Nociceptin/Orphanin FQ Alters Prostaglandin Cerebrovascular Action following Brain Injury

Previous studies have observed that fluid percussion brain injury (FPI) elevated the CSF concentration of the opioid nociceptin/orphanin FQ (NOC/oFQ). In separate studies, FPI impaired pial artery dilation to the prostaglandins PGI2 and PGE2. This study was designed to investigate the following: (1) role of NOC/oFQ in impaired dilation to PGI2 and PGE2, (2) the effects of FPI on vasoconstriction to the TXA2 mimic U46619 and PGF2α, and (3) the role of NOC/oFQ in such FPI induced effects on U46619 and PGF2α. Lateral FPI was induced in newborn pigs equipped with a closed cranial window. PGI2 (1, 10, 100 ng/ml) vasodilation was blunted by FPI and fully restored by the NOC/oFQ antagonist, [F/G] NOC/oFQ (1-13) NH2 (10-6M) (9 ± 1, 13 ± 1, and 19 ± 1 vs. 2 ± 1, 4 ± 1, and 5 + 1 vs 7 ± 1, 12 ± 2, and 17 ± 3% for control, FPI, and FPI + [F/G] NOC/oFQ (1-13) NH2, respectively). Similar effects were observed for PGE2. In contrast, U46619 (1, 10 ng/ml) induced vasoconstriction was potentiated by FPI but returned to th...