Brain injury impairs prostaglandin cerebrovasodilation

被引:27
作者
Armstead, WM
机构
[1] Childrens Hosp Philadelphia, Dept Anesthesia, Philadelphia, PA 19104 USA
[2] Childrens Hosp Philadelphia, Dept Pharmacol, Philadelphia, PA 19104 USA
[3] Univ Penn, Dept Anesthesia, Philadelphia, PA 19104 USA
[4] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA
关键词
cerebral circulation; cyclic nucleotides; newborn; K(+) channel;
D O I
10.1089/neu.1998.15.721
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Previous studies have observed that ATP- and calcium-sensitive K(+) (K(ATP) and K(ca)) channel function is impaired after fluid percussion brain injury (FPI). The present study was designed to characterize the effect of FPI on prostaglandin (PG)E(2) and I(2) pial artery dilation and the role of activation of these K(+) channels in that dilation in newborn pigs equipped with a closed cranial window, FPI of moderate severity (1.9-2.1 atm) was produced by using a pendulum to strike a piston on a saline-filled cylinder that was fluid coupled to the brain via a hollow screw inserted through the cranium. PGE(2) vasodilation was blunted by FPI (9 +/- 1%, 13 +/- 1%, and 19 +/- 1% vs. 2 +/- 1%, 5 +/- 1%, and 9 +/- 1%, for 1, 10, and 100 ng/ml PGE(2) before and after FPI, respectively). PGE(2) dilation was associated with increased CSF cGMP and cAMP concentration and such changes in cyclic nucleotides were blunted by FPI (448 +/- 10 and 793 +/- 38 vs, 316 +/- 11 and 403 +/- 27 fmol/ml for control and PGE(2) induced change in cGMP before and after FPI, respectively), PGI(2)-induced dilation and associated changes in CSF cyclic nucleotide concentration were similarly blunted by FPI. PGE(2) dilation was attenuated by either glibenclamide or iberiotoxin, K(ATP) and K(ca) channel antagonists, and coadministration of both K+ channel antagonists further decremented the dilator response (9 +/- 1%, 14 +/- 1%, and 21 +/- 1%; vs, 4 +/- 1%, 7 +/- 1%, and 12 +/- 1%; vs. 2 +/- 1%, 4 +/- 1%, and 7 +/- 1%, for 1, 10, and 100 ng/ml PGE(2) during control, after glibenclamide, and after combined glibenclamide and iberiotoxin, respectively). Glibenclamide and iberiotoxin had similar effects on PGI(2) dilation. These data show that prostaglandin dilation is attenuated after FPI. These data also show that prostaglandin dilation is dependent on activation of both K(ATP) and K(ca) channels. Further, these data suggest that attenuated prostaglandin dilation following FPI results from diminished prostaglandin-associated elevation in cyclic nucleotide concentration and impaired K(ATP) and K(ca) channel function.
引用
收藏
页码:721 / 729
页数:9
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