Platelet-activating factor (PAF-acether) and microcirculation: effect of Lyso-PAF and PAF-antagonists

Topical application of a standard dose of noradrenaline (NA) to the anesthetized rat mesentery evoked a vasoconstrictor response the latency of which was increased in a dose-dependent way by previous addition of PAF-acether or histamine but not by Lyso-PAF. Lyso-PAF, however, blocked the antagonistic effect of PAF-acether to NA, the blockade being equivalent to that observed with PAF-antagonists (BN 52021 or WEB 2086) either injected iv, or applied topically. In contrast, the antagonistic action of histamine towards NA was not affected by Lyso-PAF or PAF-antagonists. Since platelet aggregation and leukocyte accumulation did not occur, PAF-acether appears to interact directly with microvessels to block vasoconstrictor stimuli, an effect antagonized by PAF-antagonists and the metabolite/precursor, Lyso-PAF.