Time course of release in vivo of PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and TxB2 into the brain extracellular space after 15 min of complete global ischemia in the presence and absence of cyclooxygenase inhibition.
The time-dependent release of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), thromboxane (Tx) B2, and 6-keto-PGF1 alpha (6-keto) from brain was measured before, during, and after a 15-min interval of total ischemia (four-vessel occlusion) in halothane-anesthetized cats using the technique of cerebroventricular perfusion. Resting levels of PGE2, PGF2 alpha, 6-keto, and Tx were: 253 +/- 75, 953 +/- 300, 650 +/- 200, and 550 +/- 170 pg/ml, respectively. During the 15-min ischemia, all prostanoids rose significantly, yet the highest levels were not observed until the first 15-60 min of the reflow at which time levels of PGE2, PGF2 alpha, 6-keto, and Tx, as compared with the preischemic baseline, rose approximately 8, 3.4, 3, and 55-fold, respectively. Significantly, although all prostanoids showed increases relative to baseline, the ratios of PGF2 alpha/6-keto and PGE2/6-keto remained stable throughout the experiment in both groups of animals. In contrast, the Tx/6-keto ratio rose from approximately 1 to approximately 30 during the 60 min after reflow in untreated cats. Treatment with zomepirac sodium (5 mg/kg, i.v.), a cyclooxygenase inhibitor, resulted in highly significant reductions in the levels of all prostanoids during the preischemic period. In zomepirac sodium-treated animals, there were also highly significant reductions in the prostanoid response to ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000201:enzymology / Q000378:metabolism*; D002415:Cats; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism; D014046:Tolmetin / Q000031:analogs & derivatives / Q000494:pharmacology
D005343:Fibrinolytic Agents; D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C020549:zomepirac; D015237:Dinoprost; D014046:Tolmetin; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone