Acute effects of prostaglandin D2 to induce airflow obstruction and airway microvascular leakage in guinea pigs: role of thromboxane A2 receptors

2001 ◽  
Vol 66 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Hideko Nishimura ◽  
Kenichi Tokuyama ◽  
Yoshinari Inoue ◽  
Hirokazu Arakawa ◽  
Masahiko Kato ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Airflow Obstruction ◽  
Thromboxane A2 ◽  
Prostaglandin D2 ◽  
Acute Effects ◽  
Microvascular Leakage ◽  
A2 Receptors

Role of thromboxane A2 in airway microvascular leakage induced by inhaled platelet-activating factor

1991 ◽  
Vol 71 (5) ◽  
pp. 1729-1734 ◽  
Author(s):  
K. Tokuyama ◽  
J. O. Lotvall ◽  
A. Morikawa ◽  
P. J. Barnes ◽  
K. F. Chung
Keyword(s):  
Airflow Obstruction ◽  
Platelet Activating Factor ◽  
Thromboxane A2 ◽  
Blue Dye ◽  
Dependent Manner ◽  
Thromboxane A2 Receptor ◽  
Microvascular Leakage ◽  
Thromboxane Synthase Inhibitor ◽  
Synthase Inhibitor

We studied the effects of OKY-046 (1, 10, and 30 mg/kg iv), a selective thromboxane synthase inhibitor, and of ICI 192605 (0.5 mg/kg), a selective thromboxane A2 receptor antagonist, on airflow obstruction and airway microvascular leakage induced by inhaled platelet-activating factor (PAF). Extravasated Evans blue dye content was measured as a reflection of airway microvascular leakage. In control animals, PAF caused a significantly higher increase in extravasation of dye and significantly less increase in lung resistance (RL) than histamine. OKY-046 significantly inhibited both changes in RL and airway microvascular leakage after PAF in a dose-dependent manner, whereas it inhibited histamine-induced airway microvascular leakage only at main bronchi, without any significant effect on RL. ICI 192605 significantly inhibited both RL and airway microvascular leakage induced by PAF, but not after histamine. After both PAF and histamine, changes in RL correlated significantly with the degree of microvascular leakage. Airway microvascular leakage and airflow obstruction after PAF, but not after histamine, may be dependent on thromboxane A2 generation.

scholarly journals Role of thromboxane A2 in the development of antigen-induced long-lasting bronchial hyperresponsiveness in actively sensitized guinea pigs.

Ensho ◽  
1994 ◽  
Vol 14 (3) ◽  
pp. 213-219
Author(s):  
Akinori Arimura ◽  
Asanuma Fujio ◽  
Atsushi Kurosawa ◽  
Hirokuni Jyoyama
Keyword(s):  
Guinea Pigs ◽  
Bronchial Hyperresponsiveness ◽  
Thromboxane A2

Bradykinin is less potent in causing airway microvascular leakage in immature than in adult guinea-pigs. Role of neutral endopeptidase

1993 ◽  
Vol 236 (3) ◽  
pp. 427-432 ◽  
Author(s):  
Tatsuya Yokoyama ◽  
Kenichi Tokuyama ◽  
Akihiro Morikawa ◽  
Takayoshi Kuroume
Keyword(s):  
Guinea Pigs ◽  
Neutral Endopeptidase ◽  
Microvascular Leakage

Effects of Y-27632, a Rho/Rho Kinase Inhibitor, on Leukotriene D4- and Histamine-Induced Airflow Obstruction and Airway Microvascular Leakage in Guinea Pigs in vivo

Pharmacology ◽  
2002 ◽  
Vol 64 (4) ◽  
pp. 189-195 ◽  
Author(s):  
Kenichi Tokuyama ◽  
Hideko Nishimura ◽  
Kunihiko Iizuka ◽  
Masahiko Kato ◽  
Hirokazu Arakawa ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Kinase Inhibitor ◽  
Airflow Obstruction ◽  
Rho Kinase ◽  
Microvascular Leakage ◽  
Rho Kinase Inhibitor

