Reversal of 5HT-induced bronchoconstriction by PGI₂: Distribution of central and peripheral actions

In anesthetized, mechanically ventilated, and vagotomized cats, we studied the distribution of the bronchodilatory effects of prostaglandin I₂ (PGI₂) in central and peripheral airways. In the intact-chest cat, bolus intravenous injection of PGI₂ in a range of doses from 3 to 100 μg produced dose-dependent reversal of 5-hydroxytryptamine- (5HT) induced bronchoconstriction. Bronchodilatory effects were manifested by a pronounced decrease in central airways flow resistance, as estimated by measurement of lung resistance and by an increase in dynamic lung compliance (Cdyn). A similar distribution and magnitude of airway effects were produced by intravenous administration of PGE₁ in a range of doses from 0.3 to 10 μg. PGI₂ significantly reversed the frequency dependence of compliance induced by infusion of 5HT. The PGI₂ metabolite, 6-keto-PGF₁(α), was without effect on pulmonary mechanics. Comparison of right- versus left-heart administration of PGI₂ did not point to a significant role of the bronchial circulation in the airway effects of PGI₂. Comparison of the effects of PGI₂ and PGE₁ on cat bronchial and parenchymal strips contracted by 5HT showed both prostaglandins to have predominant action on bronchial smooth muscle with PGI₂ being 3-10 times less active than PGE₁. These data suggest that PGI₂ has central airway bronchodilator activity, similar to, but less potent than PGE₁. In addition, they suggest that PGI₂ has significant dilator activity in certain peripheral areas of the lung, as well.