NOC/oFQ and NMDA contribute to piglet hypoxic ischemic hypotensive cerebrovasodilation impairment

Previous studies have observed that hypotensive pial artery dilation v,,as blunted after hypoxia-ischemia. In unrelated studies. the opioid nociceptiri/orphanin FQ (NOC/oFQ) was observed to contribute to hypoxic ischemic impairment of N-methyl-D-aspartate (NMDA)-induced pial dilation. This study determined the contribution of NOC/oFQ and NMDA to hypoxic ischemic hypotensive cerebrovasodilation impairment in newborn pigs equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased Po-2 to 33 +/- 3 mm Hg. Topical NOC/oFQ (10(-10) M). the cerebrospinal fluid concentration after hypoxia-ischemia. had no effect on pial artery diameter by itself but attenuated hypotension (mean arterial blood pressure decrease of 44 +/- 2%) -induced pial artery dilation (35 +/- 2% versus 22 +/- 3%). Hypotensive pial artery dilation was blunted by hypoxia-ischemia. but such dilation was partially protected by pretreatment with the putative NOC/oFQ receptor antagonist. [F/G] NOC/oFQ (1-13) NH2 (10(-6) M 29 2%, sham controls 7 2% hypoxia-ischemia: and 13 +/- 2%. hypoxia-ischemia and [F/G] NOC/oFQ (1-13) NH2). Coadministration of the NMDA antagonist MK801 (10(-5) M) with NOC/oFQ(10 (10) M) partially prevented hypotensive pial dilation impairment. Similarly, pretreatment with MK801 partially protected hypoxic ischemia impairment of hypotensive pial dilation (35 +/- 2%, sham control: 7 +/- 1%. hypoxia-ischemia: 22 +/- 2%. hypoxia-ischemia + MK801). These data show that NOC/oFQ and NMDA contribute to hypoxic ischemic hypotensive cerebrovasodilation impairment, These data suggest that NOC/oFQ modulation of NMDA vascular activity also contributes to such hypotensive impairment.