Effects of Cilostazol, a Cyclic Nucleotide Phosphodiesterase III Inhibitor, on Substance P-lnduced Airflow Obstruction and Airway Microvascular Leakage in Guinea Pigs

Pharmacology ◽  
1994 ◽  
Vol 48 (5) ◽  
pp. 301-307 ◽  
Author(s):  
Kenichi Tokuyama ◽  
Tatsuya Yokoyama ◽  
Hirokazu Arakawa ◽  
Akihiro Morikawa ◽  
Takayoshi Kuroume
Keyword(s):  
Substance P ◽  
Cyclic Nucleotide ◽  
Guinea Pigs ◽  
Airflow Obstruction ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Microvascular Leakage ◽  
Phosphodiesterase Iii Inhibitor ◽  
Phosphodiesterase Iii

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.

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

Effects of STA2, a Thromboxane A2 Mimetic, in Inducing Airflow Obstruction and Airway Microvascular Leakage in Guinea Pigs

Pharmacology ◽  
2002 ◽  
Vol 65 (2) ◽  
pp. 62-68 ◽  
Author(s):  
Yoshinari Inoue ◽  
Kenichi Tokuyama ◽  
Hideko Nishimura ◽  
Hirokazu Arakawa ◽  
Masahiko Kato ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Airflow Obstruction ◽  
Microvascular Leakage

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
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