Send to

Choose Destination
Med Sci Monit. 2002 Jan;8(1):BR8-BR14.

NOC/oFQ activates PKC and generates superoxide to impair hypotensive cerebrovasodilation after hypoxia/ischemia.

Author information

Departments of Anesthesia and Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.



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.


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.


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).


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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for International Scientific Literature, Ltd.
Loading ...
Support Center