SUPEROXIDE-DISMUTASE ATTENUATES EFFECTS OF PLATELET-ACTIVATING-FACTORON GASTRIC MICROCIRCULATION

This study examined the effect of Cu-Zn superoxide dismutase (SOD) on platelet-activating factor (PAF)induced alterations of the gastric mic rocirculation. In separate experiments using an ex vivo canine gastric segment, changes in vascular resistance, filtration, and circulating neutrophil counts were measured during intra-arterial infusion of PAF (0.12 to 150 nM = 6) alone and with SOD (10 U/ml, n = 5). PAF produced dose-related increases in vascular resistance and filtration, SOD pre treatment attenuated changes in these measurements in response to 9 an d 38 nM PAF. PAF also produced dose-related increases in the differenc e between arterial and venous neutrophil counts across the gastric seg ment. SOD significantly reduced this neutrophil flux at 0.5, 2, 9, and 38 nM PAF. Our results suggest that PAF causes both mucosal ischemia due to increased vascular resistance and microvascular injury as evide nced by increased filtration, as well as enhanced neutrophil adhesion to the microvasculature. The protective effects of SOD suggest that th ese responses to PAF involve the generation of oxygen-derived free rad icals. In addition, these responses to PAF appear to be dependent upon circulating neutrophils. (C) 1995 Academic Press, Inc.