Relationship between nociceptin/orphanin FQ and cerebral hemodynamics after hypoxia-ischemia in piglets.
This study was designed to characterize the role of the newly described endogenous opioid nociceptin/orphanin FQ (NOC/oFQ) in reduced cerebral blood flow (CBF) observed after ischemia-reperfusion (I/R) and combined hypoxia and ischemia-reperfusion (H-I/R), as a function of time after onset of reperfusion in newborn pigs equipped with a closed cranial window. Global cerebral ischemia (20 min) was induced via elevation of intracranial pressure, whereas hypoxia (10 min) decreased PO(2) to 35 +/- 3 mmHg with unchanged PCO(2). I/R elevated cerebrospinal fluid (CSF) NOC/oFQ from 67 +/- 4 to 266 +/- 29 pg/ml within 1 h, whereas values returned to control level within 4 h of reperfusion. H-I/R elevated CSF NOC/oFQ to 483 +/- 67 pg/ml within 1 h, and such values returned slowly to control level within 12 h of reperfusion. Topical NOC/oFQ (10(-8) M, 10(-6) M)-induced vasodilation was attenuated by I/R and reversed to vasoconstriction by H-I/R at 1 h of reperfusion (control, 9 +/- 1 and 16 +/- 1%; I/R, 3 +/- 1 and 6 +/- 1%; H-I/R, -6 +/- 1 and -11 +/- 1%). Such altered dilation returned to control values within 4 h in I/R animals and within 12 h in H-I/R animals. Blood flow in the cerebrum was reduced from 58 +/- 4 to 33 +/- 2 ml x min(-1) x 100 g(-1) within 1 h and returned to control value within 4 h in I/R animals. In animals pretreated with [F/G]NOC/oFQ(1-13)-NH(2) (1 mg/kg iv), an NOC/oFQ antagonist, however, CBF only fell to 43 +/- 3 ml x min(-1) x 100 g(-1) at 1 h of reperfusion. Similar observations were made in H-I/R animals. These data suggest that an elevated CSF NOC/oFQ concentration and altered vascular responsiveness to this opioid contribute to reductions in CBF observed after either I/R or H-I/R.
Armstead
W M
WM
Departments of Anesthesia and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. armsteaw@mail.med.upenn.edu
D000818:Animals; D000831:Animals, Newborn; D001158:Arteries / Q000503:physiopathology; D002545:Brain Ischemia / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D005260:Female; D006439:Hemodynamics; D000860:Hypoxia / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology*; D008297:Male; D018847:Opioid Peptides / Q000134:cerebrospinal fluid*; D010841:Pia Mater / Q000098:blood supply; D013552:Swine; D000097629:Nociceptin
D018847:Opioid Peptides; D000097629:Nociceptin