Exaggerated splanchnic PGI2 release following acute hemorrhage is due to new protein synthesis.
The effect of cycloheximide on increased splanchnic prostacyclin release following acute hemorrhage was studied in the rat. Male Sprague-Dawley rats were anesthetized and subjected to acute hemorrhage to 30 mm Hg for 30 min (shock) or sham shock. The superior mesenteric artery was cannulated and removed with its end organ intestine (SV + SI preparation) and perfused in vitro with oxygenated Krebs-Henseleit buffer. Cycloheximide was infused in half of the sham and acute hemorrhage SV + SI preparations at 50 micrograms/ml. Venous effluent from all groups were analyzed for prostanoid release by radioimmunoassay. The SV + SI released 10-fold more 6-keto-prostaglandin (PG) F1 alpha than PGE2 and thromboxane. Acute hemorrhage increased SV + SI release of 6-keto-PGF1 alpha 3-fold compared to sham. Cycloheximide abolished the increased 6-keto-PGF1 alpha following acute hemorrhage but not the basal release in the sham group. Indomethacin decreased PG synthesis in all groups by 90%. Sham PG release was dependent on a stable pool of cyclooxygenase with a long half-life and was not affected by cycloheximide treatment. Acute hemorrhage stimulated a rapid induction of enzymes (cyclooxygenase, prostacyclin synthase) responsible for prostacyclin synthesis and release which were dependent on de novo protein synthesis.
Myers
S I
SI
Department of Surgery, University of Texas Southwestern Medical School, Dallas.
Hernandez
R
R
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D006470:Hemorrhage / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation; D013929:Thromboxane B2 / Q000378:metabolism
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003513:Cycloheximide; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin