6-keto-PGE1 exhibits more potent bronchodilatory activity in the cat than its precursor, PGI2.
In anesthetized, vagotomized an mechanically ventilated cats, we investigated the bronchodilatory activity of the PGI2 metabolite, 6-keto-PGE1, relative to PGI2 and PGE2. In a range of doses from 0.3-10.0 microgram, i.v. injection of 6-keto-PGE1 produced a dose-related decrease in central airway resistance (RL) in animals bronchoconstricted by 5-HT. This effect on RL was 3-10 times greater than that produced by i.v. PGI2. At the lower doses, 6-keto-PGE1 was also more potent than PGI2 in increasing dynamic lung compliance; their effects upon semi-static compliance were not significantly different. Comparison of the bronchopulmonary effects of the two prostanoids did not show any consistent difference in their temporal patterns. In contrast to PGI2 or PGE2, 6-keto-PGE1 had minimal pulmonary vasomotor activity. Inhibition of the cyclooxygenase pathway with sodium meclofenamate had no effect on the bronchopulmonary actions of 6-keto-PGE1 or on its duration of action. These data indicate that 6-keto-PGE1 is a more potent bronchodilator than PGI2 in the cat. They further suggest that conversion of PGI2 to 6-keto-PGE1, if it occurs to an appreciable extent in the lung in vivo, could enhance bronchodilatory activity.
D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology
D001993:Bronchodilator Agents; D011453:Prostaglandins; D011458:Prostaglandins E; D012701:Serotonin; C022950:6-ketoprostaglandin E1; D011464:Epoprostenol; D000527:Alprostadil