title: Age-dependent NOC/oFQ contribution to impaired hypotensive cerebral hemodynamics after brain injury.
abstract: Previous studies have observed that the newly described opioid, nociceptin/orphanin FQ (NOC/oFQ), contributed to age dependent reductions in cerebral blood flow (CBF) and pial artery diameter after fluid percussion brain injury (FPI). Unrelated studies have noted a similar age dependency in impaired hypotensive cerebral autoregulation after FPI. This study was designed to compare the role of NOC/oFQ in impaired hypotensive cerebral autoregulation after FPI in newborn and juvenile pigs equipped with a closed cranial window. Ten minutes of hemorrhagic hypotension (10-15 mL blood/kg) decreased mean arterial blood pressure uniformly in both groups ( approximately 44%). In the newborn, hypotensive pial artery dilation was blunted within 1 h of FPI but partially protected by pretreatment with the NOC/oFQ antagonist, [F/G] NOC/oFQ (1-13) NH(2) (1 mg/kg, i.v.) (34 +/- 1 vs. 8 +/- 1 vs. 20 +/- 2% for sham control, FPI, and FPI-[F/G] NOC/oFQ (1-13) NH(2), respectively). CBF was reduced during normotension by FPI, further reduced by hypotension, but both were partially protected by this antagonist in the newborn (63 +/- 4, 34 +/- 2, and 20 +/- 2 vs. 65 +/- 4, 47 +/- 2, and 29 +/- 2 mL/min.100 g for normotension, normotension-FPI and hypotension-FPI in the absence and presence of [F/G] NOC/oFQ (1-13) NH(2), respectively). In contrast, blunted hypotensive pial artery dilation was protected significantly less by this NOC/oFQ antagonist in the juvenile (32 +/- 2 vs. 7 +/- 2 vs. 13 +/- 2% for sham control, FPI and FPI-NOC/oFQ antagonist, respectively). Similarly, [F/G] NOC/oFQ (1-13) NH(2) had less protective effect on normotensive and hypotensive CBF values post FPI in the juvenile. These data indicate that NOC/oFQ contributes to impaired hypotensive cerebral hemodynamics following brain injury in an age-dependent manner.
authors.affiliation: Department of Anesthesia and Pharmacology, University of Pennsylvania, Philadelphia 19104, USA. armsteaw@mail.med.upenn.edu
authors.forename: William M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D007022:Hypotension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D013552:Swine; D014664:Vasodilation / Q000502:physiology; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D010446:Peptide Fragments; D000097629:Nociceptin; C439964:nociceptin (1-13) amide