Effects of prostaglandin cyclic endoperoxides on the lung circulation of unanesthetized sheep.
Although prostaglandins E(2) and F(2alpha) have been suggested as mediators of the pulmonary hypertension seen after endotoxin infusion or during alveolar hypoxia, their precursors, the endoperoxides (prostaglandins G(2) and H(2)) are much more potent vasoconstrictors in vitro. In this study we compared the effects of prostaglandin (PG)H(2), a stable 9-methylene ether analogue of PGH(2) (PGH(2)-A), PGE(2), and PGF(2alpha) 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 PGH(2)-A infusions on lung fluid balance and vascular permeability by indicator dilution methods, and by assessing the response of lung lymph. Both PGH(2) and PGH(2)-A caused a dose-related increase in pulmonary artery pressure: 0.25 mug/kg x min tripled pulmonary vascular resistance without substantially affecting systemic pressures. Both were 100 times more potent than PGE(2) or PGF(2alpha) in this preparation. PGH(2)-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 PGH(2) is likely to be an important mediator of pulmonary vasoconstriction; (b) its effects are probably not a result of its metabolites PGE(2) or PGF(2alpha).
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D008168:Lung / Q000502:physiology; D008196:Lymph / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011463:Prostaglandins H / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H