RESISTANCE AND EXCHANGE MICROVESSELS ARE MODULATED BY DIFFERENT PAF RECEPTORS

Using several platelet activating factor (PAF) receptor antagonists, we investigated whether a differential receptor sensitivity to PAF exists between the arteriolar and venular segments of the microcirculation. The microvascular bed of the hamster cheek pouch was observed with intravital fluorescent television microscopy. Alterations in arteriolar diameter and in the clearance of fluorescein isothiocyanate-dextran (FITC-Dx 150; mol wt 150,000) were measured in response to PAF. Topical application of 10(-7) M PAF elicits a 10-fold increase in FITC-Dx 150 clearance (mean +/- SE = 9,172 +/- 1,289 nl.2 h-1. g-1) compared with control and vasoconstricts arterioles (20-40-mu-m) to approximately 50% their control diameters. Pretreatment with WEB 2086 (2 mg/kg iv) or SDZ 63-675 (10 mg/kg iv) blocks PAF-induced vasoconstriction and significantly attenuates the clearance of FITC-Dx 150 evoked by PAF, producing mean clearance values of 2,164 +/- 604 and 3,648 +/- 262 nl.2 h-1.g-1 respectively. L-659,989 (2 or 10 mg/kg iv) and SDZ 63-675 (5 mg/kg iv) abolished the vasoconstrictor response but not the postcapillary venular permeability response to PAF. These data suggests the presence of heterogeneous PAF receptors between the pre- and postcapillary segments of the microcirculation.