Evidence for distinct systemic extravasation effects of platelet activating factor, leukotrienes B4, C4, D4 and histamine in the guinea pig.

The relative potencies of platelet-activating factor (PAF), leukotrienes B4 (LTB4), C4 (LTC4), D4 (LTD4) and histamine to induce hemoconcentration (HC) were evaluated in the guinea pig. The maximal hematocrit increase (MHI) from PAF, LTD4 and histamine occurred 5-7 min after i.v. injection, whereas the MHI of LTC4 occurred 13-15 min after injection. LTB4 (2.97-5.95 nmol kg-1) did not produce HC. The magnitude of PAF-induced MHI was 2-fold that of LTC4 or LTD4, regardless of the dose of leukotrienes used. The doses (nmol kg-1) needed to produce 30% HC were: 0.14-PAF, 0.71-LTD4 and 3.37-LTC4 and 2,400 histamine. The HC effects of LTD4 were markedly reduced by prior administration of FPL-55712. However, neither LTC4 or LTD4 HC effects were significantly reduced by prior i.v. injection of CV-3988 (3.4 mg kg-1), a competitive receptor antagonist to PAF which is 98% effective in abolishing HC response to 0.14 nmol kg-1 PAF. Diphenhydramine abolished histamine-induced hemoconcentration but was without effect on PAF or LTD4. These results suggest that the responses of PAF, leukotrienes and histamine differ in their potency and may involve separate vascular recognition sites related to acute increases in vascular permeability.