Analysis of airway responses to A23187 in the cat

Airway responses to ionophore A23187 were investigated in anesthetized, paralyzed cats under conditions of controlled ventilation. Intravenous injections of A23187 caused dose-related increases in transpulmonary pressure and lung resistance and dose-related decreases in dynamic compliance and aortic pressure. Airway responses to A23187 were reduced by sodium meclofenamate, a cyclooxygenase inhibitor, in a dose that decreased bronchomotor responses to the prostaglandin precursor, arachidonic acid. The cyclooxygenase inhibitor had no significant effect on airway responses to U-46619, a prostaglandin endoperoxide analog whose actions mimic those of thromboxane A2. Bronchomotor responses to ionophore A23187 were also reduced by SQ 29,548, a thromboxane receptor antagonist. SQ 29,548 reduced airway responses to the thromboxane A2 mimic, U-46619, but had no significant effect on airway responses to prostaglandins D2 or F2 alpha. These data indicate that ionophore A23187 constricts smooth muscle in central airways and in peripheral portions of the lung. In addition, these results suggest that in the closed-chest cat, bronchoconstrictor responses to A23187 are mediated mainly by formation of cyclooxygenase products and that a substantial part of the response is due to thromboxane A2 formation.