Affiliation:
1. Departments of Anesthesia and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
Abstract
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[Formula: see text] to 35 ± 3 mmHg with unchanged[Formula: see text]. 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 ⋅ min− 1 ⋅ 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)-NH2 (1 mg/kg iv), an NOC/oFQ antagonist, however, CBF only fell to 43 ± 3 ml ⋅ min− 1 ⋅ 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.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
21 articles.
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