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Am J Physiol Heart Circ Physiol 278: H477-H483, 2000;
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Vol. 278, Issue 2, H477-H483, February 2000

Relationship between nociceptin/orphanin FQ and cerebral hemodynamics after hypoxia-ischemia in piglets

William M. Armstead

Departments of Anesthesia and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104

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 PO2 to 35 ± 3 mmHg with unchanged PCO2. 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.

newborn; cerebral circulation; opioids


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