Zymosan activation of plasma reduces hypoxic pulmonary vasoconstriction.
Small doses of endotoxin (15 micrograms/kg IV) inhibit the pulmonary vascular pressor response to alveolar hypoxia in the anesthetized dog. One of the actions of endotoxin is to initiate the alternate pathway of complement activation. Incubation of human plasma with zymosan (ZAP) will activate this pathway. We wished to see if ZAP would mimic the effect of endotoxin. Prior to ZAP, hypoxia (F1O2 12%) in 5 anesthetized dogs increased pulmonary vascular resistance (PVR: mm Hg/L/min) from 3.7 +/- 0.8 to 7.1 +/- 1.5. After 50 ml ZAP IV the PVR change with hypoxia was only from 3.6 +/- 0.6 to 3.9 +/- 0.8. Plasma heated to destroy complement prior to ZAP incubation in one experiment did not reduce the pressor response. In a further 5 dogs pretreated with meclofenamate (2 mg/kg IV) the PVR increased from 3.7 +/- 0.4 to 7.5 +/- 0.4 with hypoxia prior to IV ZAP and from 4.4 +/- 0.5 to 6.5 +/- 0.6 after ZAP. The effect of ZAP indicates that endotoxin may work through the activation of complement. The protection of the hypoxic pressor response by meclofenamate suggests that the ZAP inhibition (like endotoxin inhibition) may involve dilator prostaglandin-like substances.
D000818:Animals; D003167:Complement Activation / Q000187:drug effects*; D004285:Dogs; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D010949:Plasma / Q000187:drug effects*; D011652:Pulmonary Circulation; D014661:Vasoconstriction / Q000187:drug effects*; D015054:Zymosan / Q000494:pharmacology*
D004731:Endotoxins; D008469:Meclofenamic Acid; D015054:Zymosan