Increased splanchnic prostacyclin synthase and cyclooxygenase content and activity during ischemia is due to new protein synthesis.
BACKGROUND
This study examines the hypothesis that the exaggerated splanchnic release of prostacyclin is due to new synthesis of both cyclooxygenase and prostacyclin synthase (PS) in the ileum muscularis/serosa.


METHODS
Sprague-Dawley rats were anesthetized and subjected to acute hemorrhage to 30 mm Hg for 30 minutes (shock) or sham shock. The superior mesenteric artery (SMA) was cannulated and removed with its end-organ intestine and perfused in vitro with Krebs-Henseleit buffer with and without cycloheximide (50 micrograms/ml) or indomethacin (20 micrograms/ml). Venous effluent was analyzed for eicosanoids by radioimmunoassay. The SMA, aorta and ileal mucosa, and muscularis/serosa were analyzed for PS and cyclooxygenase content by immunoblot analysis.


RESULTS
The sham splanchnic bed released threefold more 6-keto-PGF1 alpha than prostaglandin E2 and thromboxane. Acute ischemia increased splanchnic release of 6-keto-PGF1 alpha threefold compared with sham, which was abolished by cycloheximide or indomethacin treatment. Acute ischemia increased content of PS and cyclooxygenase in the ileal muscularis/serosa twofold and PS in the aorta and SMA by 50%.


CONCLUSIONS
Acute ischemia increased release of 6-keto-PGF1 alpha, which was dependent on new protein synthesis. The immunoblot data suggest that the location of the increased enzymes responsible for increased 6-keto-PGF1 alpha release is the ileal muscularis/serosa and in the aorta and SMA.
Myers
S I
SI
Department of Surgery, University of Texas Southwestern Medical School, Dallas.
Evans
C T
CT
Hernandez
R
R
Bartula
L
L
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D015777:Eicosanoids / Q000096:biosynthesis; D019746:Intramolecular Oxidoreductases; D007511:Ischemia / Q000201:enzymology*; D007535:Isomerases / Q000096:biosynthesis*; D008643:Mesentery / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015777:Eicosanoids; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase