The mechanisms behind bradykinin-induced effects in the airways are considered to be largely indirect. The role of cholinergic nerves and eicosanoids, and their relationship in these mechanisms were investigated in guinea-pigs. 2. The role of cholinergic nerves was studied in animals given atropine (1 mg kg-1, i.v.), hexamethonium (2 mg kg-1, i.v.), or vagotomized. To study the role of eicosanoids, animals were pretreated with a thromboxane A2 (TxA2) receptor antagonist (ICI 192,605; 10(-6) mol kg-1, i.v.) or with a leukotriene (LT) receptor C4/D4/E4 antagonist (ICI 198,615; 10(-6) mol kg-1, i.v.). 3. After pretreatment with a drug, bradykinin (150 nmol) was instilled into the tracheal lumen. We measured both airway insufflation pressure (Pi), to assess airway narrowing, and the content of Evans blue dye in airway tissue, to assess plasma exudation. 4. Bradykinin instillation into the trachea caused an increase in Pi and extravasation of Evans blue dye. The increase in Pi was significantly attenuated by atropine or the TxA2 receptor antagonist, but not by hexamethonium, vagotomy or the LT receptor antagonist. 5. The bradykinin-induced exudation of Evans blue dye was significantly attenuated in the intrapulmonary airways by the TxA2 receptor antagonist, but not by atropine, hexamethonium, cervical vagotomy or the LT receptor antagonist. 6. A thromboxane-mimetic U-46619 (20 nmol kg-1, i.v. or 10 nmol intratracheally), caused both an increase in Pi and extravasation of Evans blue dye at all airway levels. Atropine pretreatment slightly attenuated the peak Pi after the intratracheal administration of U-46619, but not after i.v. administration. 7. We conclude that peripheral cholinergic nerves are involved in bradykinin-induced airflow obstruction but not plasma exudation, and that TxA2 is involved in both airflow obstruction and airway plasma exudation induced by bradykinin given via the airway route. TxA2-induced airflow obstruction is mediated only to a minor degree, via the release of acetylcholine in the airways.
