8-Epi-PGF2alpha induces airflow obstruction and airway plasma exudation in vivo.
8-Epi-prostaglandin F2alpha (8-epi-PGF2alpha) is an F2-isoprostane formed mainly via noncyclooxygenase pathways in vivo. We investigated whether 8-epi-PGF2alpha has any effect on airflow obstruction and plasma exudation in vivo. Airflow obstruction was quantified by measuring lung resistance (RL) in anesthetized and ventilated guinea pigs, and plasma exudation was quantified by the Evans Blue dye method (20 mg/kg intravenously). Intratracheal instillation of 8-epi-PGF2alpha (1 nmol or 10 nmol) caused dose-related increases in RL. Furthermore, the higher dose of 8-epi-PGF2alpha produced Evans Blue dye extravasation in main bronchi and intrapulmonary airways. A prostanoid TP-receptor antagonist, BAY u3405 (1 mg/kg intravenously), abolished the airway effects of 8-epi-PGF2alpha (10 nmol). A thromboxane A2 (TxA2) synthase inhibitor, OKY-406 (30 mg/kg intravenously), significantly attenuated these effects of 8-epi-PGF2alpha (10 nmol). The level of TxB2, a stable TxA2 metabolite, increased in bronchoalveolar lavage fluid (BALF) after 8-epi-PGF2alpha instillation. We conclude that 8-epi-PGF2alpha causes airflow obstruction and plasma exudation in vivo. This effect may be mediated primarily via prostanoid TP-receptors, and a secondary generation of TxA2 may be involved in part of the airway responses in 8-epi-PGF2alpha in the guinea pig.
Okazawa
A
A
Department of Respiratory Medicine and Allergology, Institute of Heart and Lung Diseases, Goteborg University, Gothenburg, Sweden.
Kawikova
I
I
Cui
Z H
ZH
Skoogh
B E
BE
Lötvall
J
J
D000402:Airway Obstruction / Q000139:chemically induced*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002227:Carbazoles / Q000494:pharmacology; D015237:Dinoprost / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000032:analysis; D014662:Vasoconstrictor Agents / Q000009:adverse effects* / Q000037:antagonists & inhibitors
D002227:Carbazoles; D006633:Histamine Antagonists; D008689:Methacrylates; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; D013928:Thromboxane A2; D015237:Dinoprost; C034364:ozagrel; C063119:ramatroban