Role of thromboxane A2 in airway microvascular leakage induced by inhaled platelet-activating factor.
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.
Tokuyama
K
K
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Lötvall
J O
JO
Morikawa
A
A
Barnes
P J
PJ
Chung
K F
KF
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane; D012137:Respiratory System / Q000098:blood supply*; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D004146:Dioxanes; D008689:Methacrylates; D010972:Platelet Activating Factor; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C057498:ICI 192605; D013928:Thromboxane A2; D006632:Histamine; D013930:Thromboxane-A Synthase; C034364:ozagrel