NOC/oFQ contributes to age-dependent impairment of NMDA-induced cerebrovasodilation after brain injury.

Abstract

This study characterized the effects of fluid percussion brain injury (FPI) on N-methyl-D-aspartate (NMDA)-induced vasodilation and determined the role of nociceptin/orphanin FQ (NOC/oFQ) in such changes as a function of age and time postinsult. FPI elevated cerebrospinal fluid (CSF) NOC/oFQ from 70 +/- 3 to 444 +/- 56 pg/ml ( approximately 10(-10) M) within 1 h and to 1,931 +/- 112 pg/ml within 8 h, whereas values returned to control levels within 168 h in the newborn pig. In contrast, FPI elevated CSF NOC/oFQ from 77 +/- 4 to 202 +/- 16 pg/ml within 1 h and values returned to control levels within 8 h in the juvenile pig. Topical NOC/oFQ (10(-10) M) had no effect on pial artery diameter but attenuated NMDA (10(-8), 10(-6) M)-induced dilation (9 +/- 1 and 16 +/- 1 vs. 5 +/- 1 and 10 +/- 1%) in both age groups. In the newborn, NMDA-induced pial artery dilation was reversed to vasoconstriction within 1 h post-FPI and responses remained impaired for 72 h, but such vasoconstriction was attenuated by pretreatment with [F/G]NOC/oFQ(1-13)-NH(2) (10(-6) M, 1 mg/kg iv), an NOC/oFQ antagonist (9 +/- 1 and 16 +/- 1 vs. -7 +/- 1 and -12 +/- 1 vs -2 +/- 1 and -3 +/- 1% for control, FPI, and FPI pretreated with the NOC/oFQ antagonist). In contrast, in the juvenile, NMDA-induced vasodilation was only attenuated within 1 h post-FPI and returned to control within 8 h. Such dilation was also partially restored by the NOC/oFQ antagonist. These data indicate that NOC/oFQ contributes to impaired NMDA pial artery dilation after FPI. These data suggest that the greater NOC/oFQ release in the newborn versus the juvenile may contribute to age-related differences in FPI effects on excitatory amino acid-induced pial dilation.

• Authors: W M Armstead
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 279 Issue 5 Pg. H2188-95 (Nov 2000) ISSN: 0363-6135 [Print] United States
• PMID: 11045952 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• (F-G)NOC oFQ(1-13)-NH2
• Excitatory Amino Acids
• Narcotic Antagonists
• Opioid Peptides
• Peptide Fragments
• Receptors, Opioid
• Glutamic Acid
• N-Methylaspartate
• nociceptin
• Nociceptin Receptor

Topics

• Aging (drug effects, metabolism)
• Animals
• Animals, Newborn
• Arterioles (drug effects)
• Blood Pressure (drug effects)
• Brain Injuries (metabolism)
• Cerebrovascular Circulation (drug effects)
• Disease Models, Animal
• Excitatory Amino Acids (metabolism, pharmacology)
• Female
• Glutamic Acid (metabolism, pharmacology)
• Male
• N-Methylaspartate (metabolism, pharmacology)
• Narcotic Antagonists
• Opioid Peptides (cerebrospinal fluid, metabolism, pharmacology)
• Peptide Fragments (pharmacology)
• Pia Mater (blood supply, drug effects)
• Receptors, Opioid
• Swine
• Vasoconstriction (drug effects)
• Vasodilation (drug effects)
• Wounds, Nonpenetrating
• Nociceptin Receptor