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 nM, 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 nM 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 nM 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.
Department of Surgery, University of Kansas Medical Center, Kansas City 66160, USA.
J R
JR
Schwappach
J G
JG
Wood
L Y
LY
Cheung
D000818:Animals; D001773:Blood Cells / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007958:Leukocyte Count; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D013270:Stomach / Q000098:blood supply*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D010972:Platelet Activating Factor; D013482:Superoxide Dismutase