The effect of platelet-activating factor (PAF), histamine, and ethanol on vascular permeability of the guinea pig conjunctiva.

ABSTRACT

Increased vascular permeability, one of the characteristic features of immediate hypersensitivity (Type I), is mediated through a variety of compounds, including histamine and platelet-activating factor (PAF), a phospholipid inflammatory mediator. The effects on vascular permeability of histamine, PAF, and ethanol, the solvent for PAF, were compared in the guinea pig conjunctiva. Permeability at 30 min was investigated by evaluation of conjunctival edema and Evans blue extravasation (clinically estimated and colorimetrically measured). Doses of PAF from 1 to 10 nmol produced an increase in vascular permeability, with a peak effect at 10 nmol. Ethanol had no effect on vascular permeability below 40 X 10(3) nmol; above this concentration, however, permeability increased, reaching a maximum at 175 X 10(3) nmol. At low doses of PAF and ethanol, the effects were additive, whereas at 20-80 nmol of PAF with high concentrations of ethanol there was no additive effect of PAF, producing a decrease in the net effect of PAF. Histamine increased vascular permeability, with a minimum effect at 10 nmol and a maximum effect at 450 nmol. The slopes of the dose-response curves for all three compounds were linear and parallel, with statistically different potencies. The potencies for each compound were identical by all three methods of evaluation. Therefore, we conclude that PAF is a potential mediator in hypersensitivity reaction in the guinea pig conjunctiva, and that its effect is similar to but much more potent than that of histamine or ethanol. Since ethanol alone has a significant effect on vascular permeability, studies on PAF effects using control solutions without ethanol may be difficult to interpret.