IN-VIVO SPIN-TRAPPING OF NITRIC-OXIDE GENERATED IN THE SMALL-INTESTINE, LIVER, AND KIDNEY DURING THE DEVELOPMENT OF ENDOTOXEMIA - A TIME-COURSE STUDY

Spin trapping of nitric oxide (NO .) in vivo in liver, small intestine , kidney, and plasma of intact rats was accomplished using diethyldith iocarbamate (DETC) administered intraperitoneally. DETC combines with Fe2+ to form (DETC)(2)-Fe and is an excellent trapping agent for nitri c oxide. DETC distribution and uptake by the organs of interest was de termined and the formation of the active trapping agent (DETC)(2)-Fe w as assayed in the various organs and plasma. The capacity of this spin trap to capture NO . in vivo was demonstrated by administering sodium nitroprusside to the animals. The trapping procedure was then used to assess the course of NO . generation during a 6 h period in animals t hat had been treated with endotoxin. The rate of NO . generation/gram tissue was determined during the last 15 min of each time period, The results indicate that induction of nitric oxide generation begins earl iest in the small intestine, then in the liver, and still later in the kidney and plasma. Nitric oxide production was most intense in the li ver and was still increasing at the end of the experiment. Control ani mals receiving the spin trapping agent showed only little or no eviden ce of nitric oxide production except for the small intestine. The resu lts show that induction of NO . generation caused by endotoxin begins at different times in different organs.