adenosine-induced increase in macromolecular efflux from the in situ hamster nasal mucosa. Adenosine, like substance P, increases clearance of macromolecules from the hamster microcirculation in a receptor-dependent fashion (8-11, 12, 26). After the equilibration period, FITC-dextran was injected intravenously, and the suffusate was collected for 40 min. Then, adenosine (10 µM) was suffused into the left nostril for 5 min. Forty-five minutes later, CP-96345 (5 mg/kg) was infused intravenously for 30 min, and suffusion of adenosine was repeated.
In a second series of experiments, we determined whether NK1-receptor antagonists attenuate substance P-induced increase in macromolecular efflux from the in situ hamster nasal mucosa. After the equilibration period, FITC-dextran was injected intravenously and the suffusate was collected for 40 min. Then, two concentrations of substance P (1 and 10 µM) were suffused into the left nostril for 5 min in an arbitrary order. At least 45 min elapsed between subsequent suffusions of substance P. Thereafter, CP-96345 (5 mg/kg) or RP-67580 (1 mg/kg), two selective, but structurally distinct, NK1-receptor antagonists (1, 7, 10, 11), was infused intravenously over 30 min by using an infusion pump, and suffusion of substance P was repeated. In another group of animals, substance P (1 µM) was suffused for 5 min before and after intravenous administration of CP-96344 (5 mg/kg) for 30 min. Clearance of FITC-dextran was determined during each intervention as outlined above. In preliminary studies, we determined that repeated suffusions of adenosine (10 µM) and substance P (1 and 10 µM) were associated with reproducible results. In addition, suffusion of saline (vehicle) on the nasal mucosa for the entire duration of the experiment and intravenous infusion of CP-96345 (5 mg/kg) and RP-67580 (1 mg/kg) alone for 30 min had no significant effects on clearance of FITC-dextran. The concentrations of adenosine, substance P, CP-96345, RP-67580, and CP-96344 used in these studies are based on previous and preliminary studies in our laboratory and reports in the literature (1, 7-12, 26).Drugs
FITC-dextran and adenosine were obtained from Sigma Chemical (St. Louis, MO). Hanks' balanced salt solution was obtained from GIBCO BRL (Grand Island, NY). CP-96345 and CP-96344 were gifts from Pfizer (New York, NY). RP-67580 was a gift from Rhône-Poulenc Rorer (Vitry sur Seine, France). All drugs were prepared on the day of the experiment and diluted in saline to the desired concentrations.Data and Statistical Analyses
When a test compound was suffused into the animal's nose, we determined the maximal change in clearance of FITC-dextran and used it as the response to that compound. Data are expressed as means ± SE. Statistical analysis was performed by using two-way analysis of variance and the Newman-Keuls test for multiple comparisons. The number of experiments is given as n, with each experiment representing a separate animal. P < 0.05 was considered significant.| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Mean arterial pressure was 97 ± 4 mmHg at the start and 93 ± 6 mmHg at the conclusion of the experiments (n = 58; P > 0.5).
Effects of NK1-Receptor Antagonists on GDE-Induced Increase in Macromolecular Efflux
Suffusion of GDE (1 and 10%) elicited a significant, concentration-dependent increase in clearance of FITC-dextran from the nasal mucosa (Fig. 2; each group, n = 4; P < 0.05). Maximal effect was observed within 30 min after the start of suffusion, and clearance of FITC-dextran returned to baseline 60 min after suffusion was stopped. CP-96345 and RP-67580 significantly attenuated GDE-induced responses (Fig. 2; each group, n = 4; P < 0.05). Clearance of FITC-dextran decreased from 63.3 ± 9.6 ml/min × 106 during suffusion of GDE
(10%) alone to 35.0 ± 6.9 ml/min × 106 during suffusion of GDE
(10%) in the presence of CP-96345 (5 mg/kg iv; Fig.
2A; each group,
n = 4;
P < 0.05). Clearance of FITC-dextran
decreased from 63.3 ± 9.6 ml/min × 106 during suffusion of GDE
(10%) alone to 34.5 ± 8.1 ml/min × 106 during suffusion of GDE
(10%) in the presence of RP-67580 (1 mg/kg iv; Fig.
2B; each group,
n = 4;
P < 0.05). CP-96344 had no
significant effects on GDE (10%)-induced responses (Fig.
