title: Nociceptin/orphanin FQ contributes to hypoxic/ischemic impairment of hypercapnic cerebrovasodilation.
abstract: Previous studies in piglets show that hypercapnic pial artery dilation was blunted following cerebral ischemia. Unrelated studies show that the newly described opioid nociceptin orphanin FQ (NOC/oFQ) is released into cerebrospinal fluid and contributes to altered cerebral hemodynamics following hypoxia/ischemia. This study was designed to determine the contribution of NOC/oFQ to hypoxic/ischemic impairment of hypercapnic pial dilation in piglets equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased P(O2) to 34 +/- 3 mmHg. Topical NOC/oFQ (10(-10) M), the CSF concentration following hypoxia/ischemia, had no effect on pial artery diameter by itself but attenuated hypercapnia P(CO2) of (73 +/- 2 mmHg)-induced pial artery dilation (28 +/- 2 vs. 19 +/- 2%). Hypercapnia 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) NH(2) (10(-6) M), (25 +/- 1, sham control; 4 +/- 1, hypoxia/ischemia; and 12 +/- 3%, hypoxia/ischemia + [F/G] NOC/oFQ (1-13) NH(2), respectively). These data suggest that NOC/oFQ release contributes to impaired hypercapnia-induced cerebrovasodilation following hypoxia/ischemia.
authors.affiliation: Department of Anesthesia, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jagolino
authors.forename: W M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001784:Blood Gas Analysis; D001794:Blood Pressure; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006935:Hypercapnia / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D008297:Male; D018847:Opioid Peptides / Q000378:metabolism*; D010841:Pia Mater / Q000098:blood supply; D013552:Swine; D014664:Vasodilation / Q000502:physiology*; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D000097629:Nociceptin