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

Although prostaglandins E₂ and F_2α 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 vasoconstrictors 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 PGF_2α 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 pressures; and (d) cardiac output. We also determined the effect of prolonged PGH₂-A infusions on lung fluid balance and vascular permeability by indicator dilution 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 μg/kg × min tripled pulmonary vascular resistance without substantially affecting systemic pressures. Both were 100 times more potent than PGE₂ or PGF_2α in this preparation. PGH₂-A, as our analysis of lung lymph and indicator dilution measurements show, does not increase the permeability of exchanging vessels in the lung to fluid and protein. It does, however, augment lung fluid transport by increasing hydrostatic pressure in the pulmonary circulation. We conclude: (a) that PGH₂ is likely to be an important mediator of pulmonary vasoconstriction; (b) its effects are probably not a result of its metabolites PGE₂ or PGF_2α.