Airflow obstruction after substance P aerosol: contribution of airway and pulmonary edema

1990 ◽  
Vol 69 (4) ◽  
pp. 1473-1478 ◽  
Author(s):  
J. O. Lotvall ◽  
R. J. Lemen ◽  
K. P. Hui ◽  
P. J. Barnes ◽  
K. F. Chung
Keyword(s):  
Substance P ◽  
Pulmonary Edema ◽  
Evans Blue ◽  
Guinea Pigs ◽  
Airflow Obstruction ◽  
Maximum Effect ◽  
Blue Dye ◽  
Evans Blue Dye ◽  
Microvascular Leakage ◽  
Lung Resistance

We have studied the effects of aerosolized substance P (SP) in guinea pigs with reference to lung resistance and dynamic compliance changes and their recovery after hyperinflation. In addition, we have examined the concomitant formation of airway microvascular leakage and lung edema. Increasing breaths of SP (1.5 mg/ml, 1.1 mM), methacholine (0.15 mg/ml, 0.76 mM), or 0.9% saline were administered to tracheostomized and mechanically ventilated guinea pigs. Lung resistance (RL) increased dose dependently with a maximum effect of 963 +/- 85% of baseline values (mean +/- SE) after SP (60 breaths) and 1,388 +/- 357% after methacholine (60 breaths). After repeated hyperinflations, methacholine-treated animals returned to baseline, but after SP, mean RL was still raised (292 +/- 37%; P less than 0.005). Airway microvascular leakage, measured by extravasation of Evans Blue dye, occurred in the brain bronchi and intrapulmonary airways after SP but not after methacholine. There was a significant correlation between RL after hyperinflation and Evans Blue dye extravasation in intrapulmonary airways (distal: r = 0.89, P less than 0.005; proximal: r = 0.85, P less than 0.01). Examination of frozen sections for peribronchial and perivascular cuffs of edema and for alveolar flooding showed significant degrees of pulmonary edema for animals treated with SP compared with those treated with methacholine or saline. We conclude that the inability of hyperinflation to fully reverse changes in RL after SP may be due to the formation of both airway and pulmonary edema, which may also contribute to the deterioration in RL.

Responsiveness of the guinea pig trachea to stretch: role of the epithelium and cyclooxygenase products

1993 ◽  
Vol 75 (5) ◽  
pp. 2112-2116 ◽  
Author(s):  
Y. Gao ◽  
P. M. Vanhoutte
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Thromboxane A2 ◽  
Isometric Tension ◽  
Similar Response ◽  
Thromboxane Synthase ◽  
Prostacyclin Synthase ◽  
A2 Receptors

The role of the epithelium and cyclooxygenase products was investigated in the responses of isolated airways to sudden stretch. Strips of guinea pig trachea, in some of which the epithelium had been removed mechanically, were suspended in organ chambers; isometric tension was recorded. After rapid stretching to their optimal tension, the preparations (with and without epithelium) relaxed initially and then contracted to a level close to the imposed tension. Afterward, tissues with epithelium maintained this level of tension, but those without epithelium relaxed. After treatment with papaverine or isoproterenol (at concentrations causing maximal relaxation), stretch was followed only by a decrease in tension; a similar response to stretch was also obtained in tissues treated with indomethacin or acetylsalicylic acid (inhibitors of cyclooxygenase). Dazmegrel (an inhibitor of thromboxane synthase) and SQ-29548 (an antagonist of prostaglandin H2 or thromboxane A2 receptors) did not affect the response of tissues with epithelium but abolished the stretch-induced contraction in those without epithelium. Tranylcypromine, which inhibits prostacyclin synthase, and tetrodotoxin, which blocks local reflexes, did not significantly affect the responses of the tissues to stretch. These observations suggest that thromboxane may mediate the epithelium-independent contraction and that another product of cyclooxygenase contributes to the maintenance of tension on stretching observed in tissues with epithelium.

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