A pathophysiological role of endogenous prostacyclin in endotoxin induced increase in lung vascular permeability in dogs.
Escherichia coli endotoxin (1 mg/kg) infusion over 30 min into anesthetized artificially ventilated dogs caused a biphasic response: an early phase of pulmonary hypertension and a late phase of increased lung vascular permeability. During an early phase, PG F2 alpha, Tx A2 (as Tx B2) and prostacyclin (as 6-keto-PG F1 alpha) concentrations increased in plasma or right duct lymph of dogs. During a late phase, the concentrations of PG F2 alpha and Tx A2 decreased to near the base-line values, while the concentration of prostacyclin remained elevated. Administrations of PG synthetase inhibitors 45 min prior to endotoxin inhibited the increase in concentration of prostacyclin following the infusion of endotoxin and potentiated the increase in lung vascular permeability at the beginning of the late phase. Continuous infusion of prostacyclin (20 ng/kg/min) starting one hour before endotoxin for 5 hour periods prevented the increase in lung vascular permeability induced by endotoxin. Based on these results, we could conclude that endogenous prostacyclin might play an important role in preserving cell integrity of lungs and counteract the deleterious effects of endotoxin.
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004285:Dogs; D004731:Endotoxins / Q000633:toxicity*; D011464:Epoprostenol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D008196:Lymph / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects*
D004731:Endotoxins; D011453:Prostaglandins; D011464:Epoprostenol