3A; each
group, n = 4;
P > 0.5).
|
|
Specificity of NK1-Receptor-Antagonist-Induced Responses
CP-96345 had no significant effects on adenosine-induced increase in clearance of FITC-dextran from the in situ nasal mucosa (Fig. 3B; each group, n = 4; P > 0.5). Clearance of FITC-dextran was 34.1 ± 9.0 ml/min × 106 during suffusion
of adenosine (10 µM) alone and 35.8 ± 5.7 ml/min × 106 during suffusion of
adenosine (10 µM) in the presence of CP-96345 (5 mg/kg iv; Fig.
3B; P > 0.5).
Suffusion of substance P (1 and 10 µM) elicited a significant,
concentration-dependent increase in clearance of FITC-dextran from the
nasal mucosa (Fig. 4,
A and
B; each group,
n = 4;
P < 0.05). This response was
significantly attenuated by CP-96345 and RP-67580 (Fig. 4,
A and
B; P < 0.05). Clearance of FITC-dextran decreased from 57.9 ± 12.6 ml/min × 106 during
suffusion of substance P (10 µM) alone to 39.8 ± 7.8 ml/min × 106 during
suffusion of substance P (10 µM) in the presence of CP-96345 (5 mg/kg
iv; Fig. 4A; each group,
n = 4;
P < 0.05). Similarly, clearance of
FITC-dextran decreased from 91.7 ± 2.0 ml/min × 106 during suffusion of
substance P (10 µM) alone to 59.9 ± 16.8 ml/min × 106 during suffusion of
substance P (10 µM) in the presence of RP-67580 (1 mg/kg
iv; Fig. 4A; each group,
n = 4;
P < 0.05). CP-96344 (5 mg/kg iv) had
no significant effects on substance P (1 µM)-induced responses (Fig.
4C; each group,
n = 4;
P>0.5).
|
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
There are several new findings of this study. I found that suffusion of GDE, a prevalent environmental toxicant in the farming industry (3, 4, 11, 28, 31, 32), increases macromolecular efflux from the in situ hamster nasal mucosa microcirculation. This response is not related to nonspecific damage to the endothelium, because clearance of FITC-dextran returns to baseline once suffusion of the extract is stopped. Importantly, GDE appears to stimulate sensory nerves in the nasal mucosa to release substance P, because two structurally distinct, nonpeptide NK1-receptor antagonists, CP-96345 and RP-67580, significantly attenuate its effects, and because CP-96344, the 2R,3R enantiomer of CP-96345, is ineffective. Moreover, CP-96345 has no significant effects on adenosine-induced increase in clearance of macromolecules from the in situ nasal mucosa, whereas both CP-96345 and RP-67580, but not CP-96344, significantly attenuate substance P-induced responses. On balance, these data suggest that grain sorghum dust elicits neurogenic plasma exudation from the in situ hamster nasal mucosa. This process may underlie, in part, acute nasal obstruction observed in people exposed to grain sorghum dust.
The hamster is an established model to investigate mechanisms underlying airway mucosa injury and inflammation elicited by environmental toxicants, including grain dust (7, 8, 11, 17, 19, 25, 34). For instance, Kilburn et al. (17) showed that exposure of hamsters to an aqueous extract of cotton mill dust is associated with leukocyte recruitment into the lower airway mucosa. Gao et al. (11) showed recently that an aqueous extract of grain sorghum dust similar to that used in the present study elicits neurogenic plasma exudation from the in situ oral mucosa of hamsters. However, these data may not be extrapolated to the nose, because the oral mucosa is structurally and functionally distinct from that in the nose and because grain sorghum dust particles are deposited predominantly on the nasal mucosa (3-5, 15, 21, 28).
The results of the present study extend these observations by showing that suffusion of GDE elicits neurogenic plasma exudation from the in situ hamster nasal mucosa. The entire left nasal cavity is suffused with the extract at a constant flow rate during the experiment, thereby minimizing regional variability in clearance of FITC-dextran, the intravascular tracer used in this study (10, 23), from the nasal mucosa. In addition, we used 70-kDa FITC-dextran rather than 150-kDa FITC-dextran as the intravascular tracer because Gawlowski et al. (12) showed that in hamsters 150-kDa FITC-dextran activates circulating leukocytes, which are thought to play a role in the pathophysiology of allergic rhinitis (18) and promotes microvascular transport independent of subsequent exposure to phlogistic mediators. Overall, these data indicate that the hamster is a suitable model to investigate the mechanisms underlying nasal mucosa irritation elicited by grain sorghum dust in vivo.
