ATTENUATION OF ENDOTOXIN-INDUCED INTESTINAL MICROCIRCULATORY DAMAGE BY EICOSAPENTANOIC ACID

The major objective of this study is to investigate whether oral admin istration of eicosapentanoic acid (EPA) has any preventive effect on e ndotoxin-induced microcirculatory damage of rat small intestine. EPA i n a daily dose of 300 mg/kg was orally given to male Wistar rats for 3 wk. Submucosal microvessels of the ileum were observed by intravital microscopy equipped with a high-speed video camera system after the in tra-arterial infusion of endotoxin at a dose of 2 mg.kg-1.h-1. The num ber of sticking leukocytes was significantly increased at 30 min after the treatment of endotoxin especially along the smaller branch of int estinal venules. It reached the maximal plateau at 45 min after treatm ent. The pretreatment of EPA significantly attenuated the increase in sticking leukocytes induced by endotoxin. A platelet-activating factor (PAF) antagonist 2-[N-acetyl-N-(2-methoxy-3-octadecylcarbamoyloxy pro poxycarbonyl) aminomethyl]-1-ethylpyridinium chloride (CV-6209) signif icantly prevented the increased leukocyte sticking to the same extent as EPA treatment. Thirty minutes after endotoxin infusion, red blood c ell (RBC) velocity was significantly decreased in both arterioles and venules. RBC velocity appeared to be continuously decreased thereafter and reached its minimum value at approximately 60 min. EPA treatment was revealed to prevent the decrease in RBC velocity of microvessels i nduced by endotoxin. CV-6209 also significantly attenuated the decreas ed RBC velocity. The remarkable elevation of PAF content in the ileal mucosa as observed by endotoxin infusion was also significantly attenu ated by administration of EPA. EPA is considered to exert its preventi ve effect on endotoxin-induced microcirculatory damage of the small in testine especially through the attenuation of leukocyte accumulation a nd overproduction of PAF.