Bronchopulmonary effects of prostaglandin F2alpha and three of its metabolites in the dog.

The airway and lung dynamics of porstaglandin F2alpha (PGF2alpha) and three of its metabolites were examined in the spontaneously ventilated, pentobarital anesthetized dog. Changes in expirtaory 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 mu/kg i.v., PGF2alpha and its 13, 14-dihydrometabolite were found to be exceptionally potent agents. This metabolite was approximately twice as potent as PGF2alpha on most parameters studied. Two other metabolites, 15-keto-PGF2alpha and 15-keto-13, 14-dihydro-PGF2alpha, were only slightly effective, even in a dose range of 1.0-30.0 mu/kg i.v. These latter two metabolites produced dose-response curves with significantly shallower slopes than PGF2alpha and were shown to be at least thirty-five times less potent than the parent compound. Therefore, oxidation of PGF2alpha at the carbon-15 position by 15-hydroxy prostaglandin dehydrogenase appears to produce compounds with minimal in vivo bronchopulomary activity.