Abstract
The airway and lung dynamics of prostaglandin F 2α (PGF 2α) and three of its metabolites were examined in the spontaneously-ventilated, pentobarbital anesthetized dog. Changes in expiratory flow rate, tidal volume, respiration rate, lung resistance and dynamic lung compliance were evaluated and compared quantitatively. In a dose range of 0.3–3.0 μg/kg i.v., PGF 2α and its 13,14-dihydro metabolite were found to be exceptionally potent agents. This metabolite was approximately twice as potent as PGF 2α on most parameters studied. Two other metabolites, 15-keto-PGF 2α and 15-keto-13,14-dihydro-PGF 2α, were only slightly effective, even in a dose range of 1.0–30.0 μg/kg i.v. These latter two metabolites produced dose-response curves with significantly shallower slopes than PGF 2α and were shown to be at least thirty-five times less potent than the parent compound. Therefore, oxidation of PGF 2α at the carbon-15 position by 15-hydroxy prostaglandin dehydrogenase appears to produce compounds with minimal in vivo bronchopulmonary activity.
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