Changes in vasomotor tone and/or venular driving pressure may have mediated, in part, GDE-, adenosine-, and substance P-induced increases in clearance of FITC-dextran from the in situ hamster nasal mucosa. However, this possibility seems unlikely because Gao et al. (8) showed recently that suffusion of phenylephrine, a potent vasoconstrictor, has no significant effects on bradykinin- and adenosine-induced increases in clearance of FITC-dextran from the in situ hamster nasal mucosa. Studies in other vascular beds and species have also dissociated changes in vasomotor tone from macromolecular transport (24, 26, 30, 33). Taken together, these data suggest that increases in clearance of macromolecules elicited by GDE, adenosine, and substance P from the in situ hamster nasal mucosa could not be attributed to local changes in vasomotor tone and/or venular driving pressure.
The constituents of GDE that stimulate sensory nerves in the in situ hamster nasal mucosa to release substance P, and the intracellular signaling pathway(s) that transduces the subsequent increase in macromolecular efflux, were not elucidated in this study. Conceivably, endotoxin and tannins, two major constituents of grain sorghum dust (16, 17, 31), could stimulate sensory nerves to release substance P and perhaps other tachykinins in the nasal mucosa. To this end, I (7) showed recently that tannic acid elicits neurogenic plasma exudation from the in situ hamster cheek pouch.
Importantly, Gao et al. (8, 9) showed that substance P- and bradykinin-induced increases in clearance of FITC-dextran from the in situ hamster cheek pouch and nasal mucosa, respectively, are mediated by the L-arginine/nitric oxide (NO) biosynthetic pathway. Cyclooxygenase products of arachidonic acid metabolism contributed little to substance P-induced response (9). On balance, these data suggest that tannins in grain sorghum dust could elicit neurogenic plasma exudation from the nasal mucosa microcirculation, which is transduced, in part, by the L-arginine/NO biosynthetic pathway.
The above notwithstanding, substance P may also stimulate other resident and migrant cells in the nasal mucosa, such as mast cells, to release potent phlogistic mediators, including histamine (1, 20, 27, 29). Conceivably, these mediators could activate the L-arginine/NO biosynthetic pathway, thereby increasing macromolecular efflux from the nasal mucosa (8, 10, 22). Clearly, additional studies are warranted to support or refute this hypothesis.
In summary, I found that GDE elicits neurogenic plasma exudation from the in situ hamster nasal mucosa. I suggest that this process underlies, in part, acute nasal obstruction observed in people exposed to grain sorghum dust.
| |
ACKNOWLEDGEMENTS |
|---|
I thank S. Pakhlevaniants for technical assistance; Drs. S. G. Von Essen, R. M. Snider, and C. Garret for providing grain sorghum dust, CP-96345 and CP-96344, and RP-67580, respectively; and Dr. I. Rubinstein for reviewing the manuscript.
| |
FOOTNOTES |
|---|
This study was supported, in part, by a grant from the American Heart Association of Metropolitan Chicago.
Address for reprint requests: X.-p. Gao, Dept. of Medicine (M/C 787), Univ. of Illinois at Chicago, 840 South Wood St., Chicago, IL 60612-7323.
Received 25 June 1997; accepted in final form 3 December 1997.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
1.
Bertrand, C.,
P. Geppetti,
J. Baker,
G. Petersson,
G. Piedimonte,
and
J. A. Nadel.
Role of peptidases and NK1 receptors in vascular extravasation induced by bradykinin in rat nasal mucosa.
J. Appl. Physiol.
74:
2456-2461,
1993
2.
Chaen, T.,
N. Watanabe,
G. Mogi,
K. Mori,
and
M. Takeyama.
Substance P and vasoactive intestinal peptide in nasal secretions and plasma from patients with nasal allergy.
Ann. Otol. Rhinol. Laryngol.
102:
16-21,
1993[Medline].
3.
Chan-Young, M.,
D. A. Enarson,
and
S. M. Kennedy.
The impact of grain dust on respiratory health.
Am. Rev. Respir. Dis.
145:
476-487,
1992[Medline].
4.
Clapp, W. D.,
P. S. Thorne,
K. L. Frees,
X. Zhang,
C. R. Lux,
and
D. A. Schwartz.
The effects of inhalation of grain sorghum dust extract and endotoxin on upper and lower airways.
Chest
104:
825-830,
1993
5.
