Altered release of prostaglandins contributes to hypoxic/ischemic impairment of NOC/oFQ cerebrovasodilation.

Abstract

This study was designed to determine if altered release of prostaglandins contributes to impaired pial artery dilation to the newly described opioid, nociceptin/orphanin FQ (NOC/oFQ), following hypoxia/ischemia in newborn pigs equipped with a closed cranial window. Global cerebral ischemia (20 min) was induced via elevation of intracranial pressure, while hypoxia (10 min) decreased P(O(2)) to 35+/-3 mmHg with unchanged P(CO(2)). NOC/oFQ (10(-8) and 10(-6) M) modestly increased cerebrospinal fluid (CSF) 6-Keto PGF(1alpha) and TXB(2), the stable breakdown products of PGI(2) and TXA(2), in sham animals (1199+/-39 to 1704+/-104 and 299+/-9 to 409+/-12 pg/ml for control and 10(-6) M NOC/oFQ 6-Keto PGF(1alpha) and TXB(2), respectively). In 1 h post ischemia/reperfusion (I+R) animals, basal levels of 6-Keto PGF(1alpha) and TXB(2) were elevated. NOC/oFQ-stimulated release of 6-Keto PGF(1alpha) was blocked while such release of TXB(2) was enhanced (526+/-15 to 822+/-36 pg/ml for control and 10(-6) M NOC/oFQ CSF TXB(2)). Similar, though more pronounced, changes were observed in hypoxia/ischemia/reperfusion (H+I+R) animals. Pretreatment with indomethacin (5 mg/kg i.v.) or SQ 29,548 (10(-4) M), cyclooxygenase and PGH(2)/TXA(2) receptor antagonists, partially restored attenuated NOC/oFQ pial artery dilation 1 h after I+R (9+/-1 and 18+/-1 vs. 3+/-1 and 6+/-1 vs. 8+/-1 and 13+/-1% for 10(-8) and 10(-6) M NOC/oFQ in sham, I+R, and I+R - SQ 29,548 pretreated animals). In contrast, NOC/oFQ-induced vasodilation was reversed to vasoconstriction in H+I+R animals and indomethacin or SQ 29,548 similarly partially restored such pial vasodilation. These data indicate that altered stimulated prostaglandin release contributes to hypoxic/ischemic impairment of NOC/oFQ-mediated pial artery dilation.

• Authors: W M Armstead
• Journal: Brain research (Brain Res) Vol. 859 Issue 1 Pg. 104-12 (Mar 17 2000) ISSN: 0006-8993 [Print] Netherlands
• PMID: 10720619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Opioid Peptides
• Prostaglandins
• Vasodilator Agents
• nociceptin

Topics

• Animals
• Animals, Newborn
• Cerebral Arteries (drug effects, metabolism, physiopathology)
• Cerebrovascular Circulation (drug effects, physiology)
• Female
• Hypoxia-Ischemia, Brain (drug therapy, etiology, physiopathology)
• Male
• Opioid Peptides (metabolism, pharmacology)
• Pia Mater (blood supply, metabolism)
• Prostaglandins (metabolism)
• Reperfusion Injury (physiopathology)
• Swine
• Vasodilation (physiology)
• Vasodilator Agents (metabolism, pharmacology)