title: Endotoxin and prevention of hypoxic pulmonary vasoconstriction.
abstract: Endotoxin is known both to stimulate prostaglandin production and to abolish the pulmonary vascular pressor response to hypoxia. The present study demonstrated that two inhibitors of prostaglandin synthesis, meclofenamate and indomethacin, prevent loss of pulmonary vasoconstriction due to hypoxia when sublethal doses of endotoxin are administered. This suggests that endotoxin may stimulate the production of a dilator prostaglandin which would oppose the hypoxic vasoconstriction, but other ways in which these inhibitor drugs might act are considered. Endotoxin damages platelets and leukocytes, both of which can form prostaglandins and could be the source of a dilator prostaglandin. However, in these experiments endotoxin abolished the hypoxic pressor response in dogs rendered severely thrombocytopenic by platelet antiserum. This suggests that platelets are not involved. In further experiments blood from anesthetized dogs was circulated through glass bead columns. Changes in the leukocyte count following perfusion were correlated with changes in the subsequent pressor response to hypoxia. The possibility that leukocytes may be involved in the effect of endotoxin on the hypoxic pressor response is considered.
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects; D008469:Meclofenamic Acid / Q000494:pharmacology; D011448:Prostaglandin Antagonists; D011453:Prostaglandins / Q000096:biosynthesis; D011651:Pulmonary Artery / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
chemical_list: D004731:Endotoxins; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D008469:Meclofenamic Acid; D007213:Indomethacin