Oxyhemoglobin-induced expression of R-type Ca2+ channels in cerebral arteries

被引:42
作者
Link, Timothy E. [2 ]
Murakami, Kentaro [1 ]
Beem-Miller, Micah [1 ]
Tranmer, Bruce I. [2 ]
Wellman, George C. [1 ,2 ]
机构
[1] Univ Vermont, Coll Med, Dept Pharmacol, Burlington, VT 05405 USA
[2] Univ Vermont, Coll Med, Dept Surg, Div Neurosurg, Burlington, VT 05405 USA
关键词
calcium channels; cerebral arteries; subarachnoid hemorrhage; vasospasm; vascular smooth muscle;
D O I
10.1161/STROKEAHA.107.508754
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose - Cerebral vasospasm after subarachnoid hemorrhage ( SAH) is a major contributor to mortality and morbidity after aneurysm rupture. Recently, R-type voltage-dependent Ca2+ channel ( VDCC) expression has been associated with increased cerebral artery constriction in a rabbit model of SAH. The goal of the present study was to examine whether the blood component oxyhemoglobin ( oxyHb) can mimic the ability of SAH to cause R-type VDCC expression in the cerebral vasculature. Methods - Rabbit cerebral arteries were organ cultured in serum-free media for up to 5 days in the presence or absence of purified oxyHb ( 10 mu mol/L). Diameter changes in response to diltiazem, (L-type VDCC antagonist) and SNX-482 (R-type VDCC antagonist) were recorded at day 1, 3, or 5 in arteries constricted by elevated extracellular potassium. RT-PCR was performed on RNA extracted from arteries cultured for 5 days ( +/- oxyHb) to assess VDCC expression. Results - After 5 days, oxyHb-treated arteries were less sensitive and partially resistant to diltiazem compared to similar arteries organ cultured in the absence of oxyHb. Further, SNX-482 dilated arteries organ cultured for 5 days in the presence, but not in the absence, of oxyHb. RT-PCR revealed that oxyHb treated arteries expressed R-type VDCCs ( Ca-V 2.3) in addition to L-type VDCCs (Ca-V 1.2), whereas untreated arteries expressed only Ca-V 1.2. Conclusions - These results demonstrate that oxyhemoglobin exposure for 5 days induces the expression of CaV 2.3 in cerebral arteries. We propose that oxyhemoglobin contributes to enhanced cerebral artery constriction after SAH via the emergence of R-type VDCCs.
引用
收藏
页码:2122 / 2128
页数:7
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