Effects of Prostaglandin Cyclic Endoperoxides on the Lung Circulation of Unanesthetized Sheep

Abstract

A B S T R A C T Although prostaglandins E2 and F2, have been suggested as mediators of the pulmonary hypertension seen after endotoxin infusion or during alveolar hypoxia, their precursors, the endoperoxides (prostaglandins G2 and H2) are much more potent vaso- constrictors in vitro. In this study we compared the effects of prostaglandin (PG)H2, a stable 9-methylene ether analogue of PGH2 (PGH2-A), PGE2, and PGF2a on pulmonary hemodynamics in awake sheep. The animals were prepared to allow for measurement of (a) lung lymph flow; (b) plasma and lymph protein concentration; (c) systemic and pulmonary vascular pres- sures; and (d) cardiac output. We also determined the effect of prolonged PGH2-A infusions on lung fluid balance and vascular permeability by indicator dilu- tion methods, and by assessing the response of lung lymph. Both PGH2 and PGH2-A caused a dose-related increase in pulmonary artery pressure: 0.25 ,ug/kg x min tripled pulmonary vascular resistance without substantially affecting systemic pressures. Both were 100 times more potent than PGE2 or PGF2,, in this prepara- tion. ?GH2-A, as our analysis of lung lymph and indica- tor dilution measurements show, does not increase the permeability of exchanging vessels in the lung to fluid and protein. It does, however, augment lung fluid trans- port by increasing hydrostatic pressure in the pul- monary circulation. We conclude: (a) that PGH2 is likely to be an important mediator of pulmonary vaso- constriction; (b) its effects are probably not a result of its metabolites PGE2 or PGF,.