INCREASED SPLANCHNIC PROSTACYCLIN SYNTHASE AND CYCLOOXYGENASE CONTENTAND ACTIVITY DURING ISCHEMIA IS DUE TO NEW-PROTEIN SYNTHESIS

Background. This study examines the hypothesis that the exaggerated sp lanchnic release of prostacyclin is due to new synthesis of both cyclo oxygenase and prostacyclin synthase (PS) in the ileum muscularis/seros a. Methods. Sprague-Dawley rats were anesthetized and subjected to acu te hemorrhage to 30 mm Hg for 30 minutes (shock) or sham shock. The su perior mesenteric artery (SMA) was cannulated and removed with its end -organ intestine and perfused in vitro with Krebs-Henseleit buffer wit h and without cycloheximide (50 mu g/ml) or indomethacin (20 mu g./ml) . Venous effluent was analyzed for eicosanoids by radioimmunoassay. Th e SMA, aorta and ileal mucosa, and muscularis/serosa were analyzed for PS and cyclooxygenase content by immunoblot analysis. Results. The sh am splanchnic bed released threefold more 6-keto-PFG(1 alpha) than pro staglandin E(2) and thromboxane. Acute ischemia increased splanchnic r elease of 6-keto-PGF(1 alpha) threefold compared with sham, which was abolished by cycloheximide or indomethacin treatment. Acute ischemia i ncreased content of PS and cyclooxygenase in the ileal muscularis/sero sa twofold and PS in the aorta and SMA by 50%. Conclusions. Acute isch emia increased release of 6-keto-PGF(1 alpha), which was dependent on new protein synthesis. The immunoblot data suggest that the location o f the increased enzymes responsible for increased 6-keto-PGF(1 alpha) release is the ileal muscularis/serosa and in the aorta and SMA.