Pulmonary vascular response to platelet-activating factor in conscious sheep

Hemodynamic response to an intravenous infusion of platelet-activating factor (PAF; 1 microgram/kg) was studied in conscious sheep with lung lymph fistulas. PAF induced increases in pulmonary arterial pressure and decreases in left atrial and systemic arterial pressures and in cardiac output, together with transient increases in thromboxane (Tx) A2 (as TxB2) and prostacyclin (as 6-keto-PGF1 alpha) values in plasma and lung lymph. There were also transient decreases in circulating leukocytes and platelets. The second infusion of PAF induced a reduced response compared with the first one, but the response to PAF was afterward maintained. Pretreatment with OKY 046, a thromboxane synthase inhibitor, reduced the first pulmonary vasoconstriction in response to PAF to a degree equivalent to that after successive infusions of PAF in control sheep. Pulmonary response to PAF (except on first infusion) and systemic cardiovascular response did not change whether or not TxA2 was produced. We therefore concluded that PAF mediates pulmonary and systemic cardiovascular effects via mechanisms other than TxA2 during successive infusions of PAF and that PAF-induced TxA2 contributes only to the pulmonary response to PAF on first infusion of the latter.