Background: Previous studies have observed that hypotensive pial artery dilation 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 the rat while the opioid nociceptin/orphanin FQ (NOC/oFQ) generated O-2 via activation of protein kinase C in the piglet. This study determined the contribution of NOC/oFQ, PKC activation and O-2 generation in hypoxic ischemic hypotensive cerebrovasodilation impairment.
Material/methods: Anesthetized newborn pigs equipped with a closed cranial window were used. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia, via inhalation of nitrogen, decreased PO2 to 34I3 mmHg.
Results: Topical NOC/oFQ (10-10M), the CSF concentration following hypoxia/ischemia, had no effect on pial artery diameter by itself but attenuated hypotension (mean arterial blood pressure decrease of 44I2%) induced pial artery dilation (33I1 vs 19I2%). Coadministration of the PKC inhibitor chelerythrine (10-7M) or the O-2 scavenger polyethylene glycol superoxide dismutase and catalase (SODCAT) with NOC/oFQ (10-10M) partially prevented hypotensive pial dilation impairment (34I2 vs 28I1% for SODCAT). Hypotensive pial artery dilation was blunted 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 contributes to hypoxia/ischemia impairment of hypotensive pial artery dilation. These data suggest that NOC/oFQ activates PKC and generates O-2 to impair hypotensive cerebrovasodilation after hypoxia/ischemia.