Differential response of the pulmonary circulation to prostaglandins E2 and F2 alpha in the presence of unilateral alveolar hypoxia.
Pulmonary hemodynamic responses to several prostaglandins (PGs) are augmented by hypoxia. To test whether responses to vasoconstrictor PGs would be enhanced in hypoxic areas of the lung, resulting in redistribution of blood flow to well-oxygenated areas, the effects of PGE2 and PGF2 alpha were evaluated in anesthetized dogs with divided ventilation, one lung being ventilated with 100% N2 and the other with 100% O2. Thermal dilution techniques coupled with electromagnetic flow measurements permitted estimates of blood flow to each lung. After indomethacin (5 mg/kg i.v.), PGE2 at 0.01, 0.025 and 0.10 micrograms/kg/min i.v. produced significant increases in flow to the O2-ventilated lung at each dose. In addition, PGE2 increased total pulmonary blood flow, but only at the two larger doses. Concomitantly, systemic arterial PO2 increased from 104 +/- 21 to 138 +/- 26 mm Hg (P less than .001). Identical results were obtained when meclofenamate (5 mg/kg i.v.) was used to block PG synthesis. PGF2 alpha increased total pulmonary blood flow (P less than .01) only at the largest dose (0.10 micrograms/kg/min), but did not redistribute flow or increase PO2. Atrial pacing increased total pulmonary blood flow (P less than .001) and flow to both O2 (P less than .001)- and N2 (P less than .05)-ventilated lungs with no change in PO2. We conclude that PGE2 redistributes pulmonary blood flow to well-oxygenated alveoli through mechanisms not related solely to its vasoconstrictor properties or to its capacity to increase cardiac output.
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D015237:Dinoprost; D015232:Dinoprostone; D004285:Dogs; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009584:Nitrogen / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects
D011458:Prostaglandins E; D011460:Prostaglandins F; D008469:Meclofenamic Acid; D015237:Dinoprost; D015232:Dinoprostone; D009584:Nitrogen; D010100:Oxygen; D007213:Indomethacin