Platelet-activating factor modulates microvascular dynamics through phospholipase C in the hamster cheek pouch

We studied the interactions between platelet-activating factor (PAF) and ph ospholipase C (PLC) in the modulation of microvascular responses in the ham ster cheek pouch using intravital microscopy and computer-assisted image an alysis. Changes in arteriolar diameter and in integrated optical intensity (IOI, an index of vascular permeability) were measured. Fluorescein-isothio cyanate-labeled dextran 150 (FITC-Dx 150) served as a tracer for macromolec ular transport. 2-Nitro-4-carboxyphenyl N,N-diphenylcarbamate (NCDC) and 1- (6-((17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2 ,5,-dione (U-73122), two PLC inhibitors, were applied topically in separate experiments. PAF at 10(-7) M elevated IOI from baseline to a mean a SEM va lue of 70.7 +/- 8.9 units. Pretreatment with 10(-4) and 10(-5) M NCDC and w ith U-73122 at 10(-5) and 10(-6) M attenuated the maximal increment in mean IOI (+/-SEM) induced by PAF at 10(-7) M to mean +/- SEM values of 30.6 +/- 6.5, 39.3 +/- 6.0, 12.1 +/- 4.8, and 41.5 +/- 6.0, respectively. The simul taneous vasoconstrictor action of 10(-7) M PAF was expressed as the experim ental-to-baseline ratio, with the baseline diameter adjusted to a value of 1. PAF constricted the arterioles to a mean +/- SEM ratio of 0.30 +/- 0.07. Pretreatment with the PLC inhibitors NCDC at 10(-4) and 10(-5) M NCDC and with U-73122 at 10(-5) and 10(-6) M attenuated 10(-7) M PAF-induced vasocon striction to mean +/- SEM diameter ratios of 0.55 +/- 0.05, 0.48 +/- 0.06, 0.55 +/- 0.08, and 0.58 +/- 0.06, respectively. Our results demonstrate tha t PLC is an element of the biochemical pathway involved in PAF modulation o f microvascular permeability and in PAF modulation of arteriolar diameter. (C) 2000 Academic Press.