Darke, C. S.,
J. Knowelden,
J. Lacey,
and
A. Milford-Ward.
Respiratory disease of workers harvesting grain.
Thorax
31:
294-302,
1976
6.
Donnerrer, J.,
R. Schuligoi,
and
C. Stein.
Increased content and transport of substance P and calcitonin gene-related peptide in sensory nerves innervating inflamed tissue: evidence for a regulatory function of nerve growth factor in vivo.
Neuroscience
49:
693-698,
1992[Medline].
7.
Gao, X.-p.
Tannic acid elicits neurogenic plasma exudation from the in situ hamster cheek pouch.
Am. J. Physiol.
274 (Regulatory Integrative Comp. Physiol. 43):
R237-R242,
1998
8.
Gao, X.-p.,
S. R. Akhter,
and
I. Rubinstein.
Ovalbumin increases macromolecular efflux from the in situ nasal mucosa of allergic hamsters.
J. Appl. Physiol.
84:
169-176,
1998
9.
Gao, X.-p.,
H. A. Jaffe,
C. O. Olopade,
and
I. Rubinstein.
Stable VIP analogue Ro 24-9981 potentiates substance P-induced plasma exudation in hamster cheek pouch.
J. Appl. Physiol.
79:
968-974,
1995
10.
Gao, X.-p.,
R. A. Robbins,
R. M. Snider,
J. Lowe III,
S. I. Rennard,
P. Anding,
and
I. Rubinstein.
NK1 receptors mediate tachykinin-induced increase in microvascular clearance in hamster cheek pouch.
Am. J. Physiol.
265 (Heart Circ. Physiol. 34):
H593-H598,
1993
11.
Gao, X.-p.,
S. Von Essen,
and
I. Rubinstein.
Neurogenic plasma exudation mediates grain dust-induced tissue injury in vivo.
Am. J. Physiol.
272 (Regulatory Integrative Comp. Physiol. 41):
R475-R481,
1997
12.
Gawlowski, D. M.,
N. R. Harding,
and
H. J. Granger.
Leukocyte phagocytosis and alterations in microvascular integrity elicited by FITC-dextran 150 and epi-illumination in the microcirculation of the hamster cheek pouch.
Microvasc. Res.
37:
1-15,
1989[Medline].
13.
Geppetti, P.,
B. M. Fusco,
S. Marabini,
C. A. Maggi,
M. Fanciullacci,
and
F. Sicuteri.
Secretion, pain and sneezing induced by the application of capsaicin to the nasal mucosa in man.
Br. J. Pharmacol.
93:
509-514,
1988[Medline].
14.
Hauser-Kronenberger, C.,
G. W. Hacker,
W. Muss,
A. Saria,
and
K. Albegger.
Autonomic and peptidergic innervation of human nasal mucosa.
Acta Otolaryngol. (Stockh.)
113:
387-393,
1993[Medline].
15.
Hurst, T. S.,
and
J. A. Dosman.
Characterization of health effects of grain dust exposures.
Am. J. Ind. Med.
17:
27-32,
1990[Medline].
16.
Jarreau, P.-H.,
M.-P. d'Ortho,
V. Boyer,
A. Harf,
and
I. Macquin-Mavier.
Effects of capsaicin on the airway responses to inhaled endotoxin in the guinea pig.
Am. J. Respir. Crit. Care Med.
149:
128-133,
1994[Abstract].
17.
Kilburn, K. H.,
W. S. Lynn,
L. L. Tres,
and
W. N. McKenzie.
Leukocyte recruitment through airway walls by condensed vegetable tannins and quercetin.
Lab. Invest.
28:
55-59,
1973[Medline].
18.
Kopke, R. D.,
and
R. L. Jackson.
Rhinitis. Head and Neck Surgery-Otolaryngology (1st ed.), edited by B. J. Bailey. Philadelphia, PA: Lippincott, 1993, p. 269-289.
19.
Latendresse, J. R.,
G. B. Marit,
E. H. Vernot,
C. C. Haun,
and
C. D. Flemming.
Oncogenic potential of inhaled hydrazine in the nose of rats and hamsters after 1 or 10 1-hr exposures.
Fundam. Appl. Toxicol.
27:
33-48,
1995[Medline].
20.
Lundblad, L.
Protective reflexes and vascular effects in the nasal mucosa elicited by activation of capsaicin-sensitive substance P-immunoreactive trigeminal neurons.
Acta Physiol. Scand. Suppl.
529:
1-42,
1984[Medline].
21.
Manfreda, J.,
V. Holford-Strevens,
M. Cheang,
and
C. P. W. Warren.
Acute symptoms following exposure to grain dust in farming.
Environ. Health Perspect.
66:
73-80,
1986[Medline].
22.
Mayhan, W. G.
Nitric oxide accounts for histamine-induced increases in macromolecular extravasation.
Am. J. Physiol.
266 (Heart Circ. Physiol. 35):
H2369-H2373,
1994
23.
Mayhan, W. G.,
and
W. L. Joyner.
The effect of altering the external calcium concentration and a calcium channel blocker, verapamil, on microvascular leaky sites and dextran clearance in the hamster cheek pouch.
Microvasc. Res.
28:
159-179,
1984[Medline].
24.
Miller, F. N.,
I. G. Joshua,
and
G. L. Anderson.
Quantitation of vasodilator-induced macromolecular leakage by in vivo fluorescent microscopy.
Microvasc. Res.
24:
56-67,
1982[Medline].
25.
Morris, J. B.,
and
D. G. Cavanagh.
Metabolism and deposition of propanol and acetone vapors in the upper respiratory tract of the hamster.
Fundam. Appl. Toxicol.
9:
34-40,
1987[Medline].
26.
Murray, M. A.,
D. D. Heistad,
and
W. G. Mayhan.
Role of protein kinase C in bradykinin-induced increase in microvascular permeability.
Circ. Res.
68:
1340-1348,
1990
27.
Persson, C. G. A.,
I. Erjefält,
U. Alkner,
C. Baumgarten,
L. Greiff,
B. Gustafsson,
A. Luts,
U. Pipkorn,
F. Sundler,
C. Svensson,
and
P. Wollmer.
Plasma exudation as a first line respiratory mucosal defence.
Clin. Exp. Allergy
21:
17-24,
1991[Medline].
28.
Rankin, J.,
J. Bates,
A. Claremont,
W. Dennis,
G. A. doPico,
D. Flaherty,
W. Reddan,
C. Reed,
P. Roa,
and
A. Tsiatis.
Study of the Prevalence of Chronic, Non-specific Lung Disease and Related Health Problems in the Grain Handling Industry. Washington, DC: Dept. Health and Human Services (National Institute on Occupational Safety and Health), 1986. (Publ. no. 86-117)
29.
Saria, A.,
J. M. Lundberg,
G. Skofitch,
and
F. Lembeck.
Vascular leakage in various tissues induced by substance P, capsaicin, bradykinin, serotonin, histamine and by antigen challenge.
Naunyn Schmiedebergs Arch. Pharmacol.
324:
212-218,
1983[Medline].
30.
Tomeo, A. C.,
and
W. N. Durán.
Resistance and exchange microvessels are modulated by different PAF receptors.
Am. J. Physiol.
261 (Heart Circ. Physiol. 30):
H1648-H1652,
1991
31.
Von Essen, S. G.,
D. P. O'Neill,
R. A. Robbins,
and
S. I. Rennard.
Neutrophil chemotaxis to extracts of grain plant components.
Am. J. Ind. Med.
25:
85-88,
1994[Medline].
32.
Von Essen, S. G.,
R. A. Robbins,
A. B. Thompson,
R. F. Ertl,
J. Linder,
and
S. Rennard.
Mechanisms of neutrophil recruitment to the lung by grain dust exposure.
Am. Rev. Respir. Dis.
138:
921-927,
1988[Medline].
33.
Warren, J. B.,
A. J. Wilson,
R. K. Loi,
and
M. L. Coughlan.
Opposing roles of cyclic AMP in the vascular control of edema formation.
FASEB J.
7:
1394-1400,
1993[Abstract].
34.
Witschi, H.,
D. W. Wilson,
and
C. G. Plopper.
Modulation of N-nitrosodiethylamine-induced hamster lung tumors by ozone.
Toxicology
77:
193-202,
1993[Medline].
This article has been cited by other articles:
|
|
 |
|
  J. N. Kline, P. J. Jagielo, J. L. Watt, and D. A. Schwartz Bronchial hyperreactivity is associated with enhanced grain dust-induced airflow obstruction J Appl Physiol, September 1, 2000; 89(3): 1172 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Akhter, H. Ikezaki, X.-P. Gao, and I. Rubinstein Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo J Appl Physiol, May 1, 1999; 86(5): 1603 - 1609. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
P < 0.05 vs. GDE alone.
