Pulmonary vascular response to platelet-activating factor in awake sheep and the role of cyclooxygenase metabolites.
We examined the effects of platelet activating factor (PAF) (1.0 microgram/kg infusion for 15 min) on pulmonary hemodynamics and lung fluid balance and the role of cyclooxygenase metabolites in mediating these responses in unanesthetized sheep prepared with lung lymph fistulas. Platelet activating factor infusion resulted in immediate and transient increases in pulmonary artery pressure, pulmonary vascular resistance, and pulmonary lymph flow. The lymph-to-plasma protein concentration ratio did not change significantly from baseline. Circulating platelet and leukocyte counts decreased immediately after PAF infusion; the leukopenia was the result of a rapid decrease in both the neutrophil and mononuclear leukocyte counts. Arterial thromboxane B2 (TxB2) concentration increased after the PAF infusion, but the 6-keto prostaglandin F1 alpha (a prostacyclin degradation product) concentration did not change from baseline. A chemically similar substance, Lyso-PAF, had no effect on the pulmonary hemodynamic, lymph, and hematologic parameters or the TxB2 generation. Administration of cyclooxygenase inhibitors, meclofenamate or indomethacin, prior to PAF infusion prevented thromboxane B2 generation and attenuated the pulmonary hemodynamic response. The initial pulmonary lymph flow and transvascular protein clearance (lymph flow times lymph-to-plasma protein concentration) responses to PAF were attenuated after cyclooxygenase inhibition. However, there were time-dependent increases in pulmonary lymph flow and transvascular protein clearance in the cyclooxygenase-inhibited groups. These results indicate that PAF induces pulmonary vasoconstriction mediated by cyclooxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008196:Lymph / Q000187:drug effects / Q000502:physiology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D008469:Meclofenamic Acid; D007213:Indomethacin