Bronchopulmonary pharmacology of some prostaglandin endoperoxide analogs in the dog.

This investigation examined quantitatively the bronchopulmonary effects of two prostaglandin endoperoxide analogs (cyclic ethers) in the spontaneously breathing, anesthetized dog. Responses to these agents were measured by computer analyses and compared to those produced by prostaglandin F2alpha (PGF2alpha). In a dose range of 0.03-1.0 mug/kg i.v., both cyclic ethers produced dose-related alterations in pulmonary airway resistance dynamic lung compliance, expiratory airflow rate, tidal volume and respiratory frequency. These pulmonary changes were significantly greater than those observed for PGF2alpha (0.3-3.0 mug/kg). The onset of activity was prompt (less than 1 min) and recovery was complete within 5-10 min. Atropine pretreatment greatly reduced the airway resistance effects of all three test agents, thus suggesting some cholinergic component to their potent bronchoconstrictor activities. These cyclic ethers are stable forms of prostaglandin endoperoxides and may represent invaluable pharmacologic tools for the further study of intermediates in prostaglandin synthesis.