Superoxide Dismutase Attenuates Effects of Platelet-Activating Factor on Gastric Microcirculation

This study examined the effect of Cu-Zn superoxide dismutase (SOD) on platelet-activating factor (PAF). induced alterations of the gastric microcirculation. 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 n M, n = 6) alone and with SOD (10 U/ml, n = 5). PAF produced dose-related increases in vascular resistance and filtration. SOD pretreatment attenuated changes in these measurements in response to 9 and 38 n M PAF. PAF also produced dose-related increases in the difference between arterial and venous neutrophil counts across the gastric segment. SOD significantly reduced this neutrophil flux at 0.5, 2, 9, and 38 n M PAF. Our results suggest that PAF causes both mucosal ischemia due to increased vascular resistance and microvascular injury as evidenced by increased filtration, as well as enhanced neutrophil adhesion to the microvasculature. The protective effects of SOD suggest that these responses to PAF involve the generation of oxygen-derived free radicals. In addition, these responses to PAF appear to be dependent upon circulating neutrophils.