Modulation of Microvascular Hydraulic Permeability by Platelet-Activating Factor

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Abstract
Background Platelet-activating factor (PAF) is a modulator of the inflammatory response to shock. Edema formation and intravascular fluid loss have been associated with PAF. The increase in microvessel permeability caused by PAF may be related to direct endothelial cell activation and leukocyte activation. We hypothesized that PAF increases hydraulic permeability by means of the direct activation of endothelial cells. Methods Hydraulic permeability (Lp) was measured in rat mesenteric venules using the modified Landis micro-occlusion technique. After baseline Lp measurements, paired measures of Lp were obtained during PAF perfusion at doses of 0.1 nmol/L (n = 6), 1.0 nmol/L (n = 6), 10 nmol/L (n = 6), and 50 nmol/L (n = 6). The temporal effects of pulse administration of PAF and repeated exposures to PAF were also assessed. Results Compared with baseline values (Lp = 1.16 ± 0.11), the Lp of the microvessels significantly increased at PAF doses of 0.1 nmol/L (Lp = 1.46 ± 0.1) (p < 0.002), 1 nmol/L (Lp = 2.0 ± 0.11) (p < 0.004), 10 nmol/L (Lp = 4.09 ± 0.09) (p < 0.005), and 50 nmol/L (Lp = 5.13 ± 0.07) (p < 0.0001). All units for Lp are given as ± SE × 10 −7 cm s−1 · cm H2O−1. Conclusion PAF increased microvessel permeability in a dose-dependent manner. The permeability-increasing effect of PAF was transient even with continuous endothelial exposure to PAF. This study emphasizes the ability of PAF to directly modulate microvascular permeability and increase venular permeability.