BACKGROUND: Previous studies have observed that hypotensive pial arterydilation was blunted following global cerebral ischemia in the piglet. In unrelated studies, superoxide(O-2) contributed to impaired hypotensive cerebrovasodilation following traumatic brain injury in therat while the opioid nociceptin/orphanin FQ (NOC/oFQ) generated O-2 via activation of protein kinaseC in the piglet. This study determined the contribution of NOC/oFQ, PKC activation and O-2 generationin hypoxic ischemic hypotensive cerebrovasodilation impairment.Material/Methods: Anesthetized newbornpigs equipped with a closed cranial window were used. Global cerebral ischemia was produced via elevatedintracranial pressure. Hypoxia, via inhalation of nitrogen, decreased PO2 to 34I3 mmHg. RESULTS: TopicalNOC/oFQ (10-10M), the CSF concentration following hypoxia/ischemia, had no effect on pial artery diameterby itself but attenuated hypotension (mean arterial blood pressure decrease of 44I2%) induced pial arterydilation (33I1 vs 19I2%). Coadministration of the PKC inhibitor chelerythrine (10-7M) or the O-2 scavengerpolyethylene glycol superoxide dismutase and catalase (SODCAT) with NOC/oFQ (10-10M) partially preventedhypotensive pial dilation impairment (34I2 vs 28I1% for SODCAT). Hypotensive pial artery dilation wasblunted by hypoxia/ischemia but such dilation was partially protected by the NOC/oFQ receptor antagonist[F/G] NOC/oFQ (1-13) NH2 (10-6M), chelerythine or SODCAT (34I1 vs 7I2 vs 21I2% for sham, H/I and H/I+ SODCAT, respectively). CONCLUSIONS: These data show that PKC activation and generation of O-2 contributesto hypoxia/ischemia impairment of hypotensive pial artery dilation. These data suggest that NOC/oFQ activatesPKC and generates O-2 to impair hypotensive cerebrovasodilation after hypoxia/ischemia.

Keywords: Animals, Newborn, Anoxia, Arteries, Ischemia, Models, Biological, Opioid Peptides, Oxygen, Pressure, Protein Kinase C, Research Support, Non-U.S. Gov, Research Support, U.S. Gov, Superoxides, Swine, Time Factors, Vasodilation