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

被引:21
作者
Armstead, WM
机构
[1] Univ Penn, Dept Anesthesia, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2000年 / 279卷 / 05期
关键词
newborn; cerebral circulation; opioids; excitatory amino acids;
D O I
10.1152/ajpheart.2000.279.5.H2188
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (approximate to 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 (approximate to 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)-NH2 (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.
引用
收藏
页码:H2188 / H2195
页数